Pharmacists' Perceptions of the Economic Value of Compounded Pharmaceuticals: A Comparison of Compounded and Commercial Pharmaceuticals in Select Disease States.

PubMed

Lobb, William B; Wilkin, Noel E; Holmes, Erin R

2015-01-01

Studies have been conducted to assess patient satisfaction with compounded pharmaceuticals and to directly compare compounded pharmaceuticals with their comparable commercial pharmaceuticals. Yet, the economic value of or potential for economic value derived from compounded pharmaceuticals relative to commercial pharmaceuticals is still not known. Therefore, the purpose of this study was to assess and compare compounding and non-compounding pharmacists' perceptions of the economic value of compounded preparations relative to commercial products. In-depth interviews with 10 compounding pharmacists and physicians who prescribe compounded prescription pharmaceutical preparations were conducted to help develop a self-administered questionnaire distributed to 50 compounding and 50 non-compounding pharmacists. Compounding and non-compounding pharmacists' perceptions differed most often in the context of compounded pharmaceuticals for pediatric patients. However, both groups responded with moderate agreement that compounded prescription treatments are more profitable for the pharmacy than commercial prescription treatments in most therapeutic areas. This research sought to understand the perception of pharmacists of areas for potential direct and indirect economic cost savings as a result of compounding. For all items whereby compounding and non-compounding pharmacists' ratings were significantly different, compounding pharmacists more strongly believed that compounding pharmaceuticals offered benefit and vice versa. The differences in ratings that were most common were those that directly compared the economic value of compounding and commercial pharmaceuticals, with compounding pharmacists more strongly agreeing with the potential cost savings associated with compounded pharmaceuticals. Based on these findings, prescription compounds are believed to have a benefit to the health system by those who provide them. Future research should proactively explore the economic benefit of compounded preparations compared to conventionally manufactured products to determine the economic value of compounded pharmaceuticals for patients, pharmacies, physicians, and the healthcare system.

Occurrence and concentrations of pharmaceutical compounds in deep groundwater used for public drinking-water supply in California

USGS Publications Warehouse

Fram, Miranda S.; Belitz, Kenneth

2011-01-01

Pharmaceutical compounds were detected at low concentrations in 2.3% of 1231 samples of groundwater (median depth to top of screened interval in wells = 61 m) used for public drinking-water supply in California. Samples were collected statewide for the California State Water Resources Control Board's Groundwater Ambient Monitoring and Assessment (GAMA) Program. Of 14 pharmaceutical compounds analyzed, 7 were detected at concentrations greater than or equal to method detection limits: acetaminophen (used as an analgesic, detection frequency 0.32%, maximum concentration 1.89 μg/L), caffeine (stimulant, 0.24%, 0.29 μg/L), carbamazepine (mood stabilizer, 1.5%, 0.42 μg/L), codeine (opioid analgesic, 0.16%, 0.214 μg/L), p-xanthine (caffeine metabolite, 0.08%, 0.12 μg/L), sulfamethoxazole (antibiotic, 0.41%, 0.17 μg/L), and trimethoprim (antibiotic, 0.08%, 0.018 μg/L). Detection frequencies of pesticides (33%), volatile organic compounds not including trihalomethanes (23%), and trihalomethanes (28%) in the same 1231 samples were significantly higher. Median detected concentration of pharmaceutical compounds was similar to those of volatile organic compounds, and higher than that of pesticides. Pharmaceutical compounds were detected in 3.3% of the 855 samples containing modern groundwater (tritium activity > 0.2 TU). Pharmaceutical detections were significantly positively correlated with detections of urban-use herbicides and insecticides, detections of volatile organic compounds, and percentage of urban land use around wells. Groundwater from the Los Angeles metropolitan area had higher detection frequencies of pharmaceuticals and other anthropogenic compounds than groundwater from other areas of the state with similar proportions of urban land use. The higher detection frequencies may reflect that groundwater flow systems in Los Angeles area basins are dominated by engineered recharge and intensive groundwater pumping.

The adsorption of pharmaceutically active compounds from aqueous solutions onto activated carbons.

PubMed

Rakić, Vesna; Rac, Vladislav; Krmar, Marija; Otman, Otman; Auroux, Aline

2015-01-23

In this study, the adsorption of pharmaceutically active compounds - salicylic acid, acetylsalicylic acid, atenolol and diclofenac-Na onto activated carbons has been studied. Three different commercial activated carbons, possessing ∼650, 900 or 1500m(2)g(-1) surface areas were used as solid adsorbents. These materials were fully characterized - their textural, surface features and points of zero charge have been determined. The adsorption was studied from aqueous solutions at 303K using batch adsorption experiments and titration microcalorimetry, which was employed in order to obtain the heats evolved as a result of adsorption. The maximal adsorption capacities of investigated solids for all target pharmaceuticals are in the range of 10(-4)molg(-1). The obtained maximal retention capacities are correlated with the textural properties of applied activated carbon. The roles of acid/base features of activated carbons and of molecular structures of adsorbate molecules have been discussed. The obtained results enabled to estimate the possibility to use the activated carbons in the removal of pharmaceuticals by adsorption. Copyright © 2014 Elsevier B.V. All rights reserved.

In-stream attenuation of neuro-active pharmaceuticals and their metabolites

USGS Publications Warehouse

Writer, Jeffrey; Antweiler, Ronald C.; Ferrar, Imma; Ryan, Joseph N.; Thurman, Michael

2013-01-01

In-stream attenuation was determined for 14 neuro-active pharmaceuticals and associated metabolites. Lagrangian sampling, which follows a parcel of water as it moves downstream, was used to link hydrological and chemical transformation processes. Wastewater loading of neuro-active compounds varied considerably over a span of several hours, and thus a sampling regime was used to verify that the Lagrangian parcel was being sampled and a mechanism was developed to correct measured concentrations if it was not. In-stream attenuation over the 5.4-km evaluated reach could be modeled as pseudo-first-order decay for 11 of the 14 evaluated neuro-active pharmaceutical compounds, illustrating the capacity of streams to reduce conveyance of neuro-active compounds downstream. Fluoxetine and N-desmethyl citalopram were the most rapidly attenuated compounds (t1/2 = 3.6 ± 0.3 h, 4.0 ± 0.2 h, respectively). Lamotrigine, 10,11,-dihydro-10,11,-dihydroxy-carbamazepine, and carbamazepine were the most persistent (t1/2 = 12 ± 2.0 h, 12 ± 2.6 h, 21 ± 4.5 h, respectively). Parent compounds (e.g., buproprion, carbamazepine, lamotrigine) generally were more persistent relative to their metabolites. Several compounds (citalopram, venlafaxine, O-desmethyl-venlafaxine) were not attenuated. It was postulated that the primary mechanism of removal for these compounds was interaction with bed sediments and stream biofilms, based on measured concentrations in stream biofilms and a column experiment using stream sediments.

Pharmaceutical, cosmeceutical, and traditional applications of marine carbohydrates.

PubMed

Ahmed, Abdul Bakrudeen Ali; Adel, Mohaddeseh; Karimi, Pegah; Peidayesh, Mahvash

2014-01-01

Marine carbohydrates are most important organic molecules made by photosynthetic organisms. It is very essential for humankind: the role in being an energy source for the organism and they are considered as an important dissolve organic compound (DOC) in marine environment's sediments. Carbohydrates found in different marine environments in different concentrations. Polysaccharides of carbohydrates play an important role in various fields such as pharmaceutical, food production, cosmeceutical, and so on. Marine organisms are good resources of nutrients, and they are rich carbohydrate in sulfated polysaccharide. Seaweeds (marine microalgae) are used in different pharmaceutical industries, especially in pharmaceutical compound production. Seaweeds have a significant amount of sulfated polysaccharides, which are used in cosmeceutical industry, besides based on the biological applications. Since then, traditional people, cosmetics products, and pharmaceutical applications consider many types of seaweed as an important organism used in food process. Sulfated polysaccharides containing seaweed have potential uses in the blood coagulation system, antiviral activity, antioxidant activity, anticancer activity, immunomodulating activity, antilipidepic activity, etc. Some species of marine organisms are rich in polysaccharides such as sulfated galactans. Various polysaccharides such as agar and alginates, which are extracted from marine organisms, have several applications in food production and cosmeceutical industries. Due to their high health benefits, compound-derived extracts of marine polysaccharides have various applications and traditional people were using them since long time ago. In the future, much attention is supposed to be paid to unraveling the structural, compositional, and sequential properties of marine carbohydrate as well. © 2014 Elsevier Inc. All rights reserved.

Development of diagnostic SPR based biosensor for the detection of pharmaceutical compounds in saliva

NASA Astrophysics Data System (ADS)

Sonny, Susanna; Sesay, Adama M.; Virtanen, Vesa

2010-11-01

The aim of the study is to develop diagnostic tests for the detection of pharmaceutical compounds in saliva. Oral fluid is increasingly being considered as an ideal sample matrix. It can be collected non-invasively and causes less stress to the person being tested. The detection of pharmaceutical compounds and drugs in saliva can give valuable information on individual bases on dose response, usage, characterization and clinical diagnostics. Surface plasmon resonance (SPR) is a highly sensitive, fast and label free analytical technique for the detection of molecular interactions. The specific binding of measured analyte onto the active gold sensing surface of the SPR device induces a refractive index change that can be monitored. To monitor these pharmaceutical compounds in saliva the immunoassays were developed using a SPR instrument. The instrument is equipped with a 670nm laser diode and has two sensing channels. Monoclonal antibodies against the pharmaceutical compounds were used to specifically recognise and capture the compounds which intern will have an effect of the refractive index monitored. Preliminary results show that the immunoassays for cocaine and MDMA (3,4-methylenedioxymethamphetamine) are very sensitive and have linear ranges of 0.01 pg/ml - 1 ng/ml and 0.1 pg/ml - 100 ng/ml, respectively.

Pharmaceutically active compounds in sludge stabilization treatments: anaerobic and aerobic digestion, wastewater stabilization ponds and composting.

PubMed

Martín, Julia; Santos, Juan Luis; Aparicio, Irene; Alonso, Esteban

2015-01-15

Sewage sludge disposal onto lands has been stabilized previously but still many pollutants are not efficiently removed. Special interest has been focused on pharmaceutical compounds due to their potential ecotoxicological effects. Nowadays, there is scarce information about their occurrence in different sludge stabilization treatments. In this work, the occurrence of twenty-two pharmaceutically active compounds has been studied in sludge from four sludge stabilization treatments: anaerobic digestion, aerobic digestion, composting and lagooning. The types of sludge evaluated were primary, secondary, anaerobically-digested and dehydrated, composted, mixed, aerobically-digested and dehydrated and lagoon sludge. Nineteen of the twenty-two pharmaceutically active compounds monitored were detected in sewage sludge. The most contaminated samples were primary sludge, secondary sludge and mixed sludge (the average concentrations of studied compounds in these sludges were 179, 310 and 142 μg/kg dm, respectively) while the mean concentrations found in the other types of sewage sludge were 70 μg/kg dm (aerobically-digested sludge), 63 μg/kg dm (lagoon sludge), 12 μg/kg dm (composted sludge) and 8 μg/kg dm (anaerobically-digested sludge). The antibiotics ciprofloxacin and norfloxacin were found at the highest concentration levels in most of the analyzed sludge samples (up to 2660 and 4328 μg/kg dm, respectively). Anaerobic-digestion treatment reduced more considerably the concentration of most of the studied compounds than aerobic-digestion (especially in the case of bezafibrate and fluoroquinolones) and more than anaerobic stabilization ponds (in the case of acetaminophen, atenolol, bezafibrate, carbamazepine, 17α-ethinylestradiol, naproxen and salicylic acid). Ecotoxicological risk assessment, of sludge application onto soils, has also been evaluated. Risk quotients, expressed as the ratio between the predicted environmental concentration and the predicted non-effect concentration, were lower than 1 for all the pharmaceutically active compounds so no significant risks are expected to occur due to the application of sewage sludge onto soils, except for 17α-ethinylestradiol when chronic toxicity was considered. Copyright © 2014 Elsevier B.V. All rights reserved.

Occurrence and concentrations of pharmaceutical compounds in groundwater used for public drinking-water supply in California.

PubMed

Fram, Miranda S; Belitz, Kenneth

2011-08-15

Pharmaceutical compounds were detected at low concentrations in 2.3% of 1231 samples of groundwater (median depth to top of screened interval in wells=61 m) used for public drinking-water supply in California. Samples were collected statewide for the California State Water Resources Control Board's Groundwater Ambient Monitoring and Assessment (GAMA) Program. Of 14 pharmaceutical compounds analyzed, 7 were detected at concentrations greater than or equal to method detection limits: acetaminophen (used as an analgesic, detection frequency 0.32%, maximum concentration 1.89 μg/L), caffeine (stimulant, 0.24%, 0.29 μg/L), carbamazepine (mood stabilizer, 1.5%, 0.42 μg/L), codeine (opioid analgesic, 0.16%, 0.214 μg/L), p-xanthine (caffeine metabolite, 0.08%, 0.12 μg/L), sulfamethoxazole (antibiotic, 0.41%, 0.17 μg/L), and trimethoprim (antibiotic, 0.08%, 0.018 μg/L). Detection frequencies of pesticides (33%), volatile organic compounds not including trihalomethanes (23%), and trihalomethanes (28%) in the same 1231 samples were significantly higher. Median detected concentration of pharmaceutical compounds was similar to those of volatile organic compounds, and higher than that of pesticides. Pharmaceutical compounds were detected in 3.3% of the 855 samples containing modern groundwater (tritium activity>0.2 TU). Pharmaceutical detections were significantly positively correlated with detections of urban-use herbicides and insecticides, detections of volatile organic compounds, and percentage of urban land use around wells. Groundwater from the Los Angeles metropolitan area had higher detection frequencies of pharmaceuticals and other anthropogenic compounds than groundwater from other areas of the state with similar proportions of urban land use. The higher detection frequencies may reflect that groundwater flow systems in Los Angeles area basins are dominated by engineered recharge and intensive groundwater pumping. Published by Elsevier B.V.

Basics of Compounding with Dilutions and Concentrates.

PubMed

Allen, Loyd V

2017-01-01

Pharmacists use various sources for obtaining the active pharmaceutical ingredient for compounding medications. In many cases, it is the pure drug (United States Pharmacopeia, National Formulary, or similar grade); in some cases, it can be a commercial dosage form; and, in some cases, it may be a dilution or concentrate. If the drug is not present at full strength, then adjustments may be necessary to obtain the required quantity of drug. Also, in many cases, it is necessary to use a dilution or a concentrate of a drug due to safety and quality reasons. Presented within this article are new sources of active pharmaceutical ingredients that are now available to aid pharmacists in meeting future United States Pharmacopeia <800> standards. It is critical that the pharmacist be aware of the strength of the drug and any other excipients that may be available. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Development of a common priority list of pharmaceuticals relevant for the water cycle.

PubMed

de Voogt, P; Janex-Habibi, M-L; Sacher, F; Puijker, L; Mons, M

2009-01-01

Pharmaceutically active compounds (PhACs), including prescription drugs, over-the-counter medications, drugs used in hospitals and veterinary drugs, have been found throughout the water cycle. A desk study was initiated by the Global Water Research Coalition to consolidate a uniform selection of such compounds in order to judge risks of PhACs for the water cycle. By identifying major existing prioritization efforts and evaluating the criteria they use, this study yields a representative and qualitative profile ('umbrella view') of priority pharmaceuticals based on an extensive set of criteria. This can then be used for further studies on analytical methods, occurrence, treatability and potential risks associated with exposure to PhACs in water supply, identifying compounds most likely to be encountered and that may have significant impact on human health. For practical reasons, the present study excludes veterinary drugs. The pragmatic approach adopted provides an efficient tool to manage risks related to pharmaceuticals and provides assistance for selecting compounds for future studies.

The route from problem to solution in multistep continuous flow synthesis of pharmaceutical compounds.

PubMed

Bana, Péter; Örkényi, Róbert; Lövei, Klára; Lakó, Ágnes; Túrós, György István; Éles, János; Faigl, Ferenc; Greiner, István

2017-12-01

Recent advances in the field of continuous flow chemistry allow the multistep preparation of complex molecules such as APIs (Active Pharmaceutical Ingredients) in a telescoped manner. Numerous examples of laboratory-scale applications are described, which are pointing towards novel manufacturing processes of pharmaceutical compounds, in accordance with recent regulatory, economical and quality guidances. The chemical and technical knowledge gained during these studies is considerable; nevertheless, connecting several individual chemical transformations and the attached analytics and purification holds hidden traps. In this review, we summarize innovative solutions for these challenges, in order to benefit chemists aiming to exploit flow chemistry systems for the synthesis of biologically active molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

Occurrence of pharmaceutically active and non-steroidal estrogenic compounds in three different wastewater recycling schemes in Australia.

PubMed

Al-Rifai, Jawad H; Gabelish, Candace L; Schäfer, Andrea I

2007-10-01

The discovery that natural and synthetic chemicals, in the form of excreted hormones and pharmaceuticals, as well as a vast array of compounds with domestic and industrial applications, can enter the environment via wastewater treatment plants and cause a wide variety of environmental and health problems even at very low concentrations, suggests the need for improvement of water recycling. Three Australian wastewater recycling schemes, two of which employ reverse osmosis (RO) technology, the other applying ozonation and biological activated carbon filtration, have been studied for their ability to remove trace organic contaminants including 11 pharmaceutically active compounds and two non-steroidal estrogenic compounds. Contaminant concentrations were determined using a sensitive analytical method comprising solid phase extraction, derivatization and GC with MS using selected ion monitoring. In raw wastewater, concentrations of analgesics and non-steroidal anti-inflammatory medications were comparable to those found in wastewaters around the world. Remarkably, removal efficiencies for the three schemes were superior to literature values and RO was responsible for the greatest proportion of contaminant removal. The ability of RO membranes to concentrate many of the compounds was demonstrated and highlights the need for continued research into monitoring wastewater treatment, concentrate disposal, improved water recycling schemes and ultimately, safer water and a cleaner environment.

21 CFR 212.1 - What are the meanings of the technical terms used in these regulations?

Code of Federal Regulations, 2010 CFR

2010-04-01

... active pharmaceutical ingredient. In-process material means any material fabricated, compounded, blended...-process material, packaging material, or labeling in the production of a PET drug. PET means positron... the Federal Food, Drug, and Cosmetic Act, as amended (21 U.S.C. 321 et seq.). Active pharmaceutical...

Membrane Bioprocesses for Pharmaceutical Micropollutant Removal from Waters

PubMed Central

de Cazes, Matthias; Abejón, Ricardo; Belleville, Marie-Pierre; Sanchez-Marcano, José

2014-01-01

The purpose of this review work is to give an overview of the research reported on bioprocesses for the treatment of domestic or industrial wastewaters (WW) containing pharmaceuticals. Conventional WW treatment technologies are not efficient enough to completely remove all pharmaceuticals from water. Indeed, these compounds are becoming an actual public health problem, because they are more and more present in underground and even in potable waters. Different types of bioprocesses are described in this work: from classical activated sludge systems, which allow the depletion of pharmaceuticals by bio-degradation and adsorption, to enzymatic reactions, which are more focused on the treatment of WW containing a relatively high content of pharmaceuticals and less organic carbon pollution than classical WW. Different aspects concerning the advantages of membrane bioreactors for pharmaceuticals removal are discussed, as well as the more recent studies on enzymatic membrane reactors to the depletion of these recalcitrant compounds. PMID:25295629

The contribution of Raman spectroscopy to the analysis of phase transformations in pharmaceutical compounds.

PubMed

Hédoux, Alain; Guinet, Yannick; Descamps, Marc

2011-09-30

We show in this paper the contribution of the whole Raman spectrum including the phonon spectrum, to detect, identify and characterize polymorphic forms of molecular compounds, and study their stability and transformation. Obtaining these kinds of information is important in the area of pharmaceutical compounds. Two different polymorphic systems are analyzed through investigations in indomethacin and caffeine exposed to variable environmental conditions and various stresses, as possibly throughout the production cycle of the active pharmaceutical ingredient. It is shown the capability of the low-frequency Raman spectroscopy to reveal disorder in the crystalline state, to detect small amorphous or crystalline material, and to elucidate ambiguous polymorphic or polyamorphic situations. Copyright © 2011 Elsevier B.V. All rights reserved.

Removal of pharmaceutically active compounds in nitrifying-denitrifying plants.

PubMed

Suárez, S; Ramil, M; Omil, F; Lema, J M

2005-01-01

The behaviour of nine pharmaceutically active compounds (PhACs) of different diagnostic groups is studied during a nitrifying-denitrifying process in an activated sludge system. The compounds selected cover a wide range of frequently used substances such as anti-epileptics (carbamazepine), tranquillisers (diazepam), anti-depressants (fluoxetine and citalopram), anti-inflammatories (ibuprofen, naproxen and diclofenac) and estrogens (estradiol and ethinylestradiol). The main objective of this research is to investigate the effect of acclimation of biomass on the removal rates of these compounds, either by maintaining a high sludge retention time or at long-term operation. The removal rates achieved for nitrogen and carbon in the experimental unit exceed 90% and were not affected by the addition of PhACs. Carbamazepine, diazepam and diclofenac were only removed to a small extent. On the other hand, higher removal rates have been observed for naproxen and ibuprofen (68% and 82%), respectively.

Occurrence and risk assessment of pharmaceutically active compounds in wastewater treatment plants. A case study: Seville city (Spain).

PubMed

Santos, J L; Aparicio, I; Alonso, E

2007-05-01

The occurrence of four anti-inflammatory drugs (diclofenac, ibuprofen, ketoprofen and naproxen), an antiepileptic drug (carbamazepine) and a nervous stimulant (caffeine) in influent and effluent samples from four wastewater treatment plants (WWTPs) in Seville was evaluated. Removal rates in the WWTPs and risk assessment of the pharmaceutically active compounds have been studied. Analytical determination was carried out by high performance liquid chromatography (HPLC) with diode array (DAD) and fluorescence (Fl) detectors after sample clean up and concentration by solid phase extraction. All pharmaceutically active compounds, except diclofenac, were detected not only in wastewater influents but also in wastewater effluents. Mean concentrations of caffeine, carbamazepine, ketoprofen and naproxen ranged between 0.28-11.44 microg l(-1) and 0.21-2.62 microg l(-1) in influent and effluent wastewater, respectively. Ibuprofen was present in the highest concentrations in the range 12.13-373.11 microg l(-1) and 0.78-48.24 microg l(-1) in influent and effluent wastewater, respectively. Removal rates of the pharmaceuticals ranged between 6 and 98%. Risk quotients, expressed as ratios between the measured environmental concentration (MEC) and the predicted no effect concentrations (PNEC) were higher than 1 for ibuprofen and naproxen in influent wastewater and for ibuprofen in effluent wastewater.

Molecular structure activity on pharmaceutical applications of Phenacetin using spectroscopic investigation

NASA Astrophysics Data System (ADS)

Madanagopal, A.; Periandy, S.; Gayathri, P.; Ramalingam, S.; Xavier, S.

2017-01-01

The pharmaceutical compound; Phenacetin was investigated by analyzing FT-IR, FT-Raman and 1H &13C NMR spectra. The hybrid efficient computational calculations performed for computing physical and chemical parameters. The cause of pharmaceutical activity due to the substitutions; carboxylic, methyl and amine groups in appropriate positions on the pedestal compound was deeply investigated. Moreover, 13C NMR and 1H NMR chemical shifts correlated with TMS standard to explain the truth of compositional ratio of base and ligand groups. The bathochromic shift due to chromophores over the energy levels in UV-Visible region was strongly emphasized the Anti-inflammatory chemical properties. The chemical stability was pronounced by the strong kubo gap which showed the occurring of charge transformation within the molecule. The occurrence of the chemical reaction was feasibly interpreted by Gibbs free energy profile. The standard vibrational analysis stressed the active participation of composed ligand groups for the existence of the analgesic as well as antipyretic properties of the Phenacetin compound. The strong dipole interaction energy utilization for the transition among non-vanishing donor and acceptor for composition of the molecular structure was interpreted.

Independent Community Pharmacists' Perspectives on Compounding in Contemporary Pharmacy Education

PubMed Central

McPherson, Timothy B.; Fontane, Patrick E.; Berry, Tricia; Chereson, Rasma; Bilger, Rhonda

2009-01-01

Objectives To identify compounding practices of independent community pharmacy practitioners in order to make recommendations for the development of curricular objectives for doctor of pharmacy (PharmD) programs. Methods Independent community practitioners were asked about compounding regarding their motivations, common activities, educational exposures, and recommendations for PharmD education. Results Most respondents (69%) accepted compounding as a component of pharmaceutical care and compounded dermatological preparations for local effects, oral solutions, and suspensions at least once a week. Ninety-five percent were exposed to compounding in required pharmacy school courses and most (98%) who identified compounding as a professional service offered in their pharmacy sought additional postgraduate compounding education. Regardless of the extent of compounding emphasis in the practices surveyed, 84% stated that PharmD curricula should include compounding. Conclusions Pharmacy schools should define compounding curricular objectives and develop compounding abilities in a required laboratory course to prepare graduates for pharmaceutical care practice. PMID:19564997

The role of cocrystals in pharmaceutical science.

PubMed

Shan, Ning; Zaworotko, Michael J

2008-05-01

Pharmaceutical cocrystals, a subset of a long known but little-studied class of compounds, represent an emerging class of crystal forms in the context of pharmaceutical science. They are attractive to pharmaceutical scientists because they can significantly diversify the number of crystal forms that exist for a particular active pharmaceutical ingredient (API), and they can lead to improvements in physical properties of clinical relevance. In this article we address pharmaceutical cocrystals from the perspective of design (crystal engineering) and present a series of case studies that demonstrate how they can enhance the solubility, bioavailability, and/or stability of API crystal forms.

Occurrence of human pharmaceuticals in water resources of the United States: A review

USGS Publications Warehouse

Focazio, M.J.; Kolpin, D.W.; Furlong, E.T.

2004-01-01

The widespread environmental presence of some pharmaceuticals and other organic wastewater compounds has been documented globally (e.g. Buser et al. 1998; Ternes 1998; Stumpf et al.1999; Heberer et al. 2001; Kümmerer 2001; Ternes et al. 2001; Scheytt et al. 2001; Golet et al. 2002; Kolpin et al. 2002; Boyd et al. 2003; Metcalf et al. 2003). Recently, there have been several literature reviews and summary studies of the occurrence, fate, transport, and treatment of targeted human pharmaceuticals in wastewater effluent and associated environmental waters across the globe (e.g. Daughton and Ternes 1999; Sedlak et al. 2000; Suter and Giger 2000; Daughton and Jones-Lepp 2001; Jones et al. 2001; Heberer 2002; and Drewes et al. 2002). The occurrence of pharmaceutical compounds in water resources is explained by their ubiquitous use, excretion of large percentages of the mass consumed, and incomplete removal during wastewater treatment (Stumpf et al.1999). The recent increase in detection of trace concentrations (typically less than a part per billion) of pharmaceuticals in water resources across the globe reflects improvements in laboratory analytical methods (Sedlak et al. 2000) and the associated increases in field surveys. The detection of pharmaceutical compounds in large rivers in Europe and in the North Sea (Buser et al. 1998; Ternes 1998; Stumpf et al. 1999) highlighted the fact that highly soluble, trace organic compounds, such as pharmaceuticals, may escape removal in wastewater treatment, and the mixing and concentration of wastewaters through conventional wastewater treatment processes could provide a means of delivering these chemicals to environmental waters in a manner that would contaminate water resources on a large scale at trace levels (Richardson and Bowron 1985). In the United States, some of the first detections of a limited number of pharmaceutically active compounds or their transformation products were found in waters associated with landfill leachates or sewage effluent (Tabak and Bunch 1970; Garrison et al. 1976; Hignite and Azarnoff 1977; Bouwer et al. 1982; Eckel et al. 1991) decades ago. At the time of these studies, other industrial contaminants were the focus of regulatory and scientific interest; therefore, further studies on the environmental occurrence and transport of pharmaceutical compounds were rare.

Imidazopyridines as a source of biological activity and their pharmacological potentials-Infrared and Raman spectroscopic evidence of their content in pharmaceuticals and plant materials.

PubMed

Dymińska, Lucyna

2015-09-15

Derivatives of imidazopyridine are used in medicinal chemistry due to their biological and pharmaceutical properties. This review article presents imidazopyridine pharmacological activity as antiinflammatory, anticancer, antiviral, antiosteoporotic, antiparasitic, and antihypertensive agents by studying its various synthesized derivatives. Some of compounds with imidazopyridine skeleton are used in psychiatry and autoimmune disorders. The presented data suggest that IR and Raman spectra measurements are a good methods for identification and characterization of the compounds containing imidazopyridine core. Two stretching vibrations: νas(Φ) and νs(Φ) are of a diagnostic importance. The appearance of these bands in the IR and Raman spectra of some plants, tissues and pharmaceuticals confirms the presence of imidazopyridine skeleton in these substances. Copyright © 2015 Elsevier Ltd. All rights reserved.

Small molecule compound logistics outsourcing--going beyond the "thought experiment".

PubMed

Ramsay, Devon L; Kwasnoski, Joseph D; Caldwell, Gary W

2012-01-01

Increasing pressure on the pharmaceutical industry to reduce cost and focus internal resources on "high value" activities is driving a trend to outsource traditionally "in-house" drug discovery activities. Compound collections are typically viewed as drug discovery's "crown jewels"; however, in late 2007, Johnson & Johnson Pharmaceutical Research & Development (J PRD) took a bold step to move their entire North American compound inventory and processing capability to an external third party vendor. The authors discuss the combination model implemented, that of local compound logistics site support with an outsourced centralized processing center. Some of the lessons learned over the past five years were predictable while others were unexpected. The substantial cost savings, improved local service response and flexible platform to adjust to changing business needs resulted. Continued sustainable success relies heavily upon maintaining internal headcount dedicated to vendor management, an open collaboration approach and a solid information technology infrastructure with complete transparency and visibility.

Skin delivery of antioxidant surfactants based on gallic acid and hydroxytyrosol.

PubMed

Alonso, Cristina; Lucas, Ricardo; Barba, Clara; Marti, Meritxell; Rubio, Laia; Comelles, Francesc; Morales, Juan Carlos; Coderch, Luisa; Parra, José Luís

2015-07-01

The aim of this study has been to investigate the dermal absorption profile of the antioxidant compounds gallic acid and hydroxytyrosol as well as their derivatives, hexanoate (hexyl gallate and hydroxytyrosol hexanoate) and octanoate (octyl gallate and octanoate derivative) alkyl esters (antioxidant surfactants). Previously, the scavenging capacity of these compounds, expressed as efficient dose ED50, has also determined. The percutaneous absorption of these compounds was obtained by an in vitro methodology using porcine skin biopsies on Franz static diffusion cells. The antiradical activity of compounds was determined using the 1,1-diphenyl-2-picrylhydrazyl free radical method. The percutaneous penetration results show the presence of antioxidants in all layers of the skin. The content of the cutaneously absorbed compound is higher for the antioxidant surfactants (ester derivatives). This particular behaviour could be due to the higher hydrophobicity of these compounds and the presence of surface activity in the antioxidant surfactants. These new antioxidant surfactants display optimum properties, which may be useful in the preparation of emulsified systems in cosmetic and pharmaceutical formulations because of their suitable surface activity and because they can protect the skin from oxidative damage. © 2015 Royal Pharmaceutical Society.

Fate and removal of pharmaceuticals and illicit drugs in conventional and membrane bioreactor wastewater treatment plants and by riverbank filtration.

PubMed

Petrovic, Mira; de Alda, Maria Jose Lopez; Diaz-Cruz, Silvia; Postigo, Cristina; Radjenovic, Jelena; Gros, Meritxell; Barcelo, Damià

2009-10-13

Pharmaceutically active compounds (PhACs) and drugs of abuse (DAs) are two important groups of emerging environmental contaminants that have raised an increasing interest in the scientific community. A number of studies revealed their presence in the environment. This is mainly due to the fact that some compounds are not efficiently removed during wastewater treatment processes, being able to reach surface and groundwater and subsequently, drinking waters. This paper reviews the data regarding the levels of pharmaceuticals and illicit drugs detected in wastewaters and gives an overview of their removal by conventional treatment technologies (applying activated sludge) as well as advanced treatments such as membrane bioreactor. The paper also gives an overview of bank filtration practices at managed aquifer recharge sites and discusses the potential of this approach to mitigate the contamination by PhACs and DAs.

Predicting the activity and toxicity of new psychoactive substances: a pharmaceutical industry perspective.

PubMed

Leach, Andrew G

2014-01-01

Predicting the effect that new compounds might have when administered to human beings is a common desire shared by researchers in the pharmaceutical industry and those interested in psychoactive compounds (illicit or otherwise). The experience of the pharmaceutical industry is that making such predictions at a usefully accurate level is not only difficult but that even when billions of dollars are spent to ensure that only compounds likely to have a desired effect without unacceptable side-effects are dosed to humans in clinical trials, they fail in more than 90% of cases. A range of experimental and computational techniques is used and they are placed in their context in this paper. The particular roles played by computational techniques and their limitations are highlighted; these techniques are used primarily to reduce the number of experiments that must be performed but cannot replace those experiments. Copyright © 2013 John Wiley & Sons, Ltd.

Stability of Allopurinol, Amitriptyline Hydrochloride, Carbamazepine, Domperidone, Isoniazid, Ketoconazole, Lisinopril, Naproxen, Paracetamol (Acetaminophen), and Sertraline Hydrochloride in SyrSpend SF PH4 Oral Suspensions.

PubMed

Polonini, Hudson C; Loures, Sharlene; de Araujo, Edson Peter; Brandão, Marcos Antônio F; Ferreira, Anderson O

2016-01-01

Oral liquids are safe alternatives to solid dosage forms, notably for elderly and pediatric patients that present dysphagia. The use of ready-to-use suspending vehicles such as SyrSpend SF PH4 is a suitable resource for pharmacists as they constitute a safe and timesaving option that has been studied often. The objective of this study was to evaluate the stability of 10 commonly used active pharmaceutical ingredients (allopurinol 20 mg/mL; amitriptyline hydrochloride 10 mg/mL; carbamazepine 25 mg/mL; domperidone 5 mg/mL; isoniazid 10 mg/mL; ketoconazole 20 mg/mL; lisinopril 1 mg/mL; naproxen 25 mg/mL; paracetamol [acetaminophen] 50 mg/mL; and sertraline hydrochloride 10 mg/mL) compounded in oral suspensions using SyrSpend SF PH4 as the vehicle throughout the study period and stored both at controlled refrigerated (2°C to 8°C) and room temperature (20°C to 25°C). Stability was assessed by means of measuring the percent recovery at varying time points throughout a 90-day period. The quantification of the active pharmaceutical ingredients was performed by high-performance liquid chromatography through a stability-indicating method. Methods were adequately validated. Forced-degradation studies showed that at least one parameter influenced the stability of the active pharmaceutical ingredients. All suspensions were assayed and showed active pharmaceutical ingredient contents between 90% and 110% during the 90-day study period. Although the forced-degradation experiments led to visible fluctuations in the chromatographic responses, the final preparations were stable in the storage conditions. The beyond-use dates of the preparations were found to be at least 90 days for all suspensions, both for controlled refrigerated temperature and room temperature. This confirms that SyrSpend SF PH4 is a stable suspending vehicle for compounding with a broad range of different active pharmaceutical ingredients for different medical usages. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Haberlea rhodopensis: pharmaceutical and medical potential as a food additive.

PubMed

Todorova, Roumiana; Atanasov, Atanas T

2016-01-01

This review discusses the potential of Haberlea rhodopensis as a food additive. The following are described: plant distribution, reproduction, cultivation, propagation and resurrection properties; extraction, isolation and screening of biologically active compounds; metabolite changes during dehydration; phytotherapy-related properties such as antioxidant potential and free radical-scavenging activities, antioxidant skin effect, antibacterial activity, cytotoxic activity and cancer-modulating effect, radioprotective effect, chemoprotective effect, immunologic effect; present use in homoeopathy and cosmetics, pharmacological and economical importance; perspectives based on the ethnobotanical data for medicinal, cosmetic or ritual attributes. H. rhodopensis showed unique medical and pharmaceutical potential, related to antioxidant, antimicrobial, antimutagenic, anticancer, radioprotective, chemoprotective and immunological properties. H. rhodopensis extracts lack any cytotoxic activity and could be used in phytotherapy. The metabolic profiling of H. rhodopensis extracts revealed the presence of biologically active compounds, possessing antiradical and other physiological activities, useful for design of in vitro synthesised analogues and drugs.

IDENTIFYING COMPOUNDS DESPITE CHROMATOGRAPHY LIMITATIONS: ORGANOPHOSPHATES IN TREATED SEWAGE

EPA Science Inventory

Highly concentrated extracts of sewage treatment plant (STP) effluents contain detectable
levels of dozens of compounds resulting from human activities. Recent concern over use and
disposal of Pharmaceuticals and Personal Care Products (PPCPS) (1) has stimulated interest ...

40 CFR 439.41 - Special definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... STANDARDS (CONTINUED) PHARMACEUTICAL MANUFACTURING POINT SOURCE CATEGORY Mixing/Compounding and Formulation § 439.41 Special definitions. For the purpose of this subpart: (a) Mixing, compounding, and formulating... pharmaceutical product manufactured by blending, mixing, compounding, and formulating pharmaceutical ingredients...

Removal of naproxen and bezafibrate by activated sludge under aerobic conditions: kinetics and effect of substrates.

PubMed

Tang, Ying; Li, Xiao-Ming; Xu, Zhen-Cheng; Guo, Qing-Wei; Hong, Cheng-Yang; Bing, Yong-Xin

2014-01-01

Naproxen and bezafibrate fall into the category of pharmaceuticals that have been widely detected in the aquatic environment, and one of the major sources is the effluent discharge from wastewater treatment plants. This study investigated the sorption and degradation kinetics of naproxen and bezafibrate in the presence of activated sludge under aerobic conditions. Experimental results indicated that the adsorption of pharmaceuticals by activated sludge was rapid, and the relative adsorbabilities of the two-target compounds were based on their log Kow and pKa values. The adsorption data could be well interpreted by the pseudo-second-order kinetic model. The degradation process could be described by the pseudo-first-order kinetic model, whereas the pseudo-second-order kinetics were also well suited to describe the degradation process of the selected compounds at low concentrations. Bezafibrate was more easily degraded by activated sludge compared with naproxen. The spiked concentration of the two-target compounds was negatively correlated with k1 and k2s , indicating that the substrate inhibition effect occurred at the range of studied concentrations. Chemical oxygen demand (COD) did not associate with naproxen degradation; thus, COD is not an alternative method that could be applied to investigate natural organic matter's impact on degradation of pharmaceuticals by activated sludge. © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Improved removal of estrogenic and pharmaceutical compounds in sewage effluent by full scale granular activated carbon: impact on receiving river water.

PubMed

Grover, D P; Zhou, J L; Frickers, P E; Readman, J W

2011-01-30

Sewage effluents are widely recognised as the main source of emerging contaminants, such as endocrine disrupting chemicals (EDCs) and pharmaceuticals in surface waters. A full-scale granular activated carbon (GAC) plant has been installed as an advanced technology for the removal of these contaminants, in a major sewage treatment works (STW) in South-West England as part of the UK National Demonstration Programme for EDCs. This study presented for the first time, an assessment of the impact of a recently commissioned, post-tertiary GAC plant in the removal of emerging contaminants in a working STW. Through regular sampling followed by solid-phase extraction and analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS), a significant reduction in the concentrations of steroidal estrogens was observed (>43-64%). In addition, significant reductions were observed for many of the pharmaceutical compounds such as mebeverine (84-99%), although the reduction was less dramatic for some of the more widely used pharmaceuticals analysed, including carbamazepine and propranolol (17-23%). Copyright © 2010 Elsevier B.V. All rights reserved.

Examining pharmaceuticals using terahertz spectroscopy

NASA Astrophysics Data System (ADS)

Sulovská, Kateřina; Křesálek, Vojtěch

2015-10-01

Pharmaceutical trafficking is common issue in countries where they are under stricter dispensing regime with monitoring of users. Most commonly smuggled pharmaceuticals include trade names Paralen Plus, Modafen, Clarinase repetabs, Aspirin complex, etc. These are transported mainly from Eastern Europe (e.g. Poland, Ukraine, Russia) to countries like Czech Republic, which is said to have one of the highest number of methamphetamine producers in Europe. The aim of this paper is to describe the possibility of terahertz spectroscopy utilization as an examining tool to distinguish between pharmaceuticals containing pseudoephedrine compounds and those without it. Selected medicaments for experimental part contain as an active ingredient pseudoephedrine hydrochloride or pseudoephedrine sulphate. Results show a possibility to find a pseudoephedrine compound spectra in samples according to previously computed and experimentally found ones, and point out that spectra of same brand names pills may vary according to their expiration date, batch, and amount of absorbed water vapours from ambience. Mislead spectrum also occurs during experimental work in a sample without chosen active ingredient, which shows persistent minor inconveniences of terahertz spectroscopy. All measurement were done on the TPS Spectra 3000 instrument.

Adventures in the Environmental World and Environmental Microbiology Sampling of Air for Pharmaceutical Sterile Compounding.

PubMed

Ligugnana, Roberto

2017-01-01

Chapter <797> issued by the United States Pharmacopeial Convention, Inc. is the standard for sterile compounding. It is designed to reduce the number of patient infections due to contaminated pharmaceutical preparation. This regulation applies to all staff who prepare compounded sterile preparations and all places where they are produced, including hospitals, clinics, pharmacies, and physician's offices. This article provides the history of environmental microbiology and provides a discussion on environmental microbiology sampling of air for pharmaceutical sterile compounding. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Science Plan U.S. Geological Survey Florida District

DTIC Science & Technology

2001-01-01

coastline of the United States during a particularly active period of hurricane activity in 1998. endocrine disruptors , are beginning to receive...reconnaissance sampling for emergent contaminants (pharmaceuticals, pesticides, endocrine disruptor compounds) to develop additional projects. Figure 31...pathogens, and endocrine disruptor compounds. (Issue 4) • Evaluation of new instrumentation for specific applications in Florida, such as

Drugs and Drug-Like Compounds: Discriminating Approved Pharmaceuticals from Screening-Library Compounds

NASA Astrophysics Data System (ADS)

Schierz, Amanda C.; King, Ross D.

Compounds in drug screening-libraries should resemble pharmaceuticals. To operationally test this, we analysed the compounds in terms of known drug-like filters and developed a novel machine learning method to discriminate approved pharmaceuticals from “drug-like” compounds. This method uses both structural features and molecular properties for discrimination. The method has an estimated accuracy of 91% in discriminating between the Maybridge HitFinder library and approved pharmaceuticals, and 99% between the NATDiverse collection (from Analyticon Discovery) and approved pharmaceuticals. These results show that Lipinski’s Rule of 5 for oral absorption is not sufficient to describe “drug-likeness” and be the main basis of screening-library design.

Pharmaceutical Compounds Studied Using NEXAFS

NASA Astrophysics Data System (ADS)

Murray Booth, A.; Braun, Simon; Lonsbourough, Tom; Purton, John; Patel, Sunil; Schroeder, Sven L. M.

2007-02-01

Total Electron Yield (TEY) oxygen K-edge NEXAFS detects the presence of strongly adsorbed water molecules on poloxamer-coated pharmaceutical actives, which provides a useful spectroscopic indicator for bioavailability. The results are supported by complementary XPS measurements. Carbon K-edge spectra obtained in a high-pressure NEXAFS cell were used in situ to establish how a polymer coating spread on a drug surface by using humidity induced dispersion of the coating. Finally, we demonstrate how combined Carbon and Oxygen K-edge measurements can be used to characterize amorphous surface layers on micronised crystals of a drug compound.

Virucidal activities of medium- and long-chain fatty alcohols and lipids against respiratory syncytial virus and parainfluenza virus type 2: comparison at different pH levels.

PubMed

Hilmarsson, H; Traustason, B S; Kristmundsdóttir, T; Thormar, H

2007-01-01

Recent studies have shown that some lipids and fatty alcohols have microbicidal activities against a broad variety of pathogens. In this study, virucidal activities of fatty acids, monoglycerides and fatty alcohols were tested against respiratory syncytial virus (RSV) and human parainfluenza virus type 2 (HPIV2) at different concentrations, times and pH levels. The most active compounds were mixed with milk products and fruit juices and the mixtures tested for virucidal effects. The aim was to determine which compounds are the most active against these respiratory viruses and could possibly be used in pharmaceutical formulations or as additives to milk products or juice. Several compounds caused a significant inactivation of virus, and there was generally a good agreement between the activities against RSV and parainfluenza virus. By changing the pH from 7 to 4.2, the virucidal activities of some of the compounds were greatly increased, i.e., they inactivated virus in a shorter time and at lower concentrations. The most active compound tested was 1-monoglyceride of capric acid, monocaprin, which also showed activity against influenza A virus and significant virucidal activities after addition to milk products and fruit juices, even at a concentration as low as 0.06-0.12%. The significant virucidal activities of fatty alcohols and lipids on RSV and parainfluenza virus demonstrated in this in vitro study raise the question of the feasibility of using such compounds as ingredients in pharmaceutical dosage forms against respiratory infections caused by these viruses, and possibly other paramyxo- and myxoviruses.

Pharmaceutical Raw Material Identification Using Miniature Near-Infrared (MicroNIR) Spectroscopy and Supervised Pattern Recognition Using Support Vector Machine

PubMed Central

Hsiung, Chang; Pederson, Christopher G.; Zou, Peng; Smith, Valton; von Gunten, Marc; O’Brien, Nada A.

2016-01-01

Near-infrared spectroscopy as a rapid and non-destructive analytical technique offers great advantages for pharmaceutical raw material identification (RMID) to fulfill the quality and safety requirements in pharmaceutical industry. In this study, we demonstrated the use of portable miniature near-infrared (MicroNIR) spectrometers for NIR-based pharmaceutical RMID and solved two challenges in this area, model transferability and large-scale classification, with the aid of support vector machine (SVM) modeling. We used a set of 19 pharmaceutical compounds including various active pharmaceutical ingredients (APIs) and excipients and six MicroNIR spectrometers to test model transferability. For the test of large-scale classification, we used another set of 253 pharmaceutical compounds comprised of both chemically and physically different APIs and excipients. We compared SVM with conventional chemometric modeling techniques, including soft independent modeling of class analogy, partial least squares discriminant analysis, linear discriminant analysis, and quadratic discriminant analysis. Support vector machine modeling using a linear kernel, especially when combined with a hierarchical scheme, exhibited excellent performance in both model transferability and large-scale classification. Hence, ultra-compact, portable and robust MicroNIR spectrometers coupled with SVM modeling can make on-site and in situ pharmaceutical RMID for large-volume applications highly achievable. PMID:27029624

Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 2. Model prediction.

PubMed

Yu, Zirui; Peldszus, Sigrid; Huck, Peter M

2009-03-01

The adsorption of two representative pharmaceutically active compounds (PhACs)-naproxen and carbamazepine and one endocrine disrupting compound (EDC)-nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surface diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol.

Identifying relationships between unrelated pharmaceutical target proteins on the basis of shared active compounds.

PubMed

Miljković, Filip; Kunimoto, Ryo; Bajorath, Jürgen

2017-08-01

Computational exploration of small-molecule-based relationships between target proteins from different families. Target annotations of drugs and other bioactive compounds were systematically analyzed on the basis of high-confidence activity data. A total of 286 novel chemical links were established between distantly related or unrelated target proteins. These relationships involved a total of 1859 bioactive compounds including 147 drugs and 141 targets. Computational analysis of large amounts of compounds and activity data has revealed unexpected relationships between diverse target proteins on the basis of compounds they share. These relationships are relevant for drug discovery efforts. Target pairs that we have identified and associated compound information are made freely available.

Fate of pharmaceutical and trace organic compounds in three septic system plumes, Ontario, Canada.

PubMed

Carrara, Cherilyn; Ptacek, Carol J; Robertson, William D; Blowes, David W; Moncur, Michael C; Sverko, Ed; Backus, Sean

2008-04-15

Three high volume septic systems in Ontario, Canada, were examined to assess the potential for onsite wastewatertreatment systems to release pharmaceutical compounds to the environment and to evaluate the mobility of these compounds in receiving aquifers. Wastewater samples were collected from the septic tanks, and groundwater samples were collected below and down gradient of the infiltration beds and analyzed for a suite of commonly used pharmaceutical and trace organic compounds. The septic tank samples contained elevated concentrations of several pharmaceutical compounds. Ten of the 12 compounds analyzed were detected in groundwater at one or more sites at concentrations in the low ng L(-1) to low microg L(-1) range. Large differences among the sites were observed in both the number of detections and the concentrations of the pharmaceutical compounds. Of the compounds analyzed, ibuprofen, gemfibrozil, and naproxen were observed to be transported atthe highest concentrations and greatest distances from the infiltration source areas, particularly in anoxic zones of the plumes.

HPLC Determination of Caffeine and Paraxanthine in Urine: An Assay for Cytochrome P450 1A2 Activity

ERIC Educational Resources Information Center

Furge, Laura Lowe; Fletke, Kyle J.

2007-01-01

Cytochrome P450 enzymes are a family of heme-containing proteins located throughout the body with roles in metabolism of endogenous and exogenous compounds. Among exogenous compounds, clinically relevant pharmaceutical agents are nearly all metabolized by P450 enzymes. However, the activity of the different cytochrome P450 enzymes varies among…

Monitoring the occurrence of emerging contaminants in treated wastewater and groundwater between 2008 and 2010. The Baix Llobregat (Barcelona, Spain).

PubMed

Cabeza, Y; Candela, L; Ronen, D; Teijon, G

2012-11-15

The occurrence of 166 emerging compounds and four heavy metals (Cd, Ni, Hg and Pb) in treated wastewater and groundwater has been monitored at the Llobregat delta (Barcelona, Spain) over a period of 3 years. Selected compounds were pharmaceuticals, personal care products (PCPs), dioxins, polycyclic aromatic hydrocarbons (PAHs) and priority substances included in the 2008/105/CE Directive. Analysis was performed in tertiary treated wastewater (TWW), after an additional treatment of ultrafiltration reverse osmosis and UV disinfection, and groundwater from a deep confined aquifer. This aquifer is artificially recharged with TWW through injection wells. After the advanced treatment, 38 pharmaceuticals, 9 PCPs, 9 pesticides and 7 PAHs still showed a frequency of detection higher than 25% in the TWW, although at low concentration levels (ng/l). Not all active compounds found in the TWW were present in groundwater, indicating possible degradation within the aquifer media after the injection. A number of chemicals, mainly 10 pesticides and 10 pharmaceuticals were only present in groundwater samples, confirming a different origin than the injected TWW, probably agricultural activities and/or infiltration of poorly treated wastewater. Copyright © 2012 Elsevier B.V. All rights reserved.

Basics of Compounding: Clinical Pharmaceutics, Part 2.

PubMed

Allen, Loyd V

2016-01-01

This article represents part 2 of a 2-part article on the topic of clinical pharmaceutics. Pharmaceutics is relevant far beyond the pharmaceutical industry, compounding, and the laboratory. Pharmaceutics can be used to solve many clinical problems in medication therapy. A pharmacists' knowledge of the physicochemical aspects of drugs and drug products should help the patient, physician, and healthcare professionals resolve issues in the increasingly complex world of modern medicine. Part 1 of this series of articles discussed incompatibilities which can directly affect a clinical outcome and utilized pharmaceutics case examples of the application and importance of clinical pharmaceutics covering different characteristics. Part 2 continues to illustrate the scientific principles and clinical effects involved in clinical pharmaceutics. Also covered in this article are many of the scientific principles in typical to patient care. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Orodispersible Films for Compounding Pharmacies.

PubMed

Ferreira, Anderson O; Brandão, Marcos Antônio F; Raposo, Francisco José; Polonini, Hudson C; Raposo, Nádia Rezende Barbosa

2017-01-01

Orodispersible film can be defined as a solid pharmaceutical form intended for the delivery and rapid local or systemic release of active ingredients, consisting of a water-soluble polymer film that hydrates rapidly, adhering and dissolving immediately when placed on the tongue or in the oral cavity (oral, palatal, gingival, lingual, or sublingual), without the need for water administration or mastication. Due to its outstanding importance in cases of emergency, practicality of use by patients in transit, and high adherence, orodispersible film has evolved in popularity and success among consumers. It is a promising dosage form for compounding pharmacies, as simpler technologies are being developed to make the compound process easier and faster for the pharmacist. This article aims to explore some of the basics on orodispersible film and the main possible preparations to be developed in compounding pharmacies worldwide. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Adsorption of Selected Pharmaceutical Compounds onto Activated Carbon in Dilute Aqueous Solutions Exemplified by Acetaminophen, Diclofenac, and Sulfamethoxazole.

PubMed

Chang, E-E; Wan, Jan-Chi; Kim, Hyunook; Liang, Chung-Huei; Dai, Yung-Dun; Chiang, Pen-Chi

2015-01-01

The adsorption of three pharmaceuticals, namely, acetaminophen, diclofenac, and sulfamethoxazole onto granular activated carbon (GAC), was investigated. To study competitive adsorption, both dynamic and steady-state adsorption experiments were conducted by careful selection of pharmaceuticals with various affinities and molecular size. The effective diffusion coefficient of the adsorbate was increased with decease in particle size of GAC. The adsorption affinity represented as Langmuir was consistent with the ranking of the octanol-water partition coefficient, K(ow). The adsorption behavior in binary or tertiary systems could be described by competition adsorption. In the binary system adsorption replacement occurred, under which the adsorbate with the smaller K(ow) was replaced by the one with larger K(ow). Results also indicated that portion of the micropores could be occupied only by the small target compound, but not the larger adsorbates. In multiple-component systems the competition adsorption might significantly be affected by the macropores and less by the meso- or micropores.

Adsorption of Selected Pharmaceutical Compounds onto Activated Carbon in Dilute Aqueous Solutions Exemplified by Acetaminophen, Diclofenac, and Sulfamethoxazole

PubMed Central

Chang, E.-E.; Wan, Jan-Chi; Liang, Chung-Huei; Dai, Yung-Dun; Chiang, Pen-Chi

2015-01-01

The adsorption of three pharmaceuticals, namely, acetaminophen, diclofenac, and sulfamethoxazole onto granular activated carbon (GAC), was investigated. To study competitive adsorption, both dynamic and steady-state adsorption experiments were conducted by careful selection of pharmaceuticals with various affinities and molecular size. The effective diffusion coefficient of the adsorbate was increased with decease in particle size of GAC. The adsorption affinity represented as Langmuir was consistent with the ranking of the octanol-water partition coefficient, K ow. The adsorption behavior in binary or tertiary systems could be described by competition adsorption. In the binary system adsorption replacement occurred, under which the adsorbate with the smaller K ow was replaced by the one with larger K ow. Results also indicated that portion of the micropores could be occupied only by the small target compound, but not the larger adsorbates. In multiple-component systems the competition adsorption might significantly be affected by the macropores and less by the meso- or micropores. PMID:26078989

Biobusiness in the pharmaceutical industry.

PubMed

Werner, R G

1987-09-01

Although conventional biotechnology used for the synthesis of antibiotics, vitamins, amino acids, nucleotides, enzyme inhibitors and immunomodulating compounds has still a major impact in the production of pharmaceutical compounds, the importance of the new biotechnology is increasing. Whereas in conventional biotechnology naturally occurring strains are screened for production of pharmacologically active compounds, in new biotechnology known organisms are programmed by genetic engineering to produce a distinct protein or glycoprotein of human origin for substitution therapy. Such complex compounds from new biotechnology can be divided into products which might replace compounds which are already on the market by safer recombinant products such as human insulin, human growth hormone, urokinase, factor VIII and products which are new on the market such as interferons, lymphokines, tissue plasminogen activator, oligonucleotide probes, monoclonal antibodies and subunit vaccines. However, only a few of these recombinant products have reached the market such as human insulin, interferon alpha, interferon beta, human growth hormone and recombivax HB. In most cases, depending on the difficulties in demonstrating clinical efficacy, the investigated drugs have reached the marketing phase much faster than conventional chemical drugs. Return on investment of biotechnical produced pharmaceutics mainly depends on the issues of whether the product has to compete with chemically synthesized drugs, whether it is totally new but competes with other bioproducts, whether it is exceptional but the proof of clinical efficacy is difficult, or whether it is totally new and clinical studies are promising.(ABSTRACT TRUNCATED AT 250 WORDS)

Basics of Compounding: Clinical Pharmaceutics, Part 1.

PubMed

Allen, Loyd V

2016-01-01

Pharmaceutics is relevant far beyond the pharmaceutical industry, compounding, and the laboratory. Pharmaceutics can be used to solve many clinical problems in medication therapy. A pharmacists' knowledge of the physicochemical aspects of drugs and drug products should help the patient, physician, and healthcare professionals resolve issues in the increasingly complex world of modern medicine. Pharmacy is unique as it contains a knowledge base significantly different from that of physicians, nurses, and other health-related practitioners. The separation of the science and the practice of pharmacy have prevented the complete utilization of pharmaceutical sciences in the clinical environment far too long. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

The influence of natural organic matter and cations on the rejection of endocrine disrupting and pharmaceutically active compounds by nanofiltration.

PubMed

Comerton, Anna M; Andrews, Robert C; Bagley, David M

2009-02-01

The impact of natural organic matter (NOM) and cations on the rejection of five endocrine disrupting compounds (EDCs) and pharmaceutically active compounds (PhACs) (acetaminophen, carbamazepine, estrone, gemfibrozil, oxybenzone) by nanofiltration (NF) was examined. The water matrices included membrane bioreactor (MBR) effluent, Lake Ontario water and laboratory-prepared waters modelled to represent the characteristics of the Lake Ontario water. The impact of cations in natural waters on compound rejection was also examined by doubling the natural cation concentration (calcium, magnesium, sodium) in both the Lake Ontario water and the MBR effluent. The presence of Suwannee River NOM spiked into laboratory-grade water was found to cause an increase in compound NF rejection. In addition, the presence of cations alone in laboratory-grade water did not have a significant impact on rejection with the exception of the polar compound gemfibrozil. However, when cation concentration in natural waters was increased, a significant decrease in the rejection of EDCs and PhACs was observed. This suggests that the presence of cations may result in a reduction in the association of EDCs and PhACs with NOM.

Prioritizing human pharmaceuticals for ecological risks in the freshwater environment of Korea.

PubMed

Ji, Kyunghee; Han, Eun Jeong; Back, Sunhyoung; Park, Jeongim; Ryu, Jisung; Choi, Kyungho

2016-04-01

Pharmaceutical residues are potential threats to aquatic ecosystems. Because more than 3000 active pharmaceutical ingredients (APIs) are in use, identifying high-priority pharmaceuticals is important for developing appropriate management options. Priority pharmaceuticals may vary by geographical region, because their occurrence levels can be influenced by demographic, societal, and regional characteristics. In the present study, the authors prioritized human pharmaceuticals of potential ecological risk in the Korean water environment, based on amount of use, biological activity, and regional hydrologic characteristics. For this purpose, the authors estimated the amounts of annual production of 695 human APIs in Korea. Then derived predicted environmental concentrations, using 2 approaches, to develop an initial candidate list of target pharmaceuticals. Major antineoplastic drugs and hormones were added in the initial candidate list regardless of their production amount because of their high biological activity potential. The predicted no effect concentrations were derived for those pharmaceuticals based on ecotoxicity information available in the literature or by model prediction. Priority lists of human pharmaceuticals were developed based on ecological risks and availability of relevant information. Those priority APIs identified include acetaminophen, clarithromycin, ciprofloxacin, ofloxacin, metformin, and norethisterone. Many of these pharmaceuticals have been neither adequately monitored nor assessed for risks in Korea. Further efforts are needed to improve these lists and to develop management decisions for these compounds in Korean water. © 2015 SETAC.

Occurrence of pharmaceuticals in river water and their elimination in a pilot-scale drinking water treatment plant.

PubMed

Vieno, Niina M; Härkki, Heli; Tuhkanen, Tuula; Kronberg, Leif

2007-07-15

The occurrence of four beta blockers, one antiepileptic drug, one lipid regulator, four anti-inflammatories, and three fluoroquinolones was studied in a river receiving sewage effluents. All compounds but two of the fluoroquinolones were observed in the water above their limit of quantification concentrations. The highest concentrations (up to 107 ng L(-1)) of the compounds were measured during the winter months. The river water was passed to a pilot-scale drinking water treatment plant, and the elimination of the pharmaceuticals was followed during the treatment. The processes applied by the plant consisted of ferric salt coagulation, rapid sand filtration, ozonation, two-stage granular activated carbon filtration (GAC), and UV disinfection. Following the coagulation, sedimentation, and rapid sand filtration, the studied pharmaceuticals were found to be eliminated only by an average of 13%. An efficient elimination was found to take place during ozonation at an ozone dose of about 1 mg L(-1) (i.e., 0.2-0.4 mg of O3/ mg of TOC). Following this treatment, the concentrations of the pharmaceuticals dropped to below the quantification limits with the exception of ciprofloxacin. Atenolol, sotalol, and ciprofloxacin, the most hydrophilic of the studied pharmaceuticals, were not fully eliminated during the GAC filtrations. All in all, the treatment train was found to very effectively eliminate the pharmaceuticals from the rawwater. The only compound that was found to pass almost unaffected through all the treatment steps was ciprofloxacin.

Peculiar surface behavior of some ionic liquids based on active pharmaceutical ingredients

NASA Astrophysics Data System (ADS)

Restolho, José; Mata, José Luis; Saramago, Benilde

2011-02-01

The ionic liquids based on biologically active cations and anions, commonly designated by ionic liquids based on active pharmaceutical ingredients (ILs-APIs), are interesting compounds for use in pharmaceutical applications. Lidocaine docusate, ranitidine docusate, and didecyldimethylammonium ibuprofen are examples of promising ILs-APIs that were recently synthesized. They were submitted to biological testing and calorimetric measurements, but nothing is known about their surface properties. In this work, we measured the surface tension and the contact angles on both hydrophilic and hydrophobic surfaces in a temperature range as wide as possible. Based on the wettability data, the polarity fractions were estimated using the Fowkes theory. The peculiar surface behavior observed was tentatively attributed to the presence of mesophases.

Pharmacological Potential of Sea Cucumbers

PubMed Central

Khotimchenko, Yuri

2018-01-01

This review presents a detailed analysis of published research data focused on the pharmacological activity exerted by biologically active compounds isolated from sea cucumbers belonging to the class of Holothuroidea, phylum Echinodermata. The review contains descriptions of the structure, physico-chemical properties and pharmacological effects of these active substances. Particular attention is given to compounds with anticoagulant, antithrombotic, antioxidant, anticancer, anti-infectious, immune-stimulating and anti-ACE (angiotensin converting enzyme) activities as well as to the substances exerting a regulating influence on lipid and carbohydrate metabolism. All these compounds may be considered as prototypes for development of new pharmaceutical substances and medicines. PMID:29724051

Biotechnology, nanotechnology, and pharmacogenomics and pharmaceutical compounding, Part 1.

PubMed

Allen, Loyd V

2015-01-01

The world of pharmaceuticals is changing rapidly as biotechnology continues to grow and nanotechnology appears on the horizon. Biotechnology is gaining in importance in extemporaneous pharmaceutical compounding, and nanotechnology and pharmacogenomics could drastically change the practice of pharmacy. This article discusses biotechnology and the factors to consider when compounding biotechnology drugs.

Analytic Methods Used in Quality Control in a Compounding Pharmacy.

PubMed

Allen, Loyd V

2017-01-01

Analytical testing will no doubt become a more important part of pharmaceutical compounding as the public and regulatory agencies demand increasing documentation of the quality of compounded preparations. Compounding pharmacists must decide what types of testing and what amount of testing to include in their quality-control programs, and whether testing should be done in-house or outsourced. Like pharmaceutical compounding, analytical testing should be performed only by those who are appropriately trained and qualified. This article discusses the analytical methods that are used in quality control in a compounding pharmacy. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Features of Pharmaceutical Compounding in the Republic of Tajikistan.

PubMed

Alfred-Ugbenbo, D S; Valiev, A H; Zdoryk, O A; Georgiyants, V A

2017-01-01

Despite the deep assortment of finished pharmaceutical products and the reduction in the number of compounding and hospital pharmacies in the Republic of Tajikistan, the need for extemporal medicinal products is still preserved and remains relevant. This article discusses the practice of compounding in the Republic of Tajikistan. History, laws, limits, regulatory institutions, protocols for compounding pharmacy set up, challenges, equipment, extemporaneous formulations, quality control, and storage within regulatory framework are discussed. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Synthesis and antitumour activity of 4-aminoquinazoline derivatives

NASA Astrophysics Data System (ADS)

Lipunova, G. N.; Nosova, E. V.; Charushin, V. N.; Chupakhin, O. N.

2016-07-01

Pieces of data on the synthesis and antitumour activity of 4-aminoquinazolines are summarized and analyzed. Key methods for the synthesis of these compounds are considered, primarily cyclocondensation of carboxylic acid derivatives, as well as the oxidation of quinazolines and the cyclization of disubstituted thioureas. Improvements of synthetic schemes for erlotinib, gefitinib and lapatinib, which are the best-known pharmaceuticals based on compounds of the title class, are also considered. Synthetic strategies and biological activities for new 4-aminoquinazoline derivatives that are EGFR-tyrosine kinase inhibitors, multiactive compounds, and labelled compounds for use as positron emission tomography (PET) imaging agents are discussed. The bibliography includes 263 references.

Screening and human health risk assessment of pharmaceuticals and their transformation products in Dutch surface waters and drinking water.

PubMed

de Jongh, Cindy M; Kooij, Pascal J F; de Voogt, Pim; ter Laak, Thomas L

2012-06-15

Numerous studies describe the presence of pharmaceuticals in the water cycle, while their transformation products are usually not included. In the current study 17 common pharmaceuticals and 9 transformation products were monitored in the Dutch waters, including surface waters, pre-treated surface waters, river bank filtrates, two groundwater samples affected by surface water and drinking waters. In these samples, 12 pharmaceuticals and 7 transformation products were present. Concentrations were generally highest in surface waters, intermediate in treated surface waters and river bank filtrates and lowest or not detected in produced drinking water. However, the concentrations of phenazone and its environmental transformation product AMPH were significantly higher in river bank filtrates, which is likely due to historical contamination. Fairly constant ratios were observed between concentrations of transformation products and parent pharmaceuticals. This might enable prediction of concentrations of transformation products from concentrations of parent pharmaceuticals. The toxicological relevance of the observed pharmaceuticals and transformation products was assessed by deriving (i) a substance specific provisional guideline value (pGLV) and (ii) a group pGLV for groups of related compounds were under the assumption of additivity of effects within each group. A substantial margin exists between the maximum summed concentrations of these compounds present in different water types and the derived (group) pGLVs. Based on the results of this limited screening campaign no adverse health effects of the studied compounds are expected in (sources of) drinking water in the Netherlands. The presence of transformation products with similar pharmacological activities and concentration levels as their parents illustrates the relevance of monitoring transformation products, and including these in risk assessment. More thorough monitoring yielding information on statistical uncertainty and variability in time and space, and research on possible synergistic effects of low concentration mixtures of compounds belonging to similar pharmacological classes require attention. Copyright © 2012 Elsevier B.V. All rights reserved.

Occurrence and removal of pharmaceuticals and hormones through drinking water treatment.

PubMed

Huerta-Fontela, Maria; Galceran, Maria Teresa; Ventura, Francesc

2011-01-01

The occurrence of fifty-five pharmaceuticals, hormones and metabolites in raw waters used for drinking water production and their removal through a drinking water treatment were studied. Thirty-five out of fifty-five drugs were detected in the raw water at the facility intake with concentrations up to 1200 ng/L. The behavior of the compounds was studied at each step: prechlorination, coagulation, sand filtration, ozonation, granular activated carbon filtration and post-chlorination; showing that the complete treatment accounted for the complete removal of all the compounds detected in raw waters except for five of them. Phenytoin, atenolol and hydrochlorothiazide were the three pharmaceuticals most frequently found in finished waters at concentrations about 10 ng/L. Sotalol and carbamazepine epoxide were found in less than a half of the samples at lower concentrations, above 2 ng/L. However despite their persistence, the removals of these five pharmaceuticals were higher than 95%. Copyright © 2010 Elsevier Ltd. All rights reserved.

Toxicological relevance of pharmaceuticals in drinking water.

PubMed

Bruce, Gretchen M; Pleus, Richard C; Snyder, Shane A

2010-07-15

Interest in the public health significance of trace levels of pharmaceuticals in potable water is increasing, particularly with regard to the effects of long-term, low-dose exposures. To assess health risks and establish target concentrations for water treatment, human health risk-based screening levels for 15 pharmaceutically active ingredients and four metabolites were compared to concentrations detected at 19 drinking water treatment plants across the United States. Compounds were selected based on rate of use, likelihood of occurrence, and potential for toxicity. Screening levels were established based on animal toxicity data and adverse effects at therapeutic doses, focusing largely on reproductive and developmental toxicity and carcinogenicity. Calculated drinking water equivalent levels (DWELs) ranged from 0.49 microg/L (risperidone) to 20,000 microg/L (naproxen). None of the 10 detected compounds exceeded their DWEL. Ratios of DWELs to maximum detected concentrations ranged from 110 (phenytoin) to 6,000,000 (sulfamethoxazole). Based on this evaluation, adverse health effects from targeted pharmaceuticals occurring in U.S. drinking water are not expected.

Microbial Removal of the Pharmaceutical Compounds Ibuprofen and Diclofenac from Wastewater

PubMed Central

Inderfurth, Nadia; Schraa, Gosse; Kujawa-Roeleveld, Katarzyna; Rijnaarts, Huub

2013-01-01

Studies on the occurrence of pharmaceuticals show that the widely used pharmaceuticals ibuprofen and diclofenac are present in relevant concentrations in the environment. A pilot plant treating hospital wastewater with relevant concentrations of these pharmaceuticals was evaluated for its performance to reduce the concentration of the pharmaceuticals. Ibuprofen was completely removed, whereas diclofenac yielded a residual concentration, showing the necessity of posttreatment to remove diclofenac, for example, activated carbon. Successively, detailed laboratory experiments with activated sludge from the same wastewater treatment plant showed bioremediation potential in the treatment plant. The biological degradation pathway was studied and showed a mineralisation of ibuprofen and degradation of diclofenac. The present microbes were further studied in laboratory experiments, and DGGE analyses showed the enrichment and isolation of highly purified cultures that degraded either ibuprofen or diclofenac. This research illuminates the importance of the involved bacteria for the effectiveness of the removal of pharmaceuticals in a wastewater treatment plant. A complete removal of pharmaceuticals from wastewater will stimulate water reuse, addressing the worldwide increasing demand for clean and safe fresh water. PMID:24350260

Carbon Nanomaterials Based Electrochemical Sensors/Biosensors for the Sensitive Detection of Pharmaceutical and Biological Compounds

PubMed Central

Adhikari, Bal-Ram; Govindhan, Maduraiveeran; Chen, Aicheng

2015-01-01

Electrochemical sensors and biosensors have attracted considerable attention for the sensitive detection of a variety of biological and pharmaceutical compounds. Since the discovery of carbon-based nanomaterials, including carbon nanotubes, C60 and graphene, they have garnered tremendous interest for their potential in the design of high-performance electrochemical sensor platforms due to their exceptional thermal, mechanical, electronic, and catalytic properties. Carbon nanomaterial-based electrochemical sensors have been employed for the detection of various analytes with rapid electron transfer kinetics. This feature article focuses on the recent design and use of carbon nanomaterials, primarily single-walled carbon nanotubes (SWCNTs), reduced graphene oxide (rGO), SWCNTs-rGO, Au nanoparticle-rGO nanocomposites, and buckypaper as sensing materials for the electrochemical detection of some representative biological and pharmaceutical compounds such as methylglyoxal, acetaminophen, valacyclovir, β-nicotinamide adenine dinucleotide hydrate (NADH), and glucose. Furthermore, the electrochemical performance of SWCNTs, rGO, and SWCNT-rGO for the detection of acetaminophen and valacyclovir was comparatively studied, revealing that SWCNT-rGO nanocomposites possess excellent electrocatalytic activity in comparison to individual SWCNT and rGO platforms. The sensitive, reliable and rapid analysis of critical disease biomarkers and globally emerging pharmaceutical compounds at carbon nanomaterials based electrochemical sensor platforms may enable an extensive range of applications in preemptive medical diagnostics. PMID:26404304

Behaviour of five pharmaceuticals with high baseline toxicity in wastewater treatment

NASA Astrophysics Data System (ADS)

van Driezum, Inge; McArdell, Christa; Fenner, Kathrin; Helbling, Damian; van Breukelen, Boris

2013-04-01

Many pharmaceuticals enter the aquatic environment through sewer systems and are partially removed in wastewater treatment plants (WWTP) by sorption to sludge biomass or biodegradation. Biodegradation often does not lead to complete mineralization but to the formation of stable transformation products (TPs), which might still be harmful to the environment. Recently, a study was undertaken to assess the risk of the top 100 pharmaceuticals from wastewater of a hospital in Switzerland. The predicted toxicity was linked to the predicted environmental concentration in order to assess overall risk potential. In this study, biodegradation and sorption studies were carried out on the top five selected pharmaceuticals (amiodarone, atorvastatin, clotrimazole, meclozine and ritonavir). Potential TPs that are formed during activated sludge treatment were identified and concentrations of both the parent compounds and TPs were measured in the WWTP. With this data, the fate of these compounds was modeled in a WWTP system using a multi-reactor steady-state WWTP model. This study showed that sorption was the most important loss process for amiodarone and meclozine. They had an elimination of more than 99%. Sorption was also the main loss process for clotrimazole, but it was combined with some biodegradation. For ritonavir, both biodegradation and sorption played a role in the loss of this compound. The most important removal process for atorvastatin was biodegradation. Four TPs, formed through β-oxidation and monohydroxilation, were identified in both the activated sludge batch reactors and the WWTP effluent. In the WWTP effluent, only atorvastatin, clotrimazole and ritonavir were found. All identified TPs of atorvastatin were detected in the effluent. Risk quotients (RQ) of all five pharmaceuticals were estimated based on effluent concentration and baseline toxicity and ranged from zero to 2.14. Only ritonavir potentially poses an ecotoxicological risk for the aquatic environment.

Toxicological and ecotoxicological risk-based prioritization of pharmaceuticals in the natural environment.

PubMed

Guo, Jiahua; Sinclair, Chris J; Selby, Katherine; Boxall, Alistair B A

2016-06-01

Approximately 1500 active pharmaceutical ingredients are currently in use; however, the environmental occurrence and impacts of only a small proportion of these have been investigated. Recognizing that it would be impractical to monitor and assess all pharmaceuticals that are in use, several previous studies have proposed the use of prioritization approaches to identify substances of most concern so that resources can be focused on these. All of these previous approaches suffer from limitations. In the present study, the authors draw on experience from previous prioritization exercises and present a holistic approach for prioritizing pharmaceuticals in the environment in terms of risks to aquatic and soil organisms, avian and mammalian wildlife, and humans. The approach considers both apical ecotoxicological endpoints as well as potential nonapical effects related to the therapeutic mode of action. Application of the approach is illustrated for 146 active pharmaceuticals that are used either in the community or in hospital settings in the United Kingdom. Using the approach, 16 compounds were identified as a potential priority. These substances include compounds belonging to the antibiotic, antidepressant, anti-inflammatory, antidiabetic, antiobesity, and estrogen classes as well as associated metabolites. In the future, the prioritization approach should be applied more broadly around the different regions of the world. Environ Toxicol Chem 2016;35:1550-1559. © 2016 SETAC. © 2016 SETAC.

Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 2. Model prediction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Z.; Peldszus, S.; Huck, P.M.

The adsorption of two representative pharmaceutically active compounds (PhACs) naproxen and carbamazepine and one endocrine disrupting compound (EDC) nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. The GAC adsorbents were coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surfacemore » diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol. 25 refs., 4 figs., 1 tab.« less

Occurrence of Pharmaceuticals in Shallow Ground-Water of Suffolk County, New York, 2002-05

USGS Publications Warehouse

Benotti, Mark J.; Fisher, Shawn; Terracciano, Stephen

2006-01-01

Seventy (70) water samples were collected from 61 wells in the upper glacial and Magothy aquifers (9 wells were sampled twice) during 2002-05 and analyzed for 24 pharmaceuticals. Wells were selected for their proximity to known wastewater-treatment facilities that discharge to the shallow upper glacial aquifer. Pharmaceuticals were detected in 28 of the 70 samples, 19 of which contained one compound, and 9 of which contained two or more compounds. Concentrations of detected compounds were extremely low; most ranged from 0.001 to 0.1 microgram per liter (part per billion). The two most commonly detected compounds were carbamazepine (an antiepileptic drug) and sulfamethoxazole (an antibiotic). Occurrence of pharmaceutical compounds in Suffolk County ground-water is less prevalent than in susceptible streams of the United States that were tested in 1998-2000, but the similarity of median concentrations of the detected compounds of the two data sets indicates that current wastewater practices can serve to introduce pharmaceuticals to this shallow aquifer.

Pharmaceutical compounds in shallow groundwater in non-agricultural areas of Minnesota: study design, methods, and data, 2013

USGS Publications Warehouse

Elliott, Sarah M.; Erickson, Melinda L.

2014-01-01

The U.S. Geological Survey, in cooperation with the Minnesota Pollution Control Agency, completed a study on the occurrence of pharmaceutical compounds and other contaminants of emerging concern in shallow groundwater in non-agricultural areas of Minnesota during 2013. This report describes the study design and methods for the study on the occurrence of pharmaceuticals and other contaminants of emerging concern, and presents the data collected on pharmaceutical compounds. Samples were analyzed by the U.S. Geological Survey National Water Quality Laboratory for 110 pharmaceutical compounds using research method 9017. Samples from 21 of 45 wells had detectable concentrations of at least one of the 110 compounds analyzed. One sample contained detectable concentrations of nine compounds, which was the most detected in a single sample. Fewer than five compounds were detected in most samples. Among all samples, 27 of the 110 compounds were detected in groundwater from at least one well. Desmethyldiltiazem and nicotine were the most frequently detected compounds, each detected in 5 of 46 environmental samples (one well was sampled twice so a total of 46 environmental samples were collected from 45 wells). Caffeine had the highest detectable concentration of all the compounds at 2,060 nanograms per liter.

Method for loading lipsomes with ionizable phosphorylated hydrophobic compounds, pharmaceutical preparations and a method for administering the preparations

DOEpatents

Mehlhorn, Rolf Joachim

1998-10-27

A method of entrapping ionizable compounds, preferably phosphorylated hydrophobic compounds, into liposomes having transmembrane gradients is disclosed. The procedures involve forming liposomes in an acidic medium or a basic medium, adding to the acidic medium a cationic compound or to the basic medium an anionic compound and then adding a base to the cationic-containing medium or an acid to the anionic-containing medium, thereby inducing the ionizable compound into the liposomes' internal aqueous phase. The compound-entrapped liposomes prepared in accordance with the disclosed methods may be used as pharmaceutical preparations. Methods of administering such pharmaceutical preparations are also disclosed.

Compounding in Ukraine.

PubMed

Zdoryk, Oleksandr A; Georgiyants, Victoriya A; Gryzodub, Oleksandr I; Schnatz, Rick

2013-01-01

Pharmaceutical compounding in modern Ukraine has a rich history and goes back to ancient times. Today in the Ukraine, there is a revival of compounding practice, the opening of private compounding pharmacies, updating of legislative framework and requirements of the State Pharmacopeia of Ukraine for compounding preparations, and the introduction of Good Pharmaceutical Practice.

Pharmaceutical products as emerging contaminant in water: relevance for developing nations and identification of critical compounds for Indian environment.

PubMed

Chinnaiyan, Prakash; Thampi, Santosh G; Kumar, Mathava; Mini, K M

2018-04-17

Pharmaceuticals and personal care products (PPCPs) are contaminants of emerging concern and have been detected worldwide in water bodies in trace concentrations. Most of these emerging contaminants are not regulated in water quality standards except a few in the developed countries. In the case of developing countries, research in this direction is at a nascent stage. For the effective management of Pharmaceutical contaminants (PC) in developing countries, the relevance of PCs as an emerging contaminant has to be analyzed followed by regular monitoring of the environment. Considering the resource constraints, this could be accomplished by identifying the priority compounds which is again region specific and dependent on consumption behavior and pattern. In this work, relevance of pharmaceutical compound as emerging contaminant in water for a developing country like India is examined by considering the data pertaining to pharmaceutical consumption data. To identify the critical Pharmaceutical Contaminants to be monitored in the Indian environment, priority compounds from selected prioritization methods were screened with the compounds listed in National List of Essential Medicine (NLEM), India. Further, information on the number of publications on the compound as an emerging contaminant, data on monitoring studies in India and the number of brands marketing the compound in India were also analyzed. It is found that out of 195 compounds from different prioritization techniques, only 77 compounds were found relevant to India based on NLEM sorting.

Investigation of innovative synthesis of biologically active compounds on the basis of newly developed reactions.

PubMed

Honda, Toshio

2012-01-01

Synthesis of biologically active compounds, including natural products and pharmaceutical agents, is an important and interesting research area since the large structural diversity and complexity of bioactive compounds make them an important source of leads and scaffolds in drug discovery and development. Many structurally and also biologically interesting compounds, including marine natural products, have been isolated from nature and have also been prepared on the basis of a computational design for the purpose of developing medicinal chemistry. In order to obtain a wide variety of derivatives of biologically active compounds from the viewpoint of medicinal chemistry, it is essential to establish efficient synthetic procedures for desired targets. Newly developed reactions should also be used for efficient synthesis of desired compounds. Thus, recent progress in the synthesis of biologically active compounds by focusing on the development of new reactions is summarized in this review article.

A natural history of botanical therapeutics

PubMed Central

Schmidt, Barbara; Ribnicky, David M.; Poulev, Alexander; Logendra, Sithes; Cefalu, William T.; Raskin, Ilya

2010-01-01

Plants have been used as a source of medicine throughout history and continue to serve as the basis for many pharmaceuticals used today. Although the modern pharmaceutical industry was born from botanical medicine, synthetic approaches to drug discovery have become standard. However, this modern approach has led to a decline in new drug development in recent years and a growing market for botanical therapeutics that are currently available as dietary supplements, drugs, or botanical drugs. Most botanical therapeutics are derived from medicinal plants that have been cultivated for increased yields of bioactive components. The phytochemical composition of many plants has changed over time, with domestication of agricultural crops resulting in the enhanced content of some bioactive compounds and diminished content of others. Plants continue to serve as a valuable source of therapeutic compounds because of their vast biosynthetic capacity. A primary advantage of botanicals is their complex composition consisting of collections of related compounds having multiple activities that interact for a greater total activity. PMID:18555851

Comparative study on pharmaceuticals adsorption in reclaimed water desalination concentrate using biochar: Impact of salts and organic matter.

PubMed

Lin, Lu; Jiang, Wenbin; Xu, Pei

2017-12-01

The synergistic impact of salts and organic matter on adsorption of ibuprofen and sulfamethoxazole by three types of biochar and an activated carbon was investigated using reclaimed water reverse osmosis (RO) concentrate and synthetic solutions spiked with target organic compounds and non-target water constituents (e.g., Na + , Ca 2+ , Mg 2+ , K + , Cl - , SO 4 2- , alkalinity, humic acid (HA), and bovine serum albumin (BSA)). Kinetic modeling was used to better understand the adsorption process between the carbon adsorbents and pharmaceuticals and to elucidate the impact of water chemistry on pharmaceuticals adsorption. The adsorption capacity of pharmaceuticals by biochar was affected by their physicochemical properties including ash content, specific surface area, charge, pore volume, as well as hydrophobicity, π-energy, and speciation of pharmaceuticals. The adsorption of pharmaceuticals in concentrate was pH-dependent, the kinetic rate constant increased with deceasing pH due to the electrical interactions between pharmaceutical molecules and adsorbents. High salinity and electrolyte ions in RO concentrate improved adsorption, whereas the presence of carbonate species, HA, and BSA hindered the removal of ibuprofen and sulfamethoxazole. This study revealed the correlation of concentrate water quality on adsorption of pharmaceuticals by biochar and activated carbon. Biochar provides a promising alternative to activated carbon for removal of organic contaminants of emerging concerns in various wastewater and concentrate streams. Copyright © 2017 Elsevier B.V. All rights reserved.

Fate and distribution of pharmaceuticals in wastewater and sewage sludge of the conventional activated sludge (CAS) and advanced membrane bioreactor (MBR) treatment.

PubMed

Radjenović, Jelena; Petrović, Mira; Barceló, Damià

2009-02-01

In this paper we report on the performances of full-scale conventional activated sludge (CAS) treatment and two pilot-scale membrane bioreactors (MBRs) in eliminating various pharmaceutically active compounds (PhACs) belonging to different therapeutic groups and with diverse physico-chemical properties. Both aqueous and solid phases were analysed for the presence of 31 pharmaceuticals included in the analytical method. The most ubiquitous contaminants in the sewage water were analgesics and anti-inflammatory drugs ibuprofen (14.6-31.3 microg/L) and acetaminophen (7.1-11.4 microg/L), antibiotic ofloxacin (0.89-31.7 microg/L), lipid regulators gemfibrozil (2.0-5.9 microg/L) and bezafibrate (1.9-29.8 microg/L), beta-blocker atenolol (0.84-2.8 microg/L), hypoglycaemic agent glibenclamide (0.12-15.9 microg/L) and a diuretic hydrochlorothiazide (2.3-4.8 microg/L). Also, several pharmaceuticals such as ibuprofen, ketoprofen, diclofenac, ofloxacin and azithromycin were detected in sewage sludge at concentrations up to 741.1, 336.3, 380.7, 454.7 and 299.6 ng/g dry weight. Two pilot-scale MBRs exhibited enhanced elimination of several pharmaceutical residues poorly removed by the CAS treatment (e.g., mefenamic acid, indomethacin, diclofenac, propyphenazone, pravastatin, gemfibrozil), whereas in some cases more stable operation of one of the MBR reactors at prolonged SRT proved to be detrimental for the elimination of some compounds (e.g., beta-blockers, ranitidine, famotidine, erythromycin). Moreover, the anti-epileptic drug carbamazepine and diuretic hydrochlorothiazide by-passed all three treatments investigated. Furthermore, sorption to sewage sludge in the MBRs as well as in the entire treatment line of a full-scale WWTP is discussed for the encountered analytes. Among the pharmaceuticals encountered in sewage sludge, sorption to sludge could be a relevant removal pathway only for several compounds (i.e., mefenamic acid, propranolol, and loratidine). Especially in the case of loratidine the experimentally determined sorption coefficients (Kds) were in the range 2214-3321 L/kg (mean). The results obtained for the solid phase indicated that MBR wastewater treatment yielding higher biodegradation rate could reduce the load of pollutants in the sludge. Also, the overall output load in the aqueous and solid phase of the investigated WWTP was calculated, indicating that none of the residual pharmaceuticals initially detected in the sewage sludge were degraded during the anaerobic digestion. Out of the 26 pharmaceutical residues passing through the WWTP, 20 were ultimately detected in the treated sludge that is further applied on farmland.

Compounding with Silicones.

PubMed

Allen, Loyd V

2015-01-01

Since the 1940s, methylchlorosilanes have been used to treat glassware to prevent blood from clotting. The use of silicones in pharmaceutical and medical applications has grown to where today they are used in many life-saving devices (pacemakers, hydrocephalic shunts) and pharmaceutical applications from tubing, to excipients in topical formulations, to adhesives to affix transdermal drug delivery systems, and are also being used in products as active pharmaceutical ingredients, such as antiflatulents. About 60% of today's skin-care products now contain some type of silicone where they are considered safe and are known to provide a pleasant "silky-touch," non-greasy, and non-staining feel. Silicones exhibit many useful characteristics, and the safety of these agents supports their numerous applications; their biocompatibility is partially due to their low-chemical reactivity displayed by silicones, low-surface energy, and their hydrophobicity. Silicones are used both as active ingredients and as excipients. In addition is their use for "siliconization," or surface treatment, of many parenteral packaging components. Dimethicone and silicone oil are used as lubricants on stoppers to aid machineability, in syringes to aid piston movement, or on syringe needles to reduce pain upon injection. Silicones are also useful in pharmaceutical compounding as is discussed in this artiele included with this article are in developing formulations with silicones.

Method for loading lipsomes with ionizable phosphorylated hydrophobic compounds, pharmaceutical preparations and a method for administering the preparations

DOEpatents

Mehlhorn, R.J.

1998-10-27

A method of entrapping ionizable compounds, preferably phosphorylated hydrophobic compounds, into liposomes having transmembrane gradients is disclosed. The procedures involve forming liposomes in an acidic medium or a basic medium, adding to the acidic medium a cationic compound or to the basic medium an anionic compound and then adding a base to the cationic-containing medium or an acid to the anionic-containing medium, thereby inducing the ionizable compound into the liposomes` internal aqueous phase. The compound-entrapped liposomes prepared in accordance with the disclosed methods may be used as pharmaceutical preparations. Methods of administering such pharmaceutical preparations are also disclosed. 2 figs.

Physical Approaches to Masking Bitter Taste: Lessons from Food and Pharmaceuticals

PubMed Central

Hayes, John E.

2016-01-01

Many drugs and desirable phytochemicals are bitter, and bitter tastes are aversive. Food and pharmaceutical manufacturers share a common need for bitterness-masking strategies that allow them to deliver useful quantities of the active compounds in an acceptable form and in this review we compare and contrast the challenges and approaches by researchers in both fields. We focus on physical approaches, i.e., micro- or nano-structures to bind bitter compounds in the mouth, yet break down to allow release after they are swallowed. In all of these methods, the assumption is the degree of bitterness suppression depends on the concentration of bitterant in the saliva and hence the proportion that is bound. Surprisingly, this hypothesis has only rarely been fully tested using a combination of adequate human sensory trials and measurements of binding. This is especially true in pharmaceutical systems, perhaps due to the greater experimental challenges in sensory analysis of drugs. PMID:25205460

Recent applications of hydrophilic interaction liquid chromatography in pharmaceutical analysis.

PubMed

Zhang, Qian; Yang, Feng-Qing; Ge, Liya; Hu, Yuan-Jia; Xia, Zhi-Ning

2017-01-01

Hydrophilic interaction liquid chromatography, an alternative liquid chromatography mode, is of particular interest in separating hydrophilic and polar ionic compounds. Compared with traditional liquid chromatography techniques, hydrophilic interaction liquid chromatography offers specific advantages mainly including: (1) relatively green and water-soluble mobile phase composition, which enhances the solubility of hydrophilic and polar ionic compounds; (2) no need for ion-pairing reagents and high content of organic solvent, which benefits mass spectrometry detection; (3) high orthogonality to reverse-phase liquid chromatography, well adapted to two-dimensional liquid chromatography for complicated samples. Therefore, hydrophilic interaction liquid chromatography has been rapidly developed in many areas over the past decades. This review summarizes the recent progress (from 2012 to July 2016) of hydrophilic interaction liquid chromatography in pharmaceutical analysis, with the focus on detecting chemical drugs in various matrices, charactering active compounds of natural products and assessing biotherapeutics through typical structure unit. Moreover, the retention mechanism and behavior of analytes in hydrophilic interaction liquid chromatography as well as some novel hydrophilic interaction liquid chromatography columns used for pharmaceutical analysis are also described. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

40 CFR 439.41 - Special definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... STANDARDS PHARMACEUTICAL MANUFACTURING POINT SOURCE CATEGORY Mixing/Compounding and Formulation § 439.41 Special definitions. For the purpose of this subpart: (a) Mixing, compounding, and formulating operations... product manufactured by blending, mixing, compounding, and formulating pharmaceutical ingredients. The...

Hydroxyalkyl phosphine compounds for use as diagnostic and therapeutic pharmaceuticals

DOEpatents

Katti, K.V.; Singh, P.R.; Reddy, V.S.; Katti, K.K.; Volkert, W.A.; Ketring, A.R.

1999-03-02

This research discloses a compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical comprises a functionalized hydroxyalkyl phosphine ligand and a metal combined with the ligand. 16 figs.

40 CFR 439.41 - Special definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... product manufactured by blending, mixing, compounding, and formulating pharmaceutical ingredients. The... STANDARDS PHARMACEUTICAL MANUFACTURING POINT SOURCE CATEGORY Mixing/Compounding and Formulation § 439.41 Special definitions. For the purpose of this subpart: (a) Mixing, compounding, and formulating operations...

Standard addition method for the determination of pharmaceutical residues in drinking water by SPE-LC-MS/MS.

PubMed

Cimetiere, Nicolas; Soutrel, Isabelle; Lemasle, Marguerite; Laplanche, Alain; Crocq, André

2013-01-01

The study of the occurrence and fate of pharmaceutical compounds in drinking or waste water processes has become very popular in recent years. Liquid chromatography with tandem mass spectrometry is a powerful analytical tool often used to determine pharmaceutical residues at trace level in water. However, many steps may disrupt the analytical procedure and bias the results. A list of 27 environmentally relevant molecules, including various therapeutic classes and (cardiovascular, veterinary and human antibiotics, neuroleptics, non-steroidal anti-inflammatory drugs, hormones and other miscellaneous pharmaceutical compounds), was selected. In this work, a method was developed using ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) and solid-phase extraction to determine the concentration of the 27 targeted pharmaceutical compounds at the nanogram per litre level. The matrix effect was evaluated from water sampled at different treatment stages. Conventional methods with external calibration and internal standard correction were compared with the standard addition method (SAM). An accurate determination of pharmaceutical compounds in drinking water was obtained by the SAM associated with UPLC-MS/MS. The developed method was used to evaluate the occurrence and fate of pharmaceutical compounds in some drinking water treatment plants in the west of France.

Microwave-Assisted Synthesis of Bio-Active Heterocycles and Fine Chemicals in Aqueous Media

EPA Science Inventory

Human health, especially in the aging population, mostly depends on various medicines, and researchers are combating against emerging diseases by new drug discovery. Heterocyclic compounds hold a special place among pharmaceutically active natural products as well as synthetic co...

Biological activities of Agave by-products and their possible applications in food and pharmaceuticals.

PubMed

López-Romero, Julio Cesar; Ayala-Zavala, Jesús Fernando; González-Aguilar, Gustavo Adolfo; Peña-Ramos, Etna Aida; González-Ríos, Humberto

2018-05-01

Agave leaves are considered a by-product of alcoholic beverage production (tequila, mezcal and bacanora) because they are discarded during the production process, despite accounting for approximately 50% of the total plant weight. These by-products constitute a potential source of Agave extracts rich in bioactive compounds, such as saponins, phenolic compounds and terpenes, and possess different biological effects, as demonstrated by in vitro and in vivo tests (e.g. antimicrobial, antifungal, antioxidant, anti-inflammatory, antihypertensive, immunomodulatory, antiparasitic and anticancer activity). Despite their positive results in biological assays, Agave extracts have not been widely evaluated in food systems and pharmaceutical areas, and these fields represent a potential route to improve the usage of Agave plants as food additives and agents for treating medical diseases. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Palladium coupling catalysts for pharmaceutical applications.

PubMed

Doucet, Henri; Hierso, Jean-Cyrille

2007-11-01

This review discusses recent advances made in the area of palladium-catalyzed coupling reactions and describes a selection of the catalytic systems that are useful in the preparation of valuable compounds for the pharmaceutical industry. Most of these types of syntheses have used either simple palladium salts or palladium precursors associated with electron-rich mono- or bidentate phosphine ligands as catalysts. For some reactions, ligands such as triphenyl phosphine, 1,1'-bis(diphenylphosphino)ferrocene, a carbene or a bipyridine have also been employed. Several new procedures for the Suzuki cross-coupling reaction, the activation of aryl chlorides, the functionalization of aromatics and the synthesis of heteroaromatics are discussed. The C-H activation/ functionalization reactions of aryl and heteroaryl derivatives have emerged as powerful tools for the preparation of biaryl compounds, and the recent procedures and catalysts employed in this promising field are also highlighted herein.

Assessment of toxicity and biodegradability on activated sludge of priority and emerging pollutants.

PubMed

Tobajas, Montserrat; Verdugo, Verónica; Polo, Alicia M; Rodriguez, Juan J; Mohedano, Angel F

2016-01-01

Several methods for evaluating the toxicity and biodegradability of hazardous pollutants (chlorinated compounds, chemical additives and pharmaceuticals) have been studied in this work. Different bioassays using representative bacteria of marine and terrestrial ecosystems such as Vibrio fischeri and Pseudomonas putida have been used to assess the ecotoxicity. Activated sludge was used to analyse the effect of those pollutants in a biological reactor of a sewage treatment plant (STP). The results demonstrate that none of the compounds is toxic to activated sludge, except ofloxacin to P. putida. The additives tested can be considered moderately toxic according to the more sensitive V. fischeri assays, whereas the EC50 values of the pharmaceuticals depend on the specific microorganism used in each test. Regarding the biodegradability, respirometric measurements were carried out for fast biodegradability assessment and the Zahn-Wellens test for inherent biodegradability. The evolution of the specific oxygen uptake rate (SOUR) showed that only diethyl phthalate was easily biodegradable and acetylsalicylic acid was partially biodegradable (98% and 65% degradation, respectively). The persistence of dichloromethane, ofloxacin and hidrochlorothiazide was confirmed along the 28 days of the Zahn-Wellens test whereas 1,1,1-trichloroethane showed inherent biodegradability (74% removal). Most of the chlorinated compounds, pharmaceuticals, bisphenol A and ethylenediaminetetraacetic acid were partially degraded in 28 d with total organic carbon (TOC) reduction ranging from 21% to 51%. Sulphamethoxazole showed certain biodegradation (50% removal) with TOC decrease around 31%, which indicates the formation of non-biodegradable by-products.

Prioritizing Environmental Risk of Prescription Pharmaceuticals

PubMed Central

Dong, Zhao; Senn, David B.; Moran, Rebecca E.

2015-01-01

Low levels of pharmaceutical compounds have been detected in aquatic environments worldwide, but their human and ecological health risks associated with low dose environmental exposure is largely unknown due to the large number of these compounds and a lack of information. Therefore prioritization and ranking methods are needed for screening target compounds for research and risk assessment. Previous efforts to rank pharmaceutical compounds have often focused on occurrence data and have paid less attention to removal mechanisms such as human metabolism. This study proposes a simple prioritization approach based on number of prescriptions and toxicity information, accounting for metabolism and wastewater treatment removal, and can be applied to unmeasured compounds. The approach was performed on the 200 most-prescribed drugs in the U.S. in 2009. Our results showed that under-studied compounds such as levothyroxine and montelukast sodium received the highest scores, suggesting the importance of removal mechanisms in influencing the ranking, and the need for future environmental research to include other less-studied but potentially harmful pharmaceutical compounds. PMID:22813724

Identification of Novel Anti-mycobacterial Compounds by Screening a Pharmaceutical Small-Molecule Library against Nonreplicating Mycobacterium tuberculosis.

PubMed

Warrier, Thulasi; Martinez-Hoyos, Maria; Marin-Amieva, Manuel; Colmenarejo, Gonzalo; Porras-De Francisco, Esther; Alvarez-Pedraglio, Ana Isabel; Fraile-Gabaldon, Maria Teresa; Torres-Gomez, Pedro Alfonso; Lopez-Quezada, Landys; Gold, Ben; Roberts, Julia; Ling, Yan; Somersan-Karakaya, Selin; Little, David; Cammack, Nicholas; Nathan, Carl; Mendoza-Losana, Alfonso

2015-12-11

Identification of compounds that target metabolically diverse subpopulations of Mycobacterium tuberculosis (Mtb) may contribute to shortening the course of treatment for tuberculosis. This study screened 270,000 compounds from GlaxoSmithKline's collection against Mtb in a nonreplicating (NR) state imposed in vitro by a combination of four host-relevant stresses. Evaluation of 166 confirmed hits led to detailed characterization of 19 compounds for potency, specificity, cytotoxicity, and stability. Compounds representing five scaffolds depended on reactive nitrogen species for selective activity against NR Mtb, and two were stable in the assay conditions. Four novel scaffolds with activity against replicating (R) Mtb were also identified. However, none of the 19 compounds was active against Mtb in both NR and R states. There was minimal overlap between compounds found active against NR Mtb and those previously identified as active against R Mtb, supporting the hypothesis that NR Mtb depends on distinct metabolic pathways for survival.

Chapter A5. Section 6.1.F. Wastewater, Pharmaceutical, and Antibiotic Compounds

USGS Publications Warehouse

Lewis, Michael Edward; Zaugg, Steven D.

2003-01-01

The USGS differentiates between samples collected for analysis of wastewater compounds and those collected for analysis of pharmaceutical and antibiotic compounds, based on the analytical schedule for the laboratory method. Currently, only the wastewater laboratory method for field-filtered samples (SH1433) is an approved, routine (production) method. (The unfiltered wastewater method LC 8033 also is available but requires a proposal for custom analysis.) At this time, analysis of samples for pharmaceutical and antibiotic compounds is confined to research studies and is available only on a custom basis.

Glycolipids from seaweeds and their potential biotechnological applications.

PubMed

Plouguerné, Erwan; da Gama, Bernardo A P; Pereira, Renato C; Barreto-Bergter, Eliana

2014-01-01

Marine macroalgae, or seaweeds, are a formidable source of natural compounds with diverse biological activities. In the last five decades it has been estimated that more than 3000 natural compounds were discovered from these organisms. The great majority of the published works have focused on terpenoids. In comparison, glycolipids are a neglected class of macroalgal secondary metabolites therefore remaining as a largely unknown reservoir of molecular diversity. Nevertheless, the interest regarding these compounds has been growing fast in the last decades as activities of ecological or pharmaceutical interest have been highlighted. This paper will review recent work regarding isolation and structural characterization of glycolipids from seaweeds and their prospective biological activities.

40 CFR 439.40 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) PHARMACEUTICAL MANUFACTURING POINT SOURCE CATEGORY Mixing/Compounding and Formulation § 439.40... pharmaceutical products by mixing, compounding and formulating operations. [63 FR 50435, Sept. 21, 1998] ...

40 CFR 439.40 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PHARMACEUTICAL MANUFACTURING POINT SOURCE CATEGORY Mixing/Compounding and Formulation § 439.40 Applicability... pharmaceutical products by mixing, compounding and formulating operations. [63 FR 50435, Sept. 21, 1998] ...

40 CFR 439.40 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-07-01

... pharmaceutical products by mixing, compounding and formulating operations. [63 FR 50435, Sept. 21, 1998] ... PHARMACEUTICAL MANUFACTURING POINT SOURCE CATEGORY Mixing/Compounding and Formulation § 439.40 Applicability...

Waste-indicator and pharmaceutical compounds in landfill-leachate-affected ground water near Elkhart, Indiana, 2000-2002.

PubMed

Buszka, P M; Yeskis, D J; Kolpin, D W; Furlong, E T; Zaugg, S D; Meyer, M T

2009-06-01

Four wells downgradient from a landfill near Elkhart, Indiana were sampled during 2000-2002 to evaluate the presence of waste-indicator and pharmaceutical compounds in landfill-leachate-affected ground water. Compounds detected in leachate-affected ground water included detergent metabolites (p-nonylphenol, nonylphenol monoethoxylate, nonylphenol diethoxylate, and octylphenol monoethoxylate), plasticizers (ethanol-2-butoxy-phosphate and diethylphthalate), a plastic monomer (bisphenol A), disinfectants (1,4-dichlorobenzene and triclosan), an antioxidant (5-methyl-1H-benzotriazole), three fire-retardant compounds (tributylphosphate and tri(2-chloroethyl)phosphate, and tri(dichlorisopropyl)phosphate), and several pharmaceuticals and metabolites (acetaminophen, caffeine, cotinine, 1,7-dimethylxanthine, fluoxetine, and ibuprofen). Acetaminophen, caffeine, and cotinine detections confirm prior indications of pharmaceutical and nicotinate disposal in the landfill.

Occurrence of pharmaceutical compounds in wastewater and sludge from wastewater treatment plants: removal and ecotoxicological impact of wastewater discharges and sludge disposal.

PubMed

Martín, J; Camacho-Muñoz, D; Santos, J L; Aparicio, I; Alonso, E

2012-11-15

The occurrence of sixteen pharmaceutically active compounds in influent and effluent wastewater and in primary, secondary and digested sludge in one-year period has been evaluated. Solid-water partition coefficients (Kd) were calculated to evaluate the efficiency of removal of these compounds from wastewater by sorption onto sludge. The ecotoxicological risk to aquatic and terrestrial ecosystems, due to wastewater discharges to the receiving streams and to the application of digested sludge as fertilizer onto soils, was also evaluated. Twelve of the pharmaceuticals were detected in wastewater at mean concentrations from 0.1 to 32 μg/L. All the compounds found in wastewater were also found in sewage sludge, except diclofenac, at mean concentrations from 8.1 to 2206 μg/kg dm. Ibuprofen, salicylic acid, gemfibrozil and caffeine were the compounds at the highest concentrations. LogKd values were between 1.17 (naproxen) and 3.48 (carbamazepine). The highest ecotoxicological risk in effluent wastewater and digested sludge is due to ibuprofen (risk quotient (RQ): 3.2 and 4.4, respectively), 17α-ethinylestradiol (RQ: 12 and 22, respectively) and 17β-estradiol (RQ: 12 and 359, respectively). Ecotoxicological risk after wastewater discharge and sludge disposal is limited to the presence of 17β-estradiol in digested-sludge amended soil (RQ: 2.7). Copyright © 2012 Elsevier B.V. All rights reserved.

Gasification of blended animal manures to produce synthesis gas and activated charcoal

USDA-ARS?s Scientific Manuscript database

Blended swine solids, chicken litter, and hardwood are renewable and expensive sources to produce combined heat and power (CHP), fuels and related chemicals. The therrmochemical pathway to gasify manure has the added advantage of destroying harmful pathogens and pharmaceutically active compounds dur...

Methods for the synthesis of aza(deaza)xanthines as a basis of biologically active compounds

NASA Astrophysics Data System (ADS)

Babkov, D. A.; Geisman, A. N.; Khandazhinskaya, A. L.; Novikov, M. S.

2016-03-01

The review covers methods for the synthesis of aza(deaza)xanthines, i.e., fused pyrrolo-, pyrazolo- and triazolopyrimidine heterocyclic systems, which are common core structures of various biologically active compounds. The extensive range of modern synthetic approaches is organized according to target structures and starting building blocks. The presented material is intended to benefit broad audience of specialists in the fields of organic, medicinal and pharmaceutical chemistry. The bibliography includes 195 references.

Synthesis of lipophilic tyrosyl esters derivatives and assessment of their antimicrobial and antileishmania activities

PubMed Central

2012-01-01

Background Preparation of tyrosyl lipophilic derivatives was carried out as a response to the food, cosmetic and pharmaceutical industries' increasing demand for new lipophilic antioxidants. Results A large series of tyrosyl esters (TyC2 to TyC18:1) with increasing lipophilicity was synthesized in a good yield using lipase from Candida antarctica (Novozyme 435). Spectroscopic analyses of purified esters showed that the tyrosol was esterified on the primary hydroxyl group. Synthetized compounds were evaluated for either their antimicrobial activity, by both diffusion well and minimal inhibition concentration (MIC) methods, or their antileishmanial activity against Leishmania major and Leishmania infantum parasite species. Among all the tested compounds, our results showed that only TyC8, TyC10 and TyC12 exhibited antibacterial and antileishmanial activities. When MIC and IC50 values were plotted against the acyl chain length of each tyrosyl derivative, TyC10 showed a parabolic shape with a minimum value. This nonlinear dependency with the increase of the chain length indicates that biological activities are probably associated to the surfactant effectiveness of lipophilic derivatives. Conclusion These results open up potential applications to use medium tyrosyl derivatives surfactants, antioxidants, antimicrobial and antileishmanial compounds in cosmetic, food and pharmaceutical industries. PMID:22264330

An assessment of the concentrations of pharmaceutical compounds in wastewater treatment plants on the island of Gran Canaria (Spain).

PubMed

Guedes-Alonso, Rayco; Afonso-Olivares, Cristina; Montesdeoca-Esponda, Sarah; Sosa-Ferrera, Zoraida; Santana-Rodríguez, José Juan

2013-12-01

An assessment of the concentrations of thirteen different therapeutic pharmaceutical compounds was conducted on water samples obtained from different wastewater treatment plants (WWTPs) using solid phase extraction and high- and ultra-high-performance liquid chromatography with mass spectrometry detection (HPLC-MS/MS and UHPLC-MS/MS), was carried out. The target compounds included ketoprofen and naproxen (anti-inflammatories), bezafibrate (lipid-regulating), carbamazepine (anticonvulsant), metamizole (analgesic), atenolol (β-blocker), paraxanthine (stimulant), fluoxetine (antidepressant), and levofloxacin, norfloxacin, ciprofloxacin, enrofloxacin and sarafloxacin (fluoroquinolone antibiotics). The relative standard deviations obtained in method were below 11%, while the detection and quantification limits were in the range of 0.3 - 97.4 ng·L(-1) and 1.1 - 324.7 ng·L(-1), respectively. The water samples were collected from two different WWTPs located on the island of Gran Canaria in Spain over a period of one year. The first WWTP (denoted as WWTP1) used conventional activated sludge for the treatment of wastewater, while the other plant (WWTP2) employed a membrane bioreactor system for wastewater treatment. Most of the pharmaceutical compounds detected in this study during the sampling periods were found to have concentrations ranging between 0.02 and 34.81 μg·L(-1).

Efficiency of conventional drinking-water-treatment processes in removal of pharmaceuticals and other organic compounds

USGS Publications Warehouse

Stackelberg, P.E.; Gibs, J.; Furlong, E.T.; Meyer, M.T.; Zaugg, S.D.; Lippincott, R.L.

2007-01-01

Samples of water and sediment from a conventional drinking-water-treatment (DWT) plant were analyzed for 113 organic compounds (OCs) that included pharmaceuticals, detergent degradates, flame retardants and plasticizers, polycyclic aromatic hydrocarbons (PAHs), fragrances and flavorants, pesticides and an insect repellent, and plant and animal steroids. 45 of these compounds were detected in samples of source water and 34 were detected in samples of settled sludge and (or) filter-backwash sediments. The average percent removal of these compounds was calculated from their average concentration in time-composited water samples collected after clarification, disinfection (chlorination), and granular-activated-carbon (GAC) filtration. In general, GAC filtration accounted for 53% of the removal of these compounds from the aqueous phase; disinfection accounted for 32%, and clarification accounted for 15%. The effectiveness of these treatments varied widely within and among classes of compounds; some hydrophobic compounds were strongly oxidized by free chlorine, and some hydrophilic compounds were partly removed through adsorption processes. The detection of 21 of the compounds in 1 or more samples of finished water, and of 3 to 13 compounds in every finished-water sample, indicates substantial but incomplete degradation or removal of OCs through the conventional DWT process used at this plant. ?? 2007 Elsevier B.V. All rights reserved.

Efficiency of conventional drinking-water-treatment processes in removal of pharmaceuticals and other organic compounds.

PubMed

Stackelberg, Paul E; Gibs, Jacob; Furlong, Edward T; Meyer, Michael T; Zaugg, Steven D; Lippincott, R Lee

2007-05-15

Samples of water and sediment from a conventional drinking-water-treatment (DWT) plant were analyzed for 113 organic compounds (OCs) that included pharmaceuticals, detergent degradates, flame retardants and plasticizers, polycyclic aromatic hydrocarbons (PAHs), fragrances and flavorants, pesticides and an insect repellent, and plant and animal steroids. 45 of these compounds were detected in samples of source water and 34 were detected in samples of settled sludge and (or) filter-backwash sediments. The average percent removal of these compounds was calculated from their average concentration in time-composited water samples collected after clarification, disinfection (chlorination), and granular-activated-carbon (GAC) filtration. In general, GAC filtration accounted for 53% of the removal of these compounds from the aqueous phase; disinfection accounted for 32%, and clarification accounted for 15%. The effectiveness of these treatments varied widely within and among classes of compounds; some hydrophobic compounds were strongly oxidized by free chlorine, and some hydrophilic compounds were partly removed through adsorption processes. The detection of 21 of the compounds in 1 or more samples of finished water, and of 3 to 13 compounds in every finished-water sample, indicates substantial but incomplete degradation or removal of OCs through the conventional DWT process used at this plant.

Sorption and toxicity reduction of pharmaceutically active compounds and endocrine disrupting chemicals in the presence of colloidal humic acid.

PubMed

Kim, Injeong; Kim, Hyo-Dong; Jeong, Tae-Yong; Kim, Sang Don

This study investigated the toxicity changes and sorption of pharmaceuticals and endocrine disrupters in the presence of humic acid (HA). For the sorption experiment, a dead end filtration (DEF) system was used to separate bound and free-form target compounds. An algae growth inhibition test and E-screen assay were conducted to estimate the toxic effect of pharmaceutically active compounds (PhACs) and endocrine disrupting chemicals (EDCs), respectively. The permeate concentration was confirmed using liquid chromatography-mass spectrometry. In the sorption test, we observed significant sorption of PhACs and EDCs on colloidal HA, except for sulfamethoxazole (SMX). The values of log KCOC derived from DEF determinations ranged from 4.40 to 5.03. The removal efficiency varied with the HA concentration and the target chemical properties. Tetracycline and 4-octylphenol showed the highest sorption or removal efficiency (≈50%), even at 5 mg C/L HA. The algal growth inhibition of PhACs and the estrogenic effects of EDCs were significantly decreased in proportion to HA concentrations, except for SMX. In addition, the chemical analysis results showed a positive relationship with the bioassay results. Consequently, the sorption of PhACs and EDCs onto colloidal HA should be emphasized in natural environments because it significantly reduces bioavailable concentrations and toxicity to aquatic organisms.

Effects of halogenated aromatics/aliphatics and nitrogen(N)-heterocyclic aromatics on estimating the persistence of future pharmaceutical compounds using a modified QSAR model.

PubMed

Lim, Seung Joo; Fox, Peter

2014-02-01

The effects of halogenated aromatics/aliphatics and nitrogen(N)-heterocyclic aromatics on estimating the persistence of future pharmaceutical compounds were investigated using a modified half life equation. The potential future pharmaceutical compounds investigated were approximately 2000 pharmaceutical drugs currently undergoing the United States Food and Drug Administration (US FDA) testing. EPI Suite (BIOWIN) model estimates the fates of compounds based on the biodegradability under aerobic conditions. While BIOWIN considered the biodegradability of a compound only, the half life equation used in this study was modified by biodegradability, sorption and cometabolic oxidation. It was possible that the potential future pharmaceutical compounds were more accurately estimated using the modified half life equation. The modified half life equation considered sorption and cometabolic oxidation of halogenated aromatic/aliphatics and nitrogen(N)-heterocyclic aromatics in the sub-surface, while EPI Suite (BIOWIN) did not. Halogenated aliphatics in chemicals were more persistent than halogenated aromatics in the sub-surface. In addition, in the sub-surface environment, the fates of organic chemicals were much more affected by halogenation in chemicals than by nitrogen(N)-heterocyclic aromatics. © 2013.

Toxicity challenges in environmental chemicals: Prediction of human plasma protein binding through quantitative structure-activity relationship (QSAR) models

EPA Science Inventory

The present study explores the merit of utilizing available pharmaceutical data to construct a quantitative structure-activity relationship (QSAR) for prediction of the fraction of a chemical unbound to plasma protein (Fub) in environmentally relevant compounds. Independent model...

Prioritizing veterinary pharmaceuticals for aquatic environment in Korea.

PubMed

Kim, Younghee; Jung, Jinyong; Kim, Myunghyun; Park, Jeongim; Boxall, Alistair B A; Choi, Kyungho

2008-09-01

Pharmaceutical residues may have serious impacts on nontarget biological organisms in aquatic ecosystems, and have therefore precipitated numerous investigations worldwide. Many pharmaceutical compounds available on the market need to be prioritized based on their potential ecological and human health risks in order to develop sound management decisions. We prioritized veterinary pharmaceuticals in Korea by their usage, potential to enter the environment, and toxicological hazard. Twenty compounds were identified in the top priority class, most of which were antibiotics. Among these compounds, 8 were identified as deserving more immediate attention: amoxicillin, enramycin, fenbendazole, florfenicol, ivermectin, oxytetracycline, tylosin, and virginiamycin. A limitation of this study is that we initially screened veterinary pharmaceuticals by sales tonnage for veterinary use only. However, this is the first attempt to prioritize veterinary pharmaceuticals in Korea, and it provides important concepts for developing environmental risk management plans for such contaminants in aquatic systems. Copyright © 2008 Elsevier B.V. All rights reserved.

Determination of pharmaceutical compounds in surface- and ground-water samples by solid-phase extraction and high-performance liquid chromatography-electrospray ionization mass spectrometry

USGS Publications Warehouse

Cahill, J.D.; Furlong, E.T.; Burkhardt, M.R.; Kolpin, D.; Anderson, L.G.

2004-01-01

Commonly used prescription and over-the-counter pharmaceuticals are possibly present in surface- and ground-water samples at ambient concentrations less than 1 μg/L. In this report, the performance characteristics of a combined solid-phase extraction isolation and high-performance liquid chromatography–electrospray ionization mass spectrometry (HPLC–ESI-MS) analytical procedure for routine determination of the presence and concentration of human-health pharmaceuticals are described. This method was developed and used in a recent national reconnaissance of pharmaceuticals in USA surface waters. The selection of pharmaceuticals evaluated for this method was based on usage estimates, resulting in a method that contains compounds from diverse chemical classes, which presents challenges and compromises when applied as a single routine analysis. The method performed well for the majority of the 22 pharmaceuticals evaluated, with recoveries greater than 60% for 12 pharmaceuticals. The recoveries of angiotensin-converting enzyme inhibitors, a histamine (H2) receptor antagonist, and antihypoglycemic compound classes were less than 50%, but were retained in the method to provide information describing the potential presence of these compounds in environmental samples and to indicate evidence of possible matrix enhancing effects. Long-term recoveries, evaluated from reagent-water fortifications processed over 2 years, were similar to initial method performance. Method detection limits averaged 0.022 μg/L, sufficient for expected ambient concentrations. Compound-dependent matrix effects on HPLC/ESI-MS analysis, including enhancement and suppression of ionization, were observed as a 20–30% increase in measured concentrations for three compounds and greater than 50% increase for two compounds. Changing internal standard and more frequent ESI source maintenance minimized matrix effects. Application of the method in the national survey demonstrates that several pharmaceuticals are routinely detected at 0.010–0.100 μg/L concentrations.

New approaches with two cyano columns to the separation of acetaminophen, phenylephrine, chlorpheniramine and related compounds.

PubMed

Olmo, B; García, A; Marín, A; Barbas, C

2005-03-25

The development of new pharmaceutical forms with classical active compounds generates new analytical problems. That is the case of sugar-free sachets of cough-cold products containing acetaminophen, phenylephrine hydrochloride and chlorpheniramine maleate. Two cyanopropyl stationary phases have been employed to tackle the problem. The Discovery cyanopropyl (SUPELCO) column permitted the separation of the three actives, maleate and excipients (mainly saccharine and orange flavour) with a constant proportion of aqueous/ organic solvent (95:5, v/v) and a pH gradient from 7.5 to 2. The run lasted 14 min. This technique avoids many problems related to baseline shifts with classical organic solvent gradients and opens great possibilities to modify selectivity not generally used in reversed phase HPLC. On the other hand, the Agilent Zorbax SB-CN column with a different retention profile permitted us to separate not only the three actives and the excipients but also the three known related compounds: 4-aminophenol, 4-chloracetanilide and 4-nitrophenol in an isocratic method with a run time under 30 min. This method was validated following ICH guidelines and validation parameters showed that it could be employed as stability-indicating method for this pharmaceutical form.

Waste-indicator and pharmaceutical compounds in landfill-leachate-affected ground water near Elkhart, Indiana, 2000-2002

USGS Publications Warehouse

Buszka, P.M.; Yeskis, D.J.; Kolpin, D.W.; Furlong, E.T.; Zaugg, S.D.; Meyer, M.T.

2009-01-01

Four wells downgradient from a landfill near Elkhart, Indiana were sampled during 2000-2002 to evaluate the presence of waste-indicator and pharmaceutical compounds in landfill-leachate-affected ground water. Compounds detected in leachate-affected ground water included detergent metabolites (p-nonylphenol, nonylphenol monoethoxylate, nonylphenol diethoxylate, and octylphenol monoethoxylate), plasticizers (ethanol-2-butoxy-phosphate and diethylphthalate), a plastic monomer (bisphenol A), disinfectants (1,4-dichlorobenzene and triclosan), an antioxidant (5-methyl-1H-benzotriazole), three fire-retardant compounds (tributylphosphate and tri(2-chloroethyl)phosphate, and tri(dichlorisopropyl)phosphate), and several pharmaceuticals and metabolites (acetaminophen, caffeine, cotinine, 1,7-dimethylxanthine, fluoxetine, and ibuprofen). Acetaminophen, caffeine, and cotinine detections confirm prior indications of pharmaceutical and nicotinate disposal in the landfill. ?? 2009 Springer Science + Business Media, LLC.

Concentrations of selected pharmaceuticals and antibiotics in south-central Pennsylvania waters, March through September 2006

USGS Publications Warehouse

Loper, Connie A.; Crawford, J. Kent; Otto, Kim L.; Manning, Rhonda L.; Meyer, Michael T.; Furlong, Edward T.

2007-01-01

This report presents environmental and quality-control data from analyses of 15 pharmaceutical and 31 antibiotic compounds in water samples from streams and wells in south-central Pennsylvania. The analyses are part of a study by the U.S. Geological Survey (USGS) in cooperation with the Pennsylvania Department of Environmental Protection (PADEP) to define concentrations of selected emerging contaminants in streams and well water in Pennsylvania. Sampling was conducted at 11 stream sites and at 6 wells in 9 counties of south-central Pennsylvania. Five of the streams received municipal wastewater and 6 of the streams received runoff from agricultural areas dominated by animal-feeding operations. For all 11 streams, samples were collected at locations upstream and downstream of the municipal effluents or animal-feeding operations. All six wells were in agricultural settings. A total of 120 environmental samples and 21 quality-control samples were analyzed for the study. Samples were collected at each site in March/April, May, July, and September 2006 to obtain information on changes in concentration that could be related to seasonal use of compounds.For streams, 13 pharmaceuticals and 11 antibiotics were detected at least 1 time. Detections included analytical results that were estimated or above the minimum reporting limits. Seventy-eight percent of all detections were analyzed in samples collected downstream from municipal-wastewater effluents. For streams receiving wastewater effluents, the pharmaceuticals caffeine and para-xanthine (a degradation product of caffeine) had the greatest concentrations, 4.75 μg/L (micrograms per liter) and 0.853 μg/L, respectively. Other pharmaceuticals and their respective maximum concentrations were carbamazepine (0.516 μg/L) and ibuprofen (0.277 μg/L). For streams receiving wastewater effluents, the antibiotic azithromycin had the greatest concentration (1.65 μg/L), followed by sulfamethoxazole (1.34 μg/L), ofloxacin (0.329 μg/L), and trimethoprim (0.256 μg/L).For streams receiving runoff from animal-feeding operations, the only pharmaceuticals detected were acetaminophen, caffeine, cotinine, diphenhydramine, and carbamazepine. The maximum concentration for pharmaceuticals was 0.053 μg/L. Three streams receiving runoff from animal-feeding operations had detections of one or more antibiotic compound--oxytetracycline, sulfadimethoxine, sulfamethoxazole, and tylosin. The maximum concentration for antibiotics was 0.157 μg/L. The average number of compounds (pharmaceuticals and antibiotics) detected in sites downstream from animal-feeding operations was three. The average number of compounds detected downstream from municipal-wastewater effluents was 13.For wells used to supply livestock, four compounds were detected--two pharmaceuticals (cotinine and diphenhydramine) and two antibiotics (tylosin and sulfamethoxazole). There were five detections in all the well samples. The maximum concentration detected in well water was for cotinine, estimated to be 0.024 μg/L.Seasonal occurrence of pharmaceutical and antibiotic compounds in stream water varied by compound and site type. At four stream sites, the same compounds were detected in all four seasonal samples. At other sites, pharmaceutical or antibiotic compounds were detected only one time in seasonal samples. Winter samples collected in streams receiving municipalwastewater effluent had the greatest number of compounds detected (21). Research analytical methods were used to determine concentrations for pharmaceuticals and antibiotics. To assist in evaluating the quality of the analyses, detailed information is presented on laboratory methodology and results from qualitycontrol samples. Quality-control data include results for nine blanks, nine duplicate environmental sample pairs, and three laboratory-spiked environmental samples as well as the recoveries of compounds in laboratory surrogates and laboratory reagent spikes.

Biological Activity of Ionic Liquids and Their Application in Pharmaceutics and Medicine.

PubMed

Egorova, Ksenia S; Gordeev, Evgeniy G; Ananikov, Valentine P

2017-05-24

Ionic liquids are remarkable chemical compounds, which find applications in many areas of modern science. Because of their highly tunable nature and exceptional properties, ionic liquids have become essential players in the fields of synthesis and catalysis, extraction, electrochemistry, analytics, biotechnology, etc. Apart from physical and chemical features of ionic liquids, their high biological activity has been attracting significant attention from biochemists, ecologists, and medical scientists. This Review is dedicated to biological activities of ionic liquids, with a special emphasis on their potential employment in pharmaceutics and medicine. The accumulated data on the biological activity of ionic liquids, including their antimicrobial and cytotoxic properties, are discussed in view of possible applications in drug synthesis and drug delivery systems. Dedicated attention is given to a novel active pharmaceutical ingredient-ionic liquid (API-IL) concept, which suggests using traditional drugs in the form of ionic liquid species. The main aim of this Review is to attract a broad audience of chemical, biological, and medical scientists to study advantages of ionic liquid pharmaceutics. Overall, the discussed data highlight the importance of the research direction defined as "Ioliomics", studies of ions in liquids in modern chemistry, biology, and medicine.

Activated carbon for the removal of pharmaceutical residues from treated wastewater.

PubMed

Ek, Mats; Baresel, Christian; Magnér, Jörgen; Bergström, Rune; Harding, Mila

2014-01-01

Pharmaceutical residues, which pass naturally through the human body into sewage, are in many cases virtually unaffected by conventional wastewater treatment. Accumulated in the environment, however, they can significantly impact aquatic life. The present study indicates that many pharmaceutical residues found in wastewater can be removed with activated carbon in a cost-efficient system that delivers higher resource utilisation and security than other carbon systems. The experiment revealed a substantial separation of the analysed compounds, notwithstanding their relatively high solubility in water and dissimilar chemical structures. This implies that beds of activated carbon may be a competitive alternative to treatment with ozone. The effluent water used for the tests, performed over 20 months, originated from Stockholm's largest sewage treatment plant. Passing through a number of different filters with activated carbon removed 90-98% of the pharmaceutical residues from the water. This paper describes pilot-scale tests performed by IVL and the implications for an actual treatment plant that has to treat up to several thousand litres of wastewater per second. In addition, the advantages, disadvantages and costs of the method are discussed. This includes, for example, the clogging of carbon filters and the associated hydraulic capacity limits of the activated carbon.

Assessment of the anaerobic degradation of six active pharmaceutical ingredients.

PubMed

Musson, Stephen E; Campo, Pablo; Tolaymat, Thabet; Suidan, Makram; Townsend, Timothy G

2010-04-01

Research examined the anaerobic degradation of 17 alpha-ethynylestradiol, acetaminophen, acetylsalicylic acid, ibuprofen, metoprolol tartrate, and progesterone by methanogenic bacteria. Using direct sample analysis and respirometric testing, anaerobic degradation was examined with (a) each compound as the sole organic carbon source and (b) each compound at a lower concentration (250 microg/L) and cellulose serving as the primary organic carbon source. The change in pharmaceutical concentration was determined following 7, 28, 56, and 112 days of anaerobic incubation at 37 degrees C. Only acetylsalicylic acid demonstrated significant degradation; the remaining compounds showed a mixture of degradation and abiotic removal mechanisms. Experimental results were compared with BIOWIN, an anaerobic degradation prediction model of the US Environmental Protection Agency. The BIOWIN model predicted anaerobic biodegradability of the compounds in the order: acetylsalicylic acid > metoprolol tartrate > ibuprofen > acetaminophen > 17 alpha-ethinylestradiol >progesterone. This corresponded well with the experimental findings which found degradability in the order: acetylsalicylic acid > metoprolol tartrate > acetaminophen > ibuprofen. (c) 2010 Elsevier B.V. All rights reserved.

Non-invasive method for quantitative evaluation of exogenous compound deposition on skin.

PubMed

Stamatas, Georgios N; Wu, Jeff; Kollias, Nikiforos

2002-02-01

Topical application of active compounds on skin is common to both pharmaceutical and cosmetic industries. Quantification of the concentration of a compound deposited on the skin is important in determining the optimum formulation to deliver the pharmaceutical or cosmetic benefit. The most commonly used techniques to date are either invasive or not easily reproducible. In this study, we have developed a noninvasive alternative to these techniques based on spectrofluorimetry. A mathematical model based on diffusion approximation theory is utilized to correct fluorescence measurements for the attenuation caused by endogenous skin chromophore absorption. The limitation is that the compound of interest has to be either fluorescent itself or fluorescently labeled. We used the method to detect topically applied salicylic acid. Based on the mathematical model a calibration curve was constructed that is independent of endogenous chromophore concentration. We utilized the method to localize salicylic acid in epidermis and to follow its dynamics over a period of 3 d.

Green coffee seed residue: A sustainable source of antioxidant compounds.

PubMed

Castro, A C C M; Oda, F B; Almeida-Cincotto, M G J; Davanço, M G; Chiari-Andréo, B G; Cicarelli, R M B; Peccinini, R G; Zocolo, G J; Ribeiro, P R V; Corrêa, M A; Isaac, V L B; Santos, A G

2018-04-25

Oil extraction from green coffee seeds generates residual mass that is discarded by agribusiness and has not been previously studied. Bioactive secondary metabolites in coffee include antioxidant phenolic compounds, such as chlorogenic acids. Coffee seeds also contain caffeine, a pharmaceutically important methylxanthine. Here, we report the chemical profile, antioxidant activity, and cytotoxicity of hydroethanolic extracts of green Coffea arabica L. seed residue. The extracts of the green seeds and the residue have similar chemical profiles, containing the phenolic compounds chlorogenic acid and caffeine. Five monoacyl and three diacyl esters of trans-cinnamic acids and quinic acid were identified by ultra-performance liquid chromatography/electrospray ionization-quadruple time of flight mass spectrometry. The residue extract showed antioxidant potential in DPPH, ABTS, and pyranine assays and low cytotoxicity. Thus, coffee oil residue has great potential for use as a raw material in dietary supplements, cosmetic and pharmaceutical products, or as a source of bioactive compounds. Copyright © 2017. Published by Elsevier Ltd.

Charting Biologically Relevant Spirocyclic Compound Space.

PubMed

Müller, Gerhard; Berkenbosch, Tim; Benningshof, Jorg C J; Stumpfe, Dagmar; Bajorath, Jürgen

2017-01-12

Spirocycles frequently occur in natural products and experience increasing interest in drug discovery, given their richness in sp 3 centers and distinct three-dimensionality. We have systematically explored chemical space populated with currently available bioactive spirocycles. Compounds containing spiro systems were classified and their scaffolds and spirocyclic ring combinations analyzed. Nearly 47 000 compounds were identified that contained spirocycles in different structural contexts and were active against roughly 200 targets, among which several pharmaceutically relevant members of the G protein-coupled receptor (GPCR) family were identified. Spirocycles and corresponding compounds displayed notable scaffold diversity but contained only limited numbers of combinations of differently sized rings. These observations indicate that there should be significant potential to further expand spirocyclic chemical space for drug discovery, exploiting the privileged substructure concept. Inspired by those findings, we embarked on the design and chemical synthesis of three distinct novel spirocyclic scaffolds that qualify for downstream library synthesis, thus exploring principally new chemical space with high potential for pharmaceutical research. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds.

PubMed

Delfosse, Vanessa; Dendele, Béatrice; Huet, Tiphaine; Grimaldi, Marina; Boulahtouf, Abdelhay; Gerbal-Chaloin, Sabine; Beucher, Bertrand; Roecklin, Dominique; Muller, Christina; Rahmani, Roger; Cavaillès, Vincent; Daujat-Chavanieu, Martine; Vivat, Valérie; Pascussi, Jean-Marc; Balaguer, Patrick; Bourguet, William

2015-09-03

Humans are chronically exposed to multiple exogenous substances, including environmental pollutants, drugs and dietary components. Many of these compounds are suspected to impact human health, and their combination in complex mixtures could exacerbate their harmful effects. Here we demonstrate that a pharmaceutical oestrogen and a persistent organochlorine pesticide, both exhibiting low efficacy when studied separately, cooperatively bind to the pregnane X receptor, leading to synergistic activation. Biophysical analysis shows that each ligand enhances the binding affinity of the other, so the binary mixture induces a substantial biological response at doses at which each chemical individually is inactive. High-resolution crystal structures reveal the structural basis for the observed cooperativity. Our results suggest that the formation of 'supramolecular ligands' within the ligand-binding pocket of nuclear receptors contributes to the synergistic toxic effect of chemical mixtures, which may have broad implications for the fields of endocrine disruption, toxicology and chemical risk assessment.

Tracing pharmaceuticals in a municipal plant for integrated wastewater and organic solid waste treatment.

PubMed

Jelic, Aleksandra; Fatone, Francesco; Di Fabio, Silvia; Petrovic, Mira; Cecchi, Franco; Barcelo, Damia

2012-09-01

The occurrence and removal of 42 pharmaceuticals, belonging to different therapeutic groups (analgesics and anti-inflammatory drugs, anti-ulcer agent, psychiatric drugs, antiepileptic drug, antibiotics, ß-blockers, diuretics, lipid regulator and cholesterol lowering statin drugs and anti-histamines), were studied in the wastewater and sewage sludge trains of a full scale integrated treatment plant. The plant employs a biological nutrient removal (BNR) process for the treatment of municipal wastewater, and a single-stage mesophilic anaerobic co-digestion for the treatment of wasted activated sludge mixed with the organic fraction of municipal solid waste (OFMSW), followed by a short-cut nitrification-denitrification of the anaerobic supernatant in a sequential batch reactor. Influent and effluent wastewater, as well as thickened, digested and treated sludge were sampled and analyzed for the selected pharmaceuticals in order to study their presence and fate during the treatment. Twenty three compounds were detected in influent and effluent wastewater and eleven in sludge. Infiltration of groundwater in the sewer system led to a dilution of raw sewage, resulting in lower concentrations in wastewater (up to 0.7 μg/L in influent) and sludge (70 ng/g d.w.). Due to the dilution, overall risk quotient for the mixture of pharmaceuticals detected in effluent wastewater was less than one, indicating no direct risk for the aquatic environment. A wide range of removal efficiencies during the treatment was observed, i.e. <20% to 90%. The influent concentrations of the target pharmaceuticals, as polar compounds, were undoubtedly mostly affected by BNR process in the wastewater train, and less by anaerobic-co-digestion. Mass balance calculations showed that less than 2% of the total mass load of the studied pharmaceuticals was removed by sorption. Experimentally estimated distribution coefficients (<500 L/kg) also indicated that the selected pharmaceuticals preferably remain in the aqueous phase, and that biodegradation/transformation is the primary removal mechanism for these compounds during wastewater treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

Antioxidant, Antimicrobial Effects and Phenolic Profile of Lycium barbarum L. Flowers.

PubMed

Mocan, Andrei; Vlase, Laurian; Vodnar, Dan Cristian; Gheldiu, Ana-Maria; Oprean, Radu; Crișan, Gianina

2015-08-17

L. barbarum L. is a widely-accepted nutraceutical presenting highly advantageous nutritive and antioxidant properties. Its flowers have been previously described as a source of diosgenin, β-sitosterol and lanosterol that can be further pharmaceutically developed, but no other data regarding their composition is available. The purpose of this work was to investigate the chemical constituents, antioxidant and antimicrobial activities of L. barbarum flowers, as an alternative resource of naturally-occurring antioxidant compounds. The free radical scavenging activity of the ethanolic extract was tested by TEAC, two enzymatic assays with more physiological relevance and EPR spectroscopy. The presence of several phenolic compounds, such as chlorogenic, p-coumaric and ferulic acids, but also isoquercitrin, rutin and quercitrin, was assessed by an HPLC/MS method. The antioxidant assays revealed that the extract exhibited a moderate antioxidant potential. The antimicrobial activity was mild against Gram-positive bacteria and lacking against Escherichia coli. These findings complete the scarce existing data and offer new perspectives for further pharmaceutical valorization of L. barbarum flowers.

Marine actinobacteria: an important source of bioactive natural products.

PubMed

Manivasagan, Panchanathan; Kang, Kyong-Hwa; Sivakumar, Kannan; Li-Chan, Eunice C Y; Oh, Hyun-Myung; Kim, Se-Kwon

2014-07-01

Marine environment is largely an untapped source for deriving actinobacteria, having potential to produce novel, bioactive natural products. Actinobacteria are the prolific producers of pharmaceutically active secondary metabolites, accounting for about 70% of the naturally derived compounds that are currently in clinical use. Among the various actinobacterial genera, Actinomadura, Actinoplanes, Amycolatopsis, Marinispora, Micromonospora, Nocardiopsis, Saccharopolyspora, Salinispora, Streptomyces and Verrucosispora are the major potential producers of commercially important bioactive natural products. In this respect, Streptomyces ranks first with a large number of bioactive natural products. Marine actinobacteria are unique enhancing quite different biological properties including antimicrobial, anticancer, antiviral, insecticidal and enzyme inhibitory activities. They have attracted global in the last ten years for their ability to produce pharmaceutically active compounds. In this review, we have focused attention on the bioactive natural products isolated from marine actinobacteria, possessing unique chemical structures that may form the basis for synthesis of novel drugs that could be used to combat resistant pathogenic microorganisms. Copyright © 2014 Elsevier B.V. All rights reserved.

Natural Product Potential of the Genus Nocardiopsis

PubMed Central

Ibrahim, Alyaa Hatem; Desoukey, Samar Yehia; Fouad, Mostafa A.; Kamel, Mohamed Salah; Gulder, Tobias A. M.; Abdelmohsen, Usama Ramadan

2018-01-01

Actinomycetes are a relevant source of novel bioactive compounds. One of the pharmaceutically and biotechnologically important genera that attract natural products research is the genus Nocardiopsis, mainly for its ability to produce a wide variety of secondary metabolites accounting for its wide range of biological activities. This review covers the literature from January 2015 until February 2018 making a complete survey of all the compounds that were isolated from the genus Nocardiopsis, their biological activities, and natural sources, whenever applicable. PMID:29710816

Hydroxymethyl phosphine compounds for use as diagnostic and therapeutic pharmaceuticals and method of making same

DOEpatents

Katti, Kattesh V.; Karra, Srinivasa Rao; Berning, Douglas E.; Smith, C. Jeffrey; Volkert, Wynn A.; Ketring, Alan R.

1999-01-01

A compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical comprises at least one functionalized hydroxyalkyl phosphine donor group and one or more sulfur or nitrogen donor and a metal combined with the ligand.

Hydroxymethyl phosphine compounds for use as diagnostic and therapeutic pharmaceuticals and method of making same

DOEpatents

Katti, Kattesh V.; Karra, Srinivasa Rao; Berning, Douglas E.; Smith, C. Jeffrey; Volkert, Wynn A.; Ketring, Alan R.

2000-01-01

A compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical comprises at least one functionalized hydroxyalkyl phosphine donor group and one or more sulfur or nitrogen donor and a metal combined with the ligand.

Exploring Marine Cyanobacteria for Lead Compounds of Pharmaceutical Importance

PubMed Central

Uzair, Bushra; Tabassum, Sobia; Rasheed, Madiha; Rehman, Saima Firdous

2012-01-01

The Ocean, which is called the “mother of origin of life,” is also the source of structurally unique natural products that are mainly accumulated in living organisms. Cyanobacteria are photosynthetic prokaryotes used as food by humans. They are excellent source of vitamins and proteins vital for life. Several of these compounds show pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immunodeficiency syndrome (AIDS), arthritis, and so forth, while other compounds have been developed as analgesics or to treat inflammation, and so forth. They produce a large variety of bioactive compounds, including substances with anticancer and antiviral activity, UV protectants, specific inhibitors of enzymes, and potent hepatotoxins and neurotoxins. Many cyanobacteria produce compounds with potent biological activities. This paper aims to showcase the structural diversity of marine cyanobacterial secondary metabolites with a comprehensive coverage of alkaloids and other applications of cyanobacteria. PMID:22545008

A Randomized, Double-Blind, Placebo-Controlled Crossover Study of the Anti-Inflammatory Compound Anatabine to Treat Pain in GWI Patients

DTIC Science & Technology

2016-10-01

inflammation. Over the last few years we have carried out extensive work on the dietary supplement Anatabine (Rock Creek Pharmaceuticals Inc.), which is a...minor adverse effects reported. Anatabine products are no longer available as dietary supplements as the compound company is pursuing pharmaceutical use...compound, which was available from Rock Creek Pharmaceuticals (RCP) for several years (2010-2014) as a dietary supplement . It is no longer being sold as a

Gamma irradiation improves the antioxidant activity of Aloe vera (Aloe barbadensis miller) extracts

NASA Astrophysics Data System (ADS)

Mi Lee, Eun; Bai, Hyoung-Woo; Sik Lee, Seung; Hyun Hong, Sung; Cho, Jae-Young; Yeoup Chung, Byung

2012-08-01

Aloe has been widely used in food products, pharmaceuticals, and cosmetics because of its aromatic and therapeutic properties. In the present study, the ethanolic extracts of aloe gel were gamma-irradiated from 10 to 100 kGy. After gamma irradiation, the color of the ethanolic extracts of aloe gel changed to red; this color persisted up to 40 kGy but disappeared above 50 kGy. Liquid chromatography/mass spectrometry analysis demonstrated the production of a new, unknown compound (m/z=132) after gamma irradiation of the ethanolic extracts of aloe gel. The amount of this unknown compound increased with increasing irradiation up to 80 kGy, and it was degraded at 100 kGy. Interestingly, it was found that gamma irradiation significantly increased the antioxidant activity, as measured by the 1,1-diphenyl-2-picrylhydrazyl-radical scavenging capacity. The antioxidant activity of aloe extract was dramatically increased from 53.9% in the non-irradiated sample to 92.8% in the sample irradiated at 40 kGy. This strong antioxidant activity was retained even at 100 kGy. These results indicate that gamma irradiation of aloe extract can enhance its antioxidant activity through the formation of a new compound. Based on these results, increased antioxidant activity of aloe extracts by gamma rays can be applied to various industries, especially cosmetics, foodstuffs, and pharmaceuticals.

Pharmacology Risk Report

NASA Technical Reports Server (NTRS)

2010-01-01

It seems very likely that the actions of administered drugs on crewmembers during spaceflight are different than they are on Earth, but even after more than 40 years of spaceflight experience, the answers to most questions about medication use during missions remain unanswered. Use of medications with insufficient knowledge about their actual activities may result in inadequate treatment and may even reduce performance and well-being in particular circumstances. There is evidence that this has already occurred during and immediately after spaceflights. The spaceflight pharmaceutical activity knowledge base must be improved to enable flight surgeons and crewmembers to make better decisions about using pharmaceuticals inflight. The spaceflight environment induces changes in human physiology, and these changes have been the subject of much study over the past few decades. These studies are confounded by the small number of potential subjects, as well by the inability to separate the different stressors of spaceflight (radiation exposure from microgravity, for example). In every physiological system, the details of spaceflight-induced physiological changes are not well understood. Despite this fact, crewmembers are treated with pharmaceuticals to reduce or prevent medical problems, with insufficient information as to drug function on their altered physiological systems. There are two major concerns about pharmaceutical use in the unusual environment of spaceflight. The actions of pharmaceuticals on physiology altered by a spaceflight environment are currently assumed to be the same as the actions in terrestrial use. This has yet to be established. The wide range of physiological systems altered by spaceflight and the degree of change experienced in some of them make it very likely that alterations in pharmaceutical action will be seen. As the duration of missions lengthens to include more distant exploration, it becomes more likely that problems will be encountered. Secondly, the integrity of stored pharmaceuticals must be established to ensure that adequate amounts of active compounds are available in each dose and that degradation to toxic compounds is minimized. This risk is also dependent on mission duration, since longer missions will require that drugs be stored much longer than their usual terrestrial shelf-lives.

Household Disposal of Pharmaceuticals as a Pathway for Aquatic Contamination in the United Kingdom

PubMed Central

Bound, Jonathan P.; Voulvoulis, Nikolaos

2005-01-01

Pharmaceuticals are produced and used in increasingly large volumes every year. With this growth comes concern about the fate and effects of these compounds in the environment. The discovery of pharmaceuticals in the aquatic environment has stimulated research in the last decade. A wide range of pharmaceuticals has been found in fresh and marine waters, and it has recently been shown that even in small quantities, some of these compounds have the potential to cause harm to aquatic life. The primary pathway into the environment is the use and disposal of medicines; although much of the research in the area currently focuses on the removal of pharmaceuticals during sewage treatment processes, disposal via household waste might be a significant pathway requiring further research. To investigate the household disposal of unused and expired pharmaceuticals as a source of pharmaceutical compounds in the environment, we carried out a survey and interviewed members of 400 households, predominantly from southeastern England. We used the information on when and how they disposed of unfinished pharmaceuticals to construct a conceptual model to assess the pathways of human pharmaceuticals into the environment. The model demonstrated that disposal of unused pharmaceuticals, either by household waste or via the sink or toilet, may be a prominent route that requires greater attention. PMID:16330351

Therapeutic potential and health benefits of Sargassum species

PubMed Central

Yende, Subhash R.; Harle, Uday N.; Chaugule, Bhupal B.

2014-01-01

Sargassum species are tropical and sub-tropical brown macroalgae (seaweed) of shallow marine meadow. These are nutritious and rich source of bioactive compounds such as vitamins, carotenoids, dietary fibers, proteins, and minerals. Also, many biologically active compounds like terpenoids, flavonoids, sterols, sulfated polysaccharides, polyphenols, sargaquinoic acids, sargachromenol, pheophytine were isolated from different Sargassum species. These isolated compounds exhibit diverse biological activities like analgesic, anti-inflammatory, antioxidant, neuroprotective, anti-microbial, anti-tumor, fibrinolytic, immune-modulatory, anti-coagulant, hepatoprotective, anti-viral activity etc., Hence, Sargassum species have great potential to be used in pharmaceutical and neutralceutical areas. This review paper explores the current knowledge of phytochemical, therapeutic potential, and health benefits of different species of genus Sargassum. PMID:24600190

Hydroxymethyl phosphine compounds for use as diagnostic and therapeutic pharmaceuticals and method of making same

DOEpatents

Katti, K.V.; Karra, S.R.; Berning, D.E.; Smith, C.J.; Volkert, W.A.; Ketring, A.R.

1999-01-05

A compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical comprises at least one functionalized hydroxyalkyl phosphine donor group and one or more sulfur or nitrogen donor and a metal combined with the ligand. 21 figs.

Occurrence and potential transport of selected pharmaceuticals and other organic wastewater compounds from wastewater-treatment plant influent and effluent to groundwater and canal systems in Miami-Dade County, Florida

USGS Publications Warehouse

Foster, Adam L.; Katz, Brian G.; Meyer, Michael T.

2012-01-01

An increased demand for fresh groundwater resources in South Florida has prompted Miami-Dade County to expand its water reclamation program and actively pursue reuse plans for aquifer recharge, irrigation, and wetland rehydration. The U.S. Geological Survey, in cooperation with the Miami-Dade Water and Sewer Department (WASD) and the Miami-Dade Department of Environmental Resources Management (DERM), initiated a study in 2008 to assess the presence of selected pharmaceuticals and other organic wastewater compounds in the influent and effluent at three regional wastewater-treatment plants (WWTPs) operated by the WASD and at one WWTP operated by the City of Homestead, Florida (HSWWTP).

Occurrence and removal of pharmaceutically active compounds in sewage treatment plants with different technologies

USGS Publications Warehouse

Ying, Guang-Guo; Kookana, Rai S.; Kolpin, Dana W.

2009-01-01

Occurrence of eight selected pharmaceutically active compounds (PhACs; caffeine, carbamazepine, triclosan, gemfibrozil, diclofenac, ibuprofen, ketoprofen and naproxen) were investigated in effluents from fifteen sewage treatment plants (STPs) across South Australia. In addition, a detailed investigation into the removal of these compounds was also carried out in four STPs with different technologies (Plant A: conventional activated sludge; plant B: two oxidation ditches; plant C: three bioreactors; and plant D: ten lagoons in series). The concentrations of these compounds in the effluents from the fifteen STPs showed substantial variations among the STPs, with their median concentrations ranging from 26 ng/L for caffeine to 710 ng/L for carbamazepine. Risk assessment based on the "worst case scenario" of the monitoring data from the present study suggested potential toxic risks to aquatic organisms posed by carbamazepine, triclosan and diclofenac associated with such effluent discharge. With the exception of carbamazepine and gemfibrozil, significant concentration decreases between influent and effluent were observed in the four STPs studied in more detail. Biodegradation was found to be the main mechanism for removing concentrations from the liquid waste stream for the PhACs within the four STPs, while adsorption onto sludge appeared to be a minor process for all target PhACs except for triclosan. Some compounds (e.g. gemfibrozil) exhibited variable removal efficiencies within the four STPs. Plant D (10 lagoons in series) was least efficient in the removal of the target PhACs; significant biodegradation of these compounds only occurred from the sixth or seventh lagoon.

Occurrence and removal of pharmaceutically active compounds in sewage treatment plants with different technologies.

PubMed

Ying, Guang-Guo; Kookana, Rai S; Kolpin, Dana W

2009-08-01

Occurrence of eight selected pharmaceutically active compounds (PhACs; caffeine, carbamazepine, triclosan, gemfibrozil, diclofenac, ibuprofen, ketoprofen and naproxen) were investigated in effluents from fifteen sewage treatment plants (STPs) across South Australia. In addition, a detailed investigation into the removal of these compounds was also carried out in four STPs with different technologies (Plant A: conventional activated sludge; plant B: two oxidation ditches; plant C: three bioreactors; and plant D: ten lagoons in series). The concentrations of these compounds in the effluents from the fifteen STPs showed substantial variations among the STPs, with their median concentrations ranging from 26 ng/L for caffeine to 710 ng/L for carbamazepine. Risk assessment based on the "worst case scenario" of the monitoring data from the present study suggested potential toxic risks to aquatic organisms posed by carbamazepine, triclosan and diclofenac associated with such effluent discharge. With the exception of carbamazepine and gemfibrozil, significant concentration decreases between influent and effluent were observed in the four STPs studied in more detail. Biodegradation was found to be the main mechanism for removing concentrations from the liquid waste stream for the PhACs within the four STPs, while adsorption onto sludge appeared to be a minor process for all target PhACs except for triclosan. Some compounds (e.g. gemfibrozil) exhibited variable removal efficiencies within the four STPs. Plant D (10 lagoons in series) was least efficient in the removal of the target PhACs; significant biodegradation of these compounds only occurred from the sixth or seventh lagoon.

Biotransformation and adsorption of pharmaceutical and personal care products by activated sludge after correcting matrix effects.

PubMed

Deng, Yu; Li, Bing; Yu, Ke; Zhang, Tong

2016-02-15

This study reported significant suppressive matrix effects in analyses of six pharmaceutical and personal care products (PPCPs) in activated sludge, sterilized activated sludge and untreated sewage by ultra-performance liquid chromatography-tandem mass spectrometry. Quantitative matrix evaluation on selected PPCPs supplemented the limited quantification data of matrix effects on mass spectrometric determination of PPCPs in complex environment samples. The observed matrix effects were chemical-specific and matrix-dependent, with the most pronounced average effect (-55%) was found on sulfadiazine in sterilized activated sludge. After correcting the matrix effects by post-spiking known amount of PPCPs, the removal mechanisms and biotransformation kinetics of selected PPCPs in activated sludge system were revealed by batch experiment. Experimental data elucidated that the removal of target PPCPs in the activated sludge process was mainly by biotransformation while contributions of adsorption, hydrolysis and volatilization could be neglected. High biotransformation efficiency (52%) was observed on diclofenac while other three compounds (sulfadiazine, sulfamethoxazole and roxithromycin) were partially biotransformed by ~40%. The other two compounds, trimethoprim and carbamazepine, showed recalcitrant to biotransformation of the activated sludge. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthetic biology approaches in drug discovery and pharmaceutical biotechnology.

PubMed

Neumann, Heinz; Neumann-Staubitz, Petra

2010-06-01

Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology.

Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Welberry, T.R.; Chan, E.J.; Goossens, D.J.

Polymorphism occurs when the same molecular compound can crystallize in more than one distinct crystal structure. Its study is a field of great interest and activity. This is largely driven by its importance in the pharmaceutical industry, but polymorphism is also an issue in the pigments, dyes, and explosives industries. The polymorph formed by a compound generally exerts a strong influence on its solid-state properties. The polymorphic form of a drug molecule may affect the ease of manufacture and processing, shelf life, and most significantly the rate of uptake of the molecule by the human body. They can even varymore » in toxicity; one polymorph may be safe, while a second may be toxic. In this review of recently published work, we show how diffuse scattering experiments coupled with Monte Carlo (MC) computer modeling can aid in the understanding of polymorphism. Examples of the two common pharmaceuticals, benzocaine and aspirin, both of which are bimorphic, at ambient temperatures, are discussed.« less

Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals

NASA Astrophysics Data System (ADS)

Welberry, T. R.; Chan, E. J.; Goossens, D. J.; Heerdegen, A. P.

2012-05-01

Polymorphism occurs when the same molecular compound can crystallize in more than one distinct crystal structure. Its study is a field of great interest and activity. This is largely driven by its importance in the pharmaceutical industry, but polymorphism is also an issue in the pigments, dyes, and explosives industries. The polymorph formed by a compound generally exerts a strong influence on its solid-state properties. The polymorphic form of a drug molecule may affect the ease of manufacture and processing, shelf life, and most significantly the rate of uptake of the molecule by the human body. They can even vary in toxicity; one polymorph may be safe, while a second may be toxic. In this review of recently published work, we show how diffuse scattering experiments coupled with Monte Carlo (MC) computer modeling can aid in the understanding of polymorphism. Examples of the two common pharmaceuticals, benzocaine and aspirin, both of which are bimorphic, at ambient temperatures, are discussed.

Analysis and advanced oxidation treatment of a persistent pharmaceutical compound in wastewater and wastewater sludge-carbamazepine.

PubMed

Mohapatra, D P; Brar, S K; Tyagi, R D; Picard, P; Surampalli, R Y

2014-02-01

Pharmaceutically active compounds (PhACs) are considered as emerging environmental problem due to their continuous input and persistence to the aquatic ecosystem even at low concentrations. Among them, carbamazepine (CBZ) has been detected at the highest frequency, which ends up in aquatic systems via wastewater treatment plants (WWTPs) among other sources. The identification and quantification of CBZ in wastewater (WW) and wastewater sludge (WWS) is of major interest to assess the toxicity of treated effluent discharged into the environment. Furthermore, WWS has been subjected for re-use either in agricultural application or for the production of value-added products through the route of bioconversion. However, this field application is disputable due to the presence of these organic compounds and in order to protect the ecosystem or end users, data concerning the concentration, fate, behavior as well as the perspective of simultaneous degradation of these compounds is urgently necessary. Many treatment technologies, including advanced oxidation processes (AOPs) have been developed in order to degrade CBZ in WW and WWS. AOPs are technologies based on the intermediacy of hydroxyl and other radicals to oxidize recalcitrant, toxic and non-biodegradable compounds to various by-products and eventually to inert end products. The purpose of this review is to provide information on persistent pharmaceutical compound, carbamazepine, its ecological effects and removal during various AOPs of WW and WWS. This review also reports the different analytical methods available for quantification of CBZ in different contaminated media including WW and WWS. © 2013 Elsevier B.V. All rights reserved.

SANIST: optimization of a technology for compound identification based on the European Union directive with applications in forensic, pharmaceutical and food analyses.

PubMed

Cristoni, Simone; Dusi, Guglielmo; Brambilla, Paolo; Albini, Adriana; Conti, Matteo; Brambilla, Maura; Bruno, Antonino; Di Gaudio, Francesca; Ferlin, Luca; Tazzari, Valeria; Mengozzi, Silvia; Barera, Simone; Sialer, Carlos; Trenti, Tommaso; Cantu, Marco; Rossi Bernardi, Luigi; Noonan, Douglas M

2017-01-01

Electrospray Ionization and collision induced dissociation tandem mass spectrometry are usually employed to obtain compound identification through a mass spectra match. Different algorithms have been developed for this purpose (for example the nist match algorithm). These approaches compare the tandem mass spectra of the unknown analyte with the tandem mass spectra spectra of known compounds inserted in a database. The compounds are usually identified on the basis of spectral match value associated with a probability of recognition. However, this approach is not usually applied to multiple reaction monitoring transition spectra achieved by means of triple quadrupole apparatus, mainly due to the lack of a transition spectra database. The Surface Activated Chemical Ionization-Electrospray-NIST Bayesian model database search (SANIST) platform has been recently developed for new potential metabolite biomarker discovery, to confirm their identity and to use them for clinical and diagnostic applications. Here, we present an improved version of the SANIST platform that extends its application to forensic, pharmaceutical, and food analysis studies, where the compound identification rules are strict. The European Union (EU) has set directives for compound identification (EU directive 2002/657/EC). We have applied the SANIST method to identification of 11-nor-9-carboxytetrahydro-cannabinol in urine samples (an example of a forensic application), circulating levels of the immunosuppressive drug tacrolimus in blood (an example of a pharmaceutical application) and glyphosate in fruit juice (an example of a food analysis application) that meet the EU directive requirements. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

In vitro antimicrobial activity of extracts and isolated compound from Dalbergia stipulacea Roxb. leaves

NASA Astrophysics Data System (ADS)

Kumar, Arvind; Bhat, Tahir Ahmad; Singh, Rattan Deep

2017-07-01

The study was designed to examine the in vitro antimicrobial efficacy of extracts and isolated compound of Dalbergia stipulacea. Combined extracts (chloroform and methanol) of plant leaves fractionated with n-butanol loaded with column afforded a flavonoid glycoside compound identified as luteolin 4'-rutinoside. Different extracts and isolated compound exhibited pronounced antibacterial and antifungal varied activities against four bacteria (Clostridium acetobutylinium, Bacillus subtilis, Streptococcus mutans, and Pseudomonas sp.) and one fungus (Candida albicans) susceptibility were determined using disc diffusion method. The minimum inhibitory concentration (MIC) of extracts and isolated compounds was determined by broth dilution method. The maximum activity was shown by chloroform extract against C. albicans with a zone of inhibition of 17 mm and minimum activity was displayed by methanolic extract against Pseudomonas sp. with 5 mm. However, isolated compound has shown maximum activity against Pseudomonas sp. with 15 mm. The MIC values higher in methanol extract against Pseudomonas sp. and isolated compound shows good against Pseudomonas sp. and B. subtilis. Our findings indicate that plant could be used as a good antimicrobial agent in food, pharmaceutical and bio-pesticide industries.

How efficient are constructed wetlands in removing pharmaceuticals from untreated and treated urban wastewaters? A review.

PubMed

Verlicchi, Paola; Zambello, Elena

2014-02-01

This review presents and discusses the data from 47 peer-reviewed journal articles on the occurrence of 137 pharmaceutical compounds in the effluent from various types of constructed wetlands treating urban wastewater. We analyse the observed removal efficiencies of the investigated compounds in order to identify the type of constructed wetland that best removes those most frequently detected. The literature reviewed details experimental investigations carried out on 136 treatment plants, including free water surface systems, as well as horizontal and vertical subsurface flow beds (pilot or full-scale) acting as primary, secondary or tertiary treatments. The occurrence of selected pharmaceuticals in sediments and gravel and their uptake by common macrophytes are also presented and discussed. We analyse the main removal mechanisms for the selected compounds and investigate the influence of the main design parameters, as well as operational and environmental conditions of the treatment systems on removal efficiency. We also report on previous attempts to correlate observed removal values with the chemical structure and chemical-physical properties (mainly pKa and LogKow) of pharmaceutical compounds. We then use the literature data to calculate the average pharmaceutical mass loadings in the effluent from constructed wetlands, comparing the ability of such systems to remove selected pharmaceuticals with the corresponding conventional secondary and tertiary treatments. Finally, the environmental risk posed by pharmaceutical residues in effluents from constructed wetlands acting as secondary and tertiary treatment steps is calculated in the form of the risk quotient ratio. This approach enabled us to provide a ranking of the most critical compounds for the two scenarios, to discuss the ramifications of the adoption of constructed wetlands for removing such persistent organic compounds, and to propose avenues of future research. © 2013.

A successful virtual screening application: prediction of anticonvulsant activity in MES test of widely used pharmaceutical and food preservatives methylparaben and propylparaben.

PubMed

Talevi, Alan; Bellera, Carolina L; Castro, Eduardo A; Bruno-Blanch, Luis E

2007-09-01

A discriminant function based on topological descriptors was derived from a training set composed by anticonvulsants of clinical use or in clinical phase of development and compounds with other therapeutic uses. This model was internally and externally validated and applied in the virtual screening of chemical compounds from the Merck Index 13th. Methylparaben (Nipagin), a preservative widely used in food, cosmetics and pharmaceutics, was signaled as active by the discriminant function and tested in mice in the Maximal Electroshock (MES) test (i.p. administration), according to the NIH Program for Anticonvulsant Drug Development. Based on the results of Methylparaben, Propylparaben (Nipasol), another preservative usually used in association with the former, was also tested. Both methyl and propylparaben were found active in mice at doses of 30, 100, and 300 mg/kg. The discovery of the anticonvulsant activities in the MES test of methylparaben and propylparaben might be useful for the development of new anticonvulsant medications, specially considering the well-known toxicological profile of these drugs.

A successful virtual screening application: prediction of anticonvulsant activity in MES test of widely used pharmaceutical and food preservatives methylparaben and propylparaben

NASA Astrophysics Data System (ADS)

Talevi, Alan; Bellera, Carolina L.; Castro, Eduardo A.; Bruno-Blanch, Luis E.

2007-09-01

A discriminant function based on topological descriptors was derived from a training set composed by anticonvulsants of clinical use or in clinical phase of development and compounds with other therapeutic uses. This model was internally and externally validated and applied in the virtual screening of chemical compounds from the Merck Index 13th. Methylparaben (Nipagin), a preservative widely used in food, cosmetics and pharmaceutics, was signaled as active by the discriminant function and tested in mice in the Maximal Electroshock (MES) test (i.p. administration), according to the NIH Program for Anticonvulsant Drug Development. Based on the results of Methylparaben, Propylparaben (Nipasol), another preservative usually used in association with the former, was also tested. Both methyl and propylparaben were found active in mice at doses of 30, 100, and 300 mg/kg. The discovery of the anticonvulsant activities in the MES test of methylparaben and propylparaben might be useful for the development of new anticonvulsant medications, specially considering the well-known toxicological profile of these drugs.

PHARMACEUTICALS AND PERSONAL CARE PRODUCTS ...

EPA Pesticide Factsheets

While the point-source emissions of pollutants from manufacturing waste streams have long been monitored and subject to controls, the environmental impact of the public's (i.e., the individual's) activities regarding the use of chemicals is more difficult to assess. Of particular question is the widespread release to sewage and surface/ground waters of pharmaceuticals and personal care products after their ingestion, external application, or disposal. Certain pharmaceutically active compounds (e.g., caffeine, nicotine, and aspirin) have been known for over 20 years to enter the environment by a variety of routes - primarily via treated and untreated sewage effluent. A larger picture, however, has emerged only more recently, where it is evident that numerous personal care products (such as fragrances and sunscreens) and drugs from a wide spectrum of therapeutic classes can occur in the environment and drinking water (albeit at very low concentrations), especially in natural waters receiving sewage. Nearly all ecological monitoring studies for pharmaceuticals and personal care products (informally referred to as

Investigation of pharmaceuticals in Missouri natural and drinking water using high performance liquid chromatography-tandem mass spectrometry.

PubMed

Wang, Chuan; Shi, Honglan; Adams, Craig D; Gamagedara, Sanjeewa; Stayton, Isaac; Timmons, Terry; Ma, Yinfa

2011-02-01

A comprehensive method has been developed and validated in two different water matrices for the analysis of 16 pharmaceutical compounds using solid phase extraction (SPE) of water samples, followed by liquid chromatography coupled with tandem mass spectrometry. These 16 compounds include antibiotics, hormones, analgesics, stimulants, antiepileptics, and X-ray contrast media. Method detection limits (MDLs) that were determined in both reagent water and municipal tap water ranged from 0.1 to 9.9 ng/L. Recoveries for most of the compounds were comparable to those obtained using U.S. EPA methods. Treated and untreated water samples were collected from 31 different water treatment facilities across Missouri, in both winter and summer seasons, and analyzed to assess the 16 pharmaceutical compounds. The results showed that the highest pharmaceutical concentrations in untreated water were caffeine, ibuprofen, and acetaminophen, at concentrations of 224, 77.2, and 70 ng/L, respectively. Concentrations of pharmaceuticals were generally higher during the winter months, as compared to those in the summer due, presumably, to smaller water quantities in the winter, even though pharmaceutical loadings into the receiving waters were similar for both seasons. © 2010 Elsevier Ltd. All rights reserved.

Comparison of Rheological and Sedimentation Behavior of Commercially Available Suspending Vehicles for Oral Pharmaceutical Preparations.

PubMed

Visser, J Carolina; Ten Seldam, Inge E J; van der Linden, Isabella J; Hinrichs, Wouter L J; Veenendaal, Reinier F H; Dijkers, Eli C F; Woerdenbag, Herman J

2018-01-01

A pharmaceutical suspension is a semi-liquid dosage form suitable for patients being unable to swallow solid medicines such as tablets and capsules. A vehicle used for the preparation of pharmaceutical oral suspensions preferably shows pseudo-plastic behavior. In a product that gets thinner with agitation and thicker upon standing, slow settlement of the suspended active pharmaceutical ingredient is combined with good pourability and rehomogenization. This gives the best guarantee of uniformity of dose for oral suspensions. In this study, the rheological behavior of commercially available ready-to-use vehicles for oral pharmaceutical preparations was compared, and the sedimentation of paracetamol dispersed in these vehicles was investigated. With SuspendIt and SyrSpend SF PH4 (Liquid), both pseudoplastic vehicles, very stable paracetamol suspensions were obtained. Of these two vehicles, SyrSpend SF PH4 (Liquid) displayed somewhat higher viscosity, which is a favorable quality characteristic for suspensions. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Evaluation of a Novel Approach for Reducing Emissions of Pharmaceuticals to the Environment

NASA Astrophysics Data System (ADS)

Bean, Thomas G.; Bergstrom, Ed; Thomas-Oates, Jane; Wolff, Amy; Bartl, Peter; Eaton, Bob; Boxall, Alistair B. A.

2016-10-01

Increased interest over the levels of pharmaceuticals detected in the environment has led to the need for new approaches to manage their emissions. Inappropriate disposal of unused and waste medicines and release from manufacturing plants are believed to be important pathways for pharmaceuticals entering the environment. In situ treatment technologies, which can be used on-site in pharmacies, hospitals, clinics, and at manufacturing plants, might provide a solution. In this study we explored the use of Pyropure, a microscale combined pyrolysis and gasification in situ treatment system for destroying pharmaceutical wastes. This involved selecting 17 pharmaceuticals, including 14 of the most thermally stable compounds currently in use and three of high environmental concern to determine the technology's success in waste destruction. Treatment simulation studies were done on three different waste types and liquid, solid, and gaseous emissions from the process were analyzed for parent pharmaceutical and known active transformation products. Gaseous emissions were also analyzed for NOx, particulates, dioxins, furans, and metals. Results suggest that Pyropure is an effective treatment process for pharmaceutical wastes: over 99 % of each study pharmaceutical was destroyed by the system without known active transformation products being formed during the treatment process. Emissions of the other gaseous air pollutants were within acceptable levels. Future uptake of the system, or similar in situ treatment approaches, by clinics, pharmacists, and manufacturers could help to reduce the levels of pharmaceuticals in the environment and reduce the economic and environmental costs of current waste management practices.

Pharmaceutically active secondary metabolites of marine actinobacteria.

PubMed

Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

2014-04-01

Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future. Copyright © 2013 Elsevier GmbH. All rights reserved.

Bioinformatics: Cheap and robust method to explore biomaterial from Indonesia biodiversity

NASA Astrophysics Data System (ADS)

Widodo

2015-02-01

Indonesia has a huge amount of biodiversity, which may contain many biomaterials for pharmaceutical application. These resources potency should be explored to discover new drugs for human wealth. However, the bioactive screening using conventional methods is very expensive and time-consuming. Therefore, we developed a methodology for screening the potential of natural resources based on bioinformatics. The method is developed based on the fact that organisms in the same taxon will have similar genes, metabolism and secondary metabolites product. Then we employ bioinformatics to explore the potency of biomaterial from Indonesia biodiversity by comparing species with the well-known taxon containing the active compound through published paper or chemical database. Then we analyze drug-likeness, bioactivity and the target proteins of the active compound based on their molecular structure. The target protein was examined their interaction with other proteins in the cell to determine action mechanism of the active compounds in the cellular level, as well as to predict its side effects and toxicity. By using this method, we succeeded to screen anti-cancer, immunomodulators and anti-inflammation from Indonesia biodiversity. For example, we found anticancer from marine invertebrate by employing the method. The anti-cancer was explore based on the isolated compounds of marine invertebrate from published article and database, and then identified the protein target, followed by molecular pathway analysis. The data suggested that the active compound of the invertebrate able to kill cancer cell. Further, we collect and extract the active compound from the invertebrate, and then examined the activity on cancer cell (MCF7). The MTT result showed that the methanol extract of marine invertebrate was highly potent in killing MCF7 cells. Therefore, we concluded that bioinformatics is cheap and robust way to explore bioactive from Indonesia biodiversity for source of drug and another pharmaceutical material.

Factors affecting the dissipation of pharmaceuticals in freshwater sediments.

PubMed

Al-Khazrajy, Omar S A; Bergström, Ed; Boxall, Alistair B A

2018-03-01

Degradation is one of the key processes governing the impact of pharmaceuticals in the aquatic environment. Most studies on the degradation of pharmaceuticals have focused on soil and sludge, with fewer exploring persistence in aquatic sediments. We investigated the dissipation of 6 pharmaceuticals from different therapeutic classes in a range of sediment types. Dissipation of each pharmaceutical was found to follow first-order exponential decay. Half-lives in the sediments ranged from 9.5 (atenolol) to 78.8 (amitriptyline) d. Under sterile conditions, the persistence of pharmaceuticals was considerably longer. Stepwise multiple linear regression analysis was performed to explore the relationships between half-lives of the pharmaceuticals, sediment physicochemical properties, and sorption coefficients for the compounds. Sediment clay, silt, and organic carbon content and microbial activity were the predominant factors related to the degradation rates of diltiazem, cimetidine, and ranitidine. Regression analysis failed to highlight a key property which may be responsible for observed differences in the degradation of the other pharmaceuticals. The present results suggest that the degradation rate of pharmaceuticals in sediments is determined by different factors and processes and does not exclusively depend on a single sediment parameter. Environ Toxicol Chem 2018;37:829-838. © 2017 SETAC. © 2017 SETAC.

Consumer Chemistry in the Classroom. Science from the Supermarket.

ERIC Educational Resources Information Center

Sumrall, William J.; Brown, Fred W.

1991-01-01

Activities that show students a practical use for chemistry using common items such as food products, pharmaceuticals, and household products as sources of chemical compounds are presented. The importance of having adequate resource materials available for students is emphasized. (KR)

Tyrosine-like condensed derivatives as tyrosinase inhibitors.

PubMed

Matos, Maria João; Santana, Lourdes; Uriarte, Eugenio; Serra, Silvia; Corda, Marcella; Fadda, Maria Benedetta; Era, Benedetta; Fais, Antonella

2012-05-01

We report the pharmacological evaluation of a new series of 3-aminocoumarins differently substituted with hydroxyl groups, which have been synthesized because they include in their structures the tyrosine fragment (tyrosine-like compounds), with the aim of discovering structural features necessary for tyrosinase inhibitory activity. The synthesized compounds 4 and 7-9 were evaluated in vitro as mushroom tyrosinase inhibitors. Two of the described compounds showed lower IC50 (concentration giving 50% inhibition of tyrosinase activity) than umbelliferone, used as a reference compound. Compound 7 (IC50=53µm) was the best tyrosinase inhibitor of this small series, having an IC50 value 10-fold lower than umbelliferone. Compound 7 (3-amino-7-hydroxycoumarin) had amino and hydroxyl groups precisely mimicking the same positions that both groups occupy on the tyrosine molecule. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Influence of naturally occurring dissolved organic matter, colloids, and cations on nanofiltration of pharmaceutically active and endocrine disrupting compounds.

PubMed

Sadmani, A H M Anwar; Andrews, Robert C; Bagley, David M

2014-12-01

This study examined the rejection of selected pharmaceutically active (PhAC) and endocrine disrupting compounds (EDCs) when using nanofiltration as a function of naturally occurring dissolved organic matter (DOM), colloidal particles, cations and their interactions. Lake Ontario water served as a source of natural DOM and colloidal particles. PhAC/EDC rejection experiments were conducted using raw Lake Ontario water and Lake Ontario water that was pre-treated with either ultrafiltration to remove colloidal particles, or fluidized ion exchange resins to remove DOM. Additionally, the concentration of cations (Ca(2+), Mg(2+), and Na(+)) in the raw and pre-treated water matrices was varied. While ionic PhACs and EDCs exhibited high rejections from all the water matrices examined, neutral compounds were most effectively rejected in water containing DOM and no colloids, and least effectively rejected from colloid-containing water with increased cations but no DOM. The presence of DOM significantly improved compound rejection and the increase in cation concentration significantly decreased rejection. The presence of colloids had comparatively little effect except to mitigate the impact of increased cation concentration, apparently providing some cation-buffering capacity. The sequence in which constituents are removed from waters during treatment may significantly impact PhAC and EDC removal, especially of neutral compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications

PubMed Central

Vardanyan, Ruben S; Hruby, Victor J

2014-01-01

Fentanyl and its analogs have been mainstays for the treatment of severe to moderate pain for many years. In this review, we outline the structural and corresponding synthetic strategies that have been used to understand the structure–biological activity relationship in fentanyl-related compounds and derivatives and their biological activity profiles. We discuss how changes in the scaffold structure can change biological and pharmacological activities. Finally, recent efforts to design and synthesize novel multivalent ligands that act as mu and delta opioid receptors and NK-1 receptors are discussed. PMID:24635521

Pharmaceuticals as Groundwater Tracers - Applications and Limitations

NASA Astrophysics Data System (ADS)

Scheytt, T. J.; Mersmann, P.; Heberer, T.

2003-12-01

Pharmaceutically active substances and metabolites are found at concentrations up to the microgram/L-level in groundwater samples from the Berlin (Germany) area and from several other places world wide. Among the compounds detected in groundwater are clofibric acid, propyphenazone, diclofenac, ibuprofen, and carbamazepine. Clofibric acid, the active metabolite of clofibrate and etofibrate (blood lipid regulators) is detected in groundwater at maximum concentrations of 7300 ng/L. Among the most important input paths of drugs are excretion and disposal into the sewage system. Groundwater contamination is likely to be due to leaky sewage systems, influent streams, bank filtration, and irrigation with effluent water from sewage treatment plants. There are no known natural sources of the above mentioned pharmaceuticals. The use of pharmaceuticals as tracers may include: (a) Quantification of infiltration from underground septic tanks (b) Detection of leaky sewage systems / leaky sewage pipes (c) Estimation of the effectiveness of sewage treatment plants (d) Identification of transport pathways of other organic compounds (e) Quantification of surface water / groundwater interaction (f) Characterization of the biodegradation potential. The use of pharmaceuticals as tracers is limited by variations in input. These variations depend on the amount of drugs prescribed and used in the study area, the social structure of the community, the amount of hospital discharge, and temporal concentration variations. Furthermore, the analysis of trace amounts of pharmaceuticals is sophisticated and expensive and may therefore limit the applicability of pharmaceuticals as tracers. Finally, the transport and degradation behavior of pharmaceuticals is not fully understood. Preliminary experiments in the laboratory were conducted using sediment material and groundwater from the Berlin area to evaluate the transport and sorption behavior of selected drugs. Results of the column experiments show that clofibric acid exhibits no degradation and almost no retardation (Rf = 1.1) whereas ibuprofen is biodegraded (> 90 %) under aerobic conditions. Carbamazepine shows no degradation in the soil column experiments but significant retardation under the prevailing conditions. We conclude that clofibric acid will show the transport behavior of a conservative tracer, whereas ibuprofen may be used to characterize the biodegradation potential in the aerobic zone.

Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action †

PubMed Central

Mayer, Alejandro M. S.; Rodríguez, Abimael D.; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

2013-01-01

The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009–2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories. PMID:23880931

Emerging contaminants in Belgian marine waters: single toxicant and mixture risks of pharmaceuticals.

PubMed

Claessens, Michiel; Vanhaecke, Lynn; Wille, Klaas; Janssen, Colin R

2013-06-15

Knowledge on the effects of pharmaceuticals on aquatic marine ecosystems is limited. The aim of this study was therefore to establish the effect thresholds of pharmaceutical compounds occurring in the Belgian marine environment for the marine diatom Phaeodactylum tricornutum, and subsequently perform an environmental risk assessment for these substances. Additionally, a screening-level risk assessment was performed for the pharmaceutical mixtures. No immediate risk for acute toxic effects of these compounds on P. tricornutum were apparent at the concentrations observed in the Belgian marine environment. In two Belgian coastal harbours however, a potential chronic risk was observed for the β-blocker propranolol. No additional risks arising from the exposure to mixtures of pharmaceuticals present in the sampling area could be detected. However, as risk characterization ratios for mixtures of up to 0.5 were observed, mixture effects could emerge should more compounds be taken into account. Copyright © 2013 Elsevier Ltd. All rights reserved.

Occurrence and seasonal variations of 25 pharmaceutical residues in wastewater and drinking water treatment plants.

PubMed

Kot-Wasik, A; Jakimska, A; Śliwka-Kaszyńska, M

2016-12-01

Thousands of tons of pharmaceuticals are introduced into the aqueous environment due to their incomplete elimination during treatment process in wastewater treatment plants (WWTPs) and water treatment plants (WTPs). The presence of pharmacologically active compounds in the environment is of a great interest because of their potential to cause negative effects. Furthermore, drugs can undergo different processes leading to the formation of new transformation products, which may be more toxic than the parent compound. In light of these concerns, within the research a new, rapid and sensitive analytical procedure for the determination of a wide range of pharmaceuticals from different classes using solid phase extraction (SPE) and high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) technique in different water samples was developed. This methodology was applied to investigate the occurrence, removal efficiency of 25 pharmaceuticals during wastewater and drinking water treatment, and seasonal variability in the amount of selected pharmaceuticals in WWTP and WTP over a year. The most often detected analytes in water samples were carbamazepine (100 % of samples) and ibuprofen (98 % of samples), concluding that they may be considered as pollution indicators of the aqueous environment in tested area. Highly polar compound, metformin, was determined at very high concentration level of up to 8100 ng/L in analyzed water samples. Drugs concentrations were much higher in winter season, especially for non-steroidal inflammatory drugs (NSAIDs) and caffeine, probably due to the inhibited degradation related to lower temperatures and limited sunlight. Carbamazepine was found to be the most resistant drug to environmental degradation and its concentrations were at similar levels during four seasons.

Compound Structure-Independent Activity Prediction in High-Dimensional Target Space.

PubMed

Balfer, Jenny; Hu, Ye; Bajorath, Jürgen

2014-08-01

Profiling of compound libraries against arrays of targets has become an important approach in pharmaceutical research. The prediction of multi-target compound activities also represents an attractive task for machine learning with potential for drug discovery applications. Herein, we have explored activity prediction in high-dimensional target space. Different types of models were derived to predict multi-target activities. The models included naïve Bayesian (NB) and support vector machine (SVM) classifiers based upon compound structure information and NB models derived on the basis of activity profiles, without considering compound structure. Because the latter approach can be applied to incomplete training data and principally depends on the feature independence assumption, SVM modeling was not applicable in this case. Furthermore, iterative hybrid NB models making use of both activity profiles and compound structure information were built. In high-dimensional target space, NB models utilizing activity profile data were found to yield more accurate activity predictions than structure-based NB and SVM models or hybrid models. An in-depth analysis of activity profile-based models revealed the presence of correlation effects across different targets and rationalized prediction accuracy. Taken together, the results indicate that activity profile information can be effectively used to predict the activity of test compounds against novel targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Compounds, compositions, pharmaceutical compositions, and methods of use

DOEpatents

Hammond, Gerald B.; Jin, Zhuang; Bates, Paula J.; Reyes-Reyes, Elsa Merit

2016-11-15

Certain embodiments of the invention include compositions comprising a compound of Formula (I), and salts, isomers, and derivatives thereof. Pharmaceutical compositions of some embodiments of the present invention comprise a compound of Formula (I), and salts, isomers, and derivatives thereof. Other embodiments of this invention include methods for treating disease (e.g., cancer) and methods for administering a compound of Formula (I), and salts, isomers, and derivatives thereof.

Adsorption of pharmaceuticals onto trimethylsilylated mesoporous SBA-15.

PubMed

Bui, Tung Xuan; Pham, Viet Hung; Le, Son Thanh; Choi, Heechul

2013-06-15

The adsorption of a complex mixture of 12 selected pharmaceuticals to trimethylsilylated mesoporous SBA-15 (TMS-SBA-15) has been investigated by batch adsorption experiments. The adsorption of pharmaceuticals to TMS-SBA-15 was highly dependent on the solution pH and pharmaceutical properties (i.e., hydrophobicity (logKow) and acidity (pKa)). Good log-log linear relationships between the adsorption (Kd) and pH-dependent octanol-water coefficients (Kow(pH)) were then established among the neutral, anionic, and cationic compounds, suggesting hydrophobic interaction as a primary driving force in the adsorption. In addition, the neutral species of each compound accounted for a major contribution to the overall compound adsorption onto TMS-SBA-15. The adsorption kinetics of pharmaceuticals was evaluated by the nonlinear first-order and pseudo-second-order models. The first-order model gave a better fit for five pharmaceuticals with lower adsorption capacity, whereas the pseudo-second-order model fitted better for seven pharmaceuticals having higher adsorption capacity. In the same group of properties, pharmaceuticals having higher adsorption capacity exhibited faster adsorption rates. The rate-limiting steps for adsorption of pharmaceuticals onto TMS-SBA-15 are boundary layer diffusion and intraparticle diffusion including diffusion in mesopores and micropores. In addition, the adsorption of pharmaceuticals to TMS-SBA-15 was not influenced by the change of initial pharmaceutical concentration (10-100μgL(-1)) and the presence of natural organic matter. Copyright © 2013 Elsevier B.V. All rights reserved.

Classification of the crystallization behavior of amorphous active pharmaceutical ingredients in aqueous environments.

PubMed

Van Eerdenbrugh, Bernard; Raina, Shweta; Hsieh, Yi-Ling; Augustijns, Patrick; Taylor, Lynne S

2014-04-01

To classify the crystallization behavior of amorphous active pharmaceutical ingredients (API) exposed to aqueous environments. A set of approximately 50 chemically and physically diverse active pharmaceutical ingredients (APIs) was selected for this study. Two experimental setups were employed to characterize the crystallization behavior of the amorphous API in an aqueous environment. For the first approach, precipitation, as evidenced by the development of turbidity, was induced using the solvent shift method, by mixing concentrated API solutions in DMSO with an aqueous buffer in a capillary. Subsequently, crystallization was monitored in situ over time using synchrotron radiation (simultaneous SAXS/WAXS beamline 12-ID-B at the Advanced Photon Source, Argonne National Laboratories, Argonne, IL). In the second approach, amorphous films were prepared by melt quenching; after adding buffer, crystallization was monitored with time using polarized light microscopy. In general, the crystallization behavior of a given compound was similar irrespective of the experimental method employed. However, the crystallization behavior among different compounds varied significantly, ranging from immediate and complete crystallization to no observable crystallization over biorelevant time scales. Comparison of the observed behavior with previous studies of crystallization tendency in non-aqueous environments revealed that the crystallization tendency of individual APIs was somewhat similar regardless of the crystallization environment. API properties, rather than the method by which amorphous materials are generated, tend to dictate crystallization behavior in aqueous media.

Stability of Atenolol, Clonazepam, Dexamethasone, Diclofenac Sodium, Diltiazem, Enalapril Maleate, Ketoprofen, Lamotrigine, Penicillamine-D, and Thiamine in SyrSpend SF PH4 Oral Suspensions.

PubMed

Polonini, Hudson C; Loures, Sharlene; Lima, Luis Claudio; Ferreira, Anderson O; Brandão, Marcos Antônio F

2016-01-01

The objective of this study was to evaluate the stability of 10 commonly used active pharmaceutical ingredients compounded in oral suspensions using SyrSpend SF PH4 (atenolol 1.0 and 5.0 mg/mL, clonazepam 0.2 mg/mL, dexamethasone 1.0 mg/mL, diclofenac sodium 5.0 mg/mL, diltiazem 12.0 mg/mL, enalapril maleate 1.0 mg/mL, ketoprofen 20.0 mg/mL, lamotrigine 1.0 mg/mL, penicillamine-D 50.0 mg/mL, thiamine 100 mg/m) and stored both at controlled refrigerated (2°C to 8°C) and room temperature (20°C to 25°C). Stability was assessed by means of measuring percent recovery at varying time points throughout a 90-day period. The quantification of the active pharmaceutical ingredients was performed by a stability-indicating, high-performance liquid chromatographic method. The beyond-use date of the products was found to be at least 90 days for all suspensions (except atenolol 1 mg/mL, which was stable up to 60 days), both for controlled refrigerated temperature and room temperature. This confirms that SyrSpend SF PH4 is a stable suspending vehicle for compounding with a broad range of different active pharmaceutical ingredients.

Synthesis and antimycobacterial activity of isoniazid derivatives from renewable fatty acids.

PubMed

Rodrigues, Marieli O; Cantos, Jéssica B; D'Oca, Caroline R Montes; Soares, Karina L; Coelho, Tatiane S; Piovesan, Luciana A; Russowsky, Dennis; da Silva, Pedro A; D'Oca, Marcelo G Montes

2013-11-15

This work describes the synthesis of a series of fatty acid hydrazide derivatives of isoniazid (INH). The compounds were tested against Mycobacterium tuberculosis H37Rv (ATCC 27294) as well as INH-resistant (ATCC 35822 and 1896 HF) and rifampicin-resistant (ATCC 35338) M. tuberculosis strains. The fatty acid derivatives of INH showed high antimycobacterial potency against the studied strains, which is desirable for a pharmaceutical compound, suggesting that the increased lipophilicity of isoniazid plays an important role in its antimycobacterial activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Adsorption characteristics of selected pharmaceuticals and an endocrine disrupting compound-Naproxen, carbamazepine and nonylphenol-on activated carbon.

PubMed

Yu, Zirui; Peldszus, Sigrid; Huck, Peter M

2008-06-01

The adsorption of two representative pharmaceutically active compounds (PhACs) (naproxen and carbamazepine) and one endocrine disrupting compound (nonylphenol) were evaluated on two types of activated carbon. When determining their isotherms at environmentally relevant concentration levels, it was found that at this low concentration range (10-800 ng/L), removals of the target compounds were contrary to expectations based on their hydrophobicity. Nonylphenol (log K(ow) 5.8) was most poorly adsorbed, whereas carbamazepine (log K(ow) 2.45) was most adsorbable. Nonylphenol Freundlich isotherms at this very low concentration range had a much higher 1/n compared to isotherms at much higher concentrations. This indicates that extrapolation from an isotherm obtained at a high concentration range to predict the adsorption of nonylphenol at a concentration well below the range of the original isotherm, leads to a substantial overestimation of its removals. Comparison of isotherms for the target compounds to those for other conventional micropollutants suggested that naproxen and carbamazepine could be effectively removed by applying the same dosage utilized to remove odorous compounds (geosmin and MIB) at very low concentrations. The impact of competitive adsorption by background natural organic matter (NOM) on the adsorption of the target compounds was quantified by using the ideal adsorbed solution theory (IAST) in combination with the equivalent background compound (EBC) approach. The fulfilment of the requirements for applying the simplified IAST-EBC model, which leads to the conclusion that the percentage removal of the target compounds at a given carbon dosage is independent of the initial contaminant concentration, was confirmed for the situation examined in the paper. On this basis it is suggested that the estimated minimum carbon usage rates (CURs) to achieve 90% removal of these emerging contaminants would be valid at concentrations of less than 500 ng/L in natural water.

Compound annotation with real time cellular activity profiles to improve drug discovery.

PubMed

Fang, Ye

2016-01-01

In the past decade, a range of innovative strategies have been developed to improve the productivity of pharmaceutical research and development. In particular, compound annotation, combined with informatics, has provided unprecedented opportunities for drug discovery. In this review, a literature search from 2000 to 2015 was conducted to provide an overview of the compound annotation approaches currently used in drug discovery. Based on this, a framework related to a compound annotation approach using real-time cellular activity profiles for probe, drug, and biology discovery is proposed. Compound annotation with chemical structure, drug-like properties, bioactivities, genome-wide effects, clinical phenotypes, and textural abstracts has received significant attention in early drug discovery. However, these annotations are mostly associated with endpoint results. Advances in assay techniques have made it possible to obtain real-time cellular activity profiles of drug molecules under different phenotypes, so it is possible to generate compound annotation with real-time cellular activity profiles. Combining compound annotation with informatics, such as similarity analysis, presents a good opportunity to improve the rate of discovery of novel drugs and probes, and enhance our understanding of the underlying biology.

Tracking 20 Years of Compound-to-Target Output from Literature and Patents

PubMed Central

Southan, Christopher; Varkonyi, Peter; Boppana, Kiran; Jagarlapudi, Sarma A.R.P.; Muresan, Sorel

2013-01-01

The statistics of drug development output and declining yield of approved medicines has been the subject of many recent reviews. However, assessing research productivity that feeds development is more difficult. Here we utilise an extensive database of structure-activity relationships extracted from papers and patents. We have used this database to analyse published compounds cumulatively linked to nearly 4000 protein target identifiers from multiple species over the last 20 years. The compound output increases up to 2005 followed by a decline that parallels a fall in pharmaceutical patenting. Counts of protein targets have plateaued but not fallen. We extended these results by exploring compounds and targets for one large pharmaceutical company. In addition, we examined collective time course data for six individual protease targets, including average molecular weight of the compounds. We also tracked the PubMed profile of these targets to detect signals related to changes in compound output. Our results show that research compound output had decreased 35% by 2012. The major causative factor is likely to be a contraction in the global research base due to mergers and acquisitions across the pharmaceutical industry. However, this does not rule out an increasing stringency of compound quality filtration and/or patenting cost control. The number of proteins mapped to compounds on a yearly basis shows less decline, indicating the cumulative published target capacity of global research is being sustained in the region of 300 proteins for large companies. The tracking of six individual targets shows uniquely detailed patterns not discernible from cumulative snapshots. These are interpretable in terms of events related to validation and de-risking of targets that produce detectable follow-on surges in patenting. Further analysis of the type we present here can provide unique insights into the process of drug discovery based on the data it actually generates. PMID:24204758

Occurrence and removal of pharmaceuticals and personal care products (PPCPs) in an advanced wastewater reclamation plant.

PubMed

Yang, Xin; Flowers, Riley C; Weinberg, Howard S; Singer, Philip C

2011-10-15

The occurrence of nineteen pharmaceutically active compounds and personal care products was followed monthly for 12 months after various stages of treatment in an advanced wastewater reclamation plant in Gwinnett County, GA, U.S.A. Twenty-four hour composite samples were collected after primary clarification, activated sludge biological treatment, membrane filtration, granular media filtration, granular activated carbon (GAC) adsorption, and ozonation in the wastewater reclamation plant. Compounds were identified and quantified using high performance liquid chromatography/tandem mass spectrometry (LC-MS/MS) and gas chromatography/mass spectrometry (GC-MS) after solid-phase extraction. Standard addition methods were employed to compensate for matrix effects. Sixteen of the targeted compounds were detected in the primary effluent; sulfadimethoxine, doxycycline, and iopromide were not found. Caffeine and acetaminophen were found at the highest concentrations (∼10(5) ng/L), followed by ibuprofen (∼10(4) ng/L), sulfamethoxazole and DEET (∼10(3) ng/L). Most of the other compounds were found at concentrations on the order of hundreds of ng/L. After activated sludge treatment and membrane filtration, the concentrations of caffeine, acetaminophen, ibuprofen, DEET, tetracycline, and 17α-ethynylestradiol (EE2) had decreased by more than 90%. Erythromycin and carbamazepine, which were resistant to biological treatment, were eliminated by 74 and 88%, on average, by GAC. Primidone, DEET, and caffeine were not amenable to adsorption by GAC. Ozonation oxidized most of the remaining compounds by >60%, except for primidone and DEET. Of the initial 16 compounds identified in the primary effluent, only sulfamethoxazole, primidone, caffeine and DEET were frequently detected in the final effluent, but at concentrations on the order of 10-100 ng/L. Removal of the different agents by the various treatment processes was related to the physical-chemical properties of the compounds. Copyright © 2011 Elsevier Ltd. All rights reserved.

Current trends in green liquid chromatography for the analysis of pharmaceutically active compounds in the environmental water compartments.

PubMed

Shaaban, Heba; Górecki, Tadeusz

2015-01-01

Green analytical chemistry is an aspect of green chemistry which introduced in the late nineties. The main objectives of green analytical chemistry are to obtain new analytical technologies or to modify an old method to incorporate procedures that use less hazardous chemicals. There are several approaches to achieve this goal such as using environmentally benign solvents and reagents, reducing the chromatographic separation times and miniaturization of analytical devices. Traditional methods used for the analysis of pharmaceutically active compounds require large volumes of organic solvents and generate large amounts of waste. Most of them are volatile and harmful to the environment. With the awareness about the environment, the development of green technologies has been receiving increasing attention aiming at eliminating or reducing the amount of organic solvents consumed everyday worldwide without loss in chromatographic performance. This review provides the state of the art of green analytical methodologies for environmental analysis of pharmaceutically active compounds in the aquatic environment with special emphasis on strategies for greening liquid chromatography (LC). The current trends of fast LC applied to environmental analysis, including elevated mobile phase temperature, as well as different column technologies such as monolithic columns, fully porous sub-2 μm and superficially porous particles are presented. In addition, green aspects of gas chromatography (GC) and supercritical fluid chromatography (SFC) will be discussed. We pay special attention to new green approaches such as automation, miniaturization, direct analysis and the possibility of locating the chromatograph on-line or at-line as a step forward in reducing the environmental impact of chromatographic analyses. Copyright © 2014 Elsevier B.V. All rights reserved.

Concentrations of hormones, pharmaceuticals and other micropollutants in groundwater affected by septic systems in New England and New York.

PubMed

Phillips, P J; Schubert, C; Argue, D; Fisher, I; Furlong, E T; Foreman, W; Gray, J; Chalmers, A

2015-04-15

Septic-system discharges can be an important source of micropollutants (including pharmaceuticals and endocrine active compounds) to adjacent groundwater and surface water systems. Groundwater samples were collected from well networks tapping glacial till in New England (NE) and sandy surficial aquifer New York (NY) during one sampling round in 2011. The NE network assesses the effect of a single large septic system that receives discharge from an extended health care facility for the elderly. The NY network assesses the effect of many small septic systems used seasonally on a densely populated portion of Fire Island. The data collected from these two networks indicate that hydrogeologic and demographic factors affect micropollutant concentrations in these systems. The highest micropollutant concentrations from the NE network were present in samples collected from below the leach beds and in a well downgradient of the leach beds. Total concentrations for personal care/domestic use compounds, pharmaceutical compounds and plasticizer compounds generally ranged from 1 to over 20 μg/L in the NE network samples. High tris(2-butoxyethyl phosphate) plasticizer concentrations in wells beneath and downgradient of the leach beds (>20 μg/L) may reflect the presence of this compound in cleaning agents at the extended health-care facility. The highest micropollutant concentrations for the NY network were present in the shoreline wells and reflect groundwater that is most affected by septic system discharges. One of the shoreline wells had personal care/domestic use, pharmaceutical, and plasticizer concentrations ranging from 0.4 to 5.7 μg/L. Estradiol equivalency quotient concentrations were also highest in a shoreline well sample (3.1 ng/L). Most micropollutant concentrations increase with increasing specific conductance and total nitrogen concentrations for shoreline well samples. These findings suggest that septic systems serving institutional settings and densely populated areas in coastal settings may be locally important sources of micropollutants to adjacent aquifer and marine systems. Published by Elsevier B.V.

Pharmaceutical removal in tropical subsurface flow constructed wetlands at varying hydraulic loading rates.

PubMed

Zhang, Dong Qing; Gersberg, Richard M; Hua, Tao; Zhu, Junfei; Tuan, Nguyen Anh; Tan, Soon Keat

2012-04-01

Determining the fate of emerging organic contaminants in an aquatic ecosystem is important for developing constructed wetlands (CWs) treatment technology. Experiments were carried out in subsurface flow CWs in Singapore to evaluate the fate and transport of eight pharmaceutical compounds. The CW system included three parallel horizontal subsurface flow CWs and three parallel unplanted beds fed continuously with synthetic wastewater at different hydraulic retention times (HRTs). The findings of the tests at 2-6 d HRTs showed that the pharmaceuticals could be categorized as (i) efficiently removed compounds with removal higher than 85% (ketoprofen and salicylic acid); (ii) moderately removed compounds with removal efficiencies between 50% and 85% (naproxen, ibuprofen and caffeine); and (iii) poorly removed compounds with efficiency rate lower than 50% (carbamazepine, diclofenac, and clofibric acid). Except for carbamazepine and salicylic acid, removal efficiencies of the selected pharmaceuticals showed significant (p<0.05) enhancement in planted beds as compared to the unplanted beds. Removal of caffeine, ketoprofen and clofibric acid were found to follow first order decay kinetics with decay constants higher in the planted beds than the unplanted beds. Correlations between pharmaceutical removal efficiencies and log K(ow) were not significant (p>0.05), implying that their removal is not well related to the compound's hydrophobicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Why Become Pharmacy Compounding Accreditation Board Accredited?

PubMed

Dillon, L Rad

2016-01-01

The Pharmacy Compounding Accreditation Board's goal is to assist pharmacies to obtain formal recognition of their status as a high-quality and fully compliant provider of pharmaceuticals and patient services. This article provides a brief outline of the application process, the survey preparation, points of information about the actual survey, and suggestions on how to remain in compliance with Pharmacy Compounding Accreditation Board's standards. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Neotropics and natural ingredients for pharmaceuticals: why isn't South American biodiversity on the crest of the wave?

PubMed

Desmarchelier, Cristian

2010-06-01

Despite the advent of biotechnology and modern methods of combinatorial chemistry and rational drug design, nature still plays a surprisingly important role as a source of new pharmaceutical compounds. These are marketed either as herbal drugs or as single active ingredients. South American tropical ecosystems (or the Neotropics) encompass one-third of the botanical biodiversity of the planet. For centuries, indigenous peoples have been using plants for healing purposes, and scientists are making considerable efforts in order to validate these uses from a pharmacological/phytochemical point of view. However, and despite the unique plant diversity in the region, very few natural pharmaceutical ingredients from this part of the world have reached the markets in industrialized countries. The present review addresses the importance of single active ingredients and herbal drugs from South American flora as natural ingredients for pharmaceuticals; it highlights the most relevant cases in terms of species of interest; and discusses the key entry barriers for these products in industrialized countries. It explores the reasons why, in spite of the region's competitive advantages, South American biodiversity has been a poor source of natural ingredients for the pharmaceutical industry. (c) 2010 John Wiley & Sons, Ltd.

Structure-Based Design, Synthesis, Biological Evaluation, and Molecular Docking of Novel PDE10 Inhibitors with Antioxidant Activities

NASA Astrophysics Data System (ADS)

Li, Jinxuan; Chen, Jing-Yi; Deng, Ya-Lin; Zhou, Qian; Wu, Yinuo; Wu, Deyan; Luo, Hai-Bin

2018-05-01

Phosphodiesterase 10 is a promising target for the treatment of a series of central nervous system (CNS) diseases. Imbalance between oxidative stress and antioxidant defense systems as a universal condition in neurodegenerative disorders is widely studied as a potential therapy for CNS diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). To discover multifunctional pharmaceuticals as a treatment for neurodegenerative diseases, a series of quinazoline-based derivatives with PDE10 inhibitory activities and antioxidant activities were designed and synthesized. Nine out of thirteen designed compounds showed good PDE10 inhibition at the concentration of 1.0 μM. Among these compounds, eight exhibited moderate to excellent antioxidant activity with ORAC (oxygen radical absorbance capacity) value above 1.0. Molecular docking was performed for better understanding of the binding patterns of these compounds with PDE10. Compound 11e, which showed remarkable inhibitory activity against PDE10 and antioxidant activity may serve as a lead for the further modification.

Marine Pharmacology in 2012-2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

PubMed

Mayer, Alejandro M S; Rodríguez, Abimael D; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

2017-08-29

The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998-2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products. In addition, 75 marine compounds were reported to have antidiabetic and anti-inflammatory activities and affect the immune and nervous system. Finally, 69 marine compounds were shown to display miscellaneous mechanisms of action which could contribute to novel pharmacological classes. Thus, in 2012-2013, the preclinical marine natural product pharmacology pipeline provided novel pharmacology and lead compounds to the clinical marine pharmaceutical pipeline, and contributed significantly to potentially novel therapeutic approaches to several global disease categories.

Anti-cancer agents based on 6-trifluoromethoxybenzimidazole derivatives and method of making

DOEpatents

Gakh, Andrei A.; Vovk, Mykhaylo V.; Mel'nychenko, Nina V.; Sukach, Volodymyr A.

2012-08-14

The present disclosure relates to novel compounds having the structural Formulas (1a,1b), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof as chemotherapy agents for treating of cancer, particularly androgen-independent prostate cancer. The disclosure also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

Anti-cancer agents based on 6-trifluoromethoxybenzimidazole derivatives and method of making

DOEpatents

Gakh, Andrei A; Vovk, Mykhaylo V; Mel& #x27; nychenko, Nina V; Sukach, Volodymyr A

2012-10-23

The present disclosure relates to novel compounds having the structural Formulas (1a,1b), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof as chemotherapy agents for treating of cancer, particularly androgen-independent prostate cancer. The disclosure also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

Sorption and degradation of wastewater-associated non-steroidal anti-inflammatory drugs and antibiotics in soils.

PubMed

Lin, Kunde; Gan, Jay

2011-04-01

Presence of pharmaceuticals at trace levels in recycled water is an emerging issue impacting the beneficial reuse of treated wastewater, including practices such as irrigation and groundwater recharge in arid and semi-arid regions. To assess the environmental risks of irrigation with recycled water containing such micropollutants, in this study we evaluated sorption and degradation of five pharmaceuticals that are antibiotic and anti-inflammatory drugs in two soils collected from arid regions. Naproxen and trimethoprim showed moderate to strong sorption, while the sorption of diclofenac, ibuprofen and sulfamethoxazole was negligible in both soils. Under aerobic conditions, the studied compounds were susceptible to microbial degradation with half-lives varying from 4.8 to 69.3d. Apart from sulfamethoxazole, the other compounds were relatively persistent under anaerobic conditions as indicated by a negligible loss over 84d of incubation or half-lives >50d. The degradation of the selected pharmaceuticals was influenced by microbial activities, oxygen status in the soil, soil type and compound characteristics. The poor sorption and relative persistence of diclofenac and ibuprofen under anaerobic conditions suggest that the two chemicals may pose a high leaching risk when using recycled for irrigation or groundwater replenishment. Copyright © 2010 Elsevier Ltd. All rights reserved.

Occurrence of cardiovascular drugs in the sewage-impacted Vistula River and in tap water in the Warsaw region (Poland).

PubMed

Giebułtowicz, Joanna; Stankiewicz, Albert; Wroczyński, Piotr; Nałęcz-Jawecki, Grzegorz

2016-12-01

In recent years, cardiovascular diseases were the second most common cause of death worldwide. Therefore, the consumption of drugs used to treat cardiovascular diseases is high. So far, there were no such comprehensive reports regarding the presence of cardiovascular drugs in surface and tap waters, particularly in Central and Eastern Europe. The aim of our study was to determine the presence of 30 pharmaceutically active compounds and some of their metabolites, at specific points of the Vistula River and in tap water samples in the Warsaw region. The analysis was performed using the liquid chromatography-electrospray ionization-tandem mass spectrometry method, coupled to solid-phase extraction. To the best of the authors' knowledge, this is the first time where the presence of ciprofibrate in the environment was investigated. Cardiovascular drugs found at the highest concentrations (reaching 1 μg/L or higher) in surface water were beta-blockers, sartans and diuretics. In tap water samples, trace amounts of pharmaceuticals were detected, for almost all target compounds. This highlights their inadequate elimination by the treatment facility used in the Warsaw region. The presence of cardiovascular compounds in the aquatic environment could have a long-term effect even at a low exposure level, since synergy effects amongst pharmaceuticals may occur.

Fate and Uptake of Pharmaceuticals in Soil–Earthworm Systems

PubMed Central

2014-01-01

Pharmaceuticals present a potential threat to soil organisms, yet our understanding of their fate and uptake in soil systems is limited. This study therefore investigated the fate and uptake of 14C-labeled carbamazepine, diclofenac, fluoxetine, and orlistat in soil–earthworm systems. Sorption coefficients increased in the order of carbamazepine < diclofenac < fluoxetine < orlistat. Dissipation of 14C varied by compound, and for orlistat, there was evidence of formation of nonextractable residues. Uptake of 14C was seen for all compounds. Depuration studies showed complete elimination of 14C for carbamazepine and fluoxetine treatments and partial elimination for orlistat and diclofenac, with greater than 30% of the 14C remaining in the tissue at the end of the experiment. Pore-water-based bioconcentration factors (BCFs), based on uptake and elimination of 14C, increased in the order carbamazepine < diclofenac < fluoxetine and orlistat. Liquid chromatography–tandem mass spectrometry and liquid chromatography–Fourier transform mass spectrometry indicated that the observed uptake in the fluoxetine and carbamazepine treatments was due to the parent compounds but that diclofenac was degraded in the test system so uptake was due to unidentifiable transformation products. Comparison of our data with outputs of quantitative structure−activity relationships for estimating BCFs in worms showed that these models tend to overestimate pharmaceutical BCFs so new models are needed. PMID:24762061

Occurrence of veterinary pharmaceuticals in the aquatic environment in Flanders

NASA Astrophysics Data System (ADS)

Servaes, K.; Vanermen, G.; Seuntjens, P.

2009-04-01

There is a growing interest in the occurrence of pharmaceuticals in the aquatic environment. Pharmaceuticals are classified as so-called ‘emerging pollutants'. ‘Emerging pollutants' are not necessarily new chemical compounds. Often these compounds are already present in the environment for a long time. But, their occurrence and especially their impact on the environment has only recently become clear. Consequently, data on their occurrence are rather scarce. In this study, we focus on the occurrence of veterinary pharmaceuticals in surface water in Flanders. We have only considered active substances administered to cattle, pigs and poultry. Based on the literature and information concerning the use in Belgium, a selection of 25 veterinary pharmaceuticals has been made. This selection consists of the most important antibiotics and antiparasitic substances applied in veterinary medicine in Belgium. We develop an analytical methodology based on UPLC-MS/MS for the detection of these veterinary pharmaceuticals in surface water. Therefore, the mass characteristics as well as the optimum LC conditions will be determined. To obtain limits of detection as low as possible, the samples are concentrated prior to analysis using solid phase extraction (SPE). Different SPE cartridges will be tested during the method development. At first, this SPE sample pre-treatment is performed off-line. In a next step, online SPE is optimized for this purpose. The analytical procedure will be subject to an in-house validation study, thereby determining recovery, repeatability (% RSD), limits of detection and limits of quantification. Finally, the developed methodology will be applied for monitoring the occurrence of veterinary pharmaceuticals in surface water and groundwater in Flanders. These water samples will be taken in areas characterized by intensive cattle breeding. Moreover, the samples will be collected during springtime. In this season, farmers apply manure, stored during winter, onto the fields.

Synthesis of 2 carbon-14 analogue of thioflavanones.

PubMed

Basooti, Mohammad; Saadatjoo, Naghi; Nemati, Firozeh; Shirvani, Gholamhossein; Faghih, Mohammad Amin Ahmadi; Javaheri, Mohsen

2017-09-01

Thioflavanones are prevalent heterocyclic structural units in pharmaceutical and biologically active compound (Scheme ). In this paper, the synthesis of 2-phenylthiochroman-4-ones and 2-phenyl-4H-1-benzothiopyran-4-one labeled with carboxyl-14 is demonstrated. Copyright © 2017 John Wiley & Sons, Ltd.

A QSAR-like analysis of the adsorption of endocrine disrupting compounds, pharmaceuticals, and personal care products on modified activated carbons.

PubMed

Redding, Adam M; Cannon, Fred S; Snyder, Shane A; Vanderford, Brett J

2009-08-01

Rapid small-scale column tests (RSSCTs) examined the removal of 29 endocrine disrupting compounds (EDCs) and pharmaceutical/personal care products (PPCPs). The RSSCTs employed three lignite variants: HYDRODARCO 4000 (HD4000), steam-modified HD4000, and methane/steam-modified HD4000. RSSCTs used native Lake Mead, NV water spiked with 100-200 ppt each of 29 EDCs/PPCPs. For the steam and methane/steam variants, breakthrough occurred at 14,000-92,000 bed volumes (BV); and this was 3-4 times more bed volumes than for HD4000. Most EDC/PPCP bed life data were describable by a normalized quantitative structure-activity relationship (i.e. QSAR-like model) of the form: where TPV is the pore volume, rho(mc) is the apparent density, CV is the molecular volume, C(o) is the concentration, (8)chi(p) depicts the molecule's compactness, and FOSA is the molecule's hydrophobic surface area.

Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds

PubMed Central

Delfosse, Vanessa; Dendele, Béatrice; Huet, Tiphaine; Grimaldi, Marina; Boulahtouf, Abdelhay; Gerbal-Chaloin, Sabine; Beucher, Bertrand; Roecklin, Dominique; Muller, Christina; Rahmani, Roger; Cavaillès, Vincent; Daujat-Chavanieu, Martine; Vivat, Valérie; Pascussi, Jean-Marc; Balaguer, Patrick; Bourguet, William

2015-01-01

Humans are chronically exposed to multiple exogenous substances, including environmental pollutants, drugs and dietary components. Many of these compounds are suspected to impact human health, and their combination in complex mixtures could exacerbate their harmful effects. Here we demonstrate that a pharmaceutical oestrogen and a persistent organochlorine pesticide, both exhibiting low efficacy when studied separately, cooperatively bind to the pregnane X receptor, leading to synergistic activation. Biophysical analysis shows that each ligand enhances the binding affinity of the other, so the binary mixture induces a substantial biological response at doses at which each chemical individually is inactive. High-resolution crystal structures reveal the structural basis for the observed cooperativity. Our results suggest that the formation of ‘supramolecular ligands' within the ligand-binding pocket of nuclear receptors contributes to the synergistic toxic effect of chemical mixtures, which may have broad implications for the fields of endocrine disruption, toxicology and chemical risk assessment. PMID:26333997

Ontology-based content analysis of US patent applications from 2001-2010.

PubMed

Weber, Lutz; Böhme, Timo; Irmer, Matthias

2013-01-01

Ontology-based semantic text analysis methods allow to automatically extract knowledge relationships and data from text documents. In this review, we have applied these technologies for the systematic analysis of pharmaceutical patents. Hierarchical concepts from the knowledge domains of chemical compounds, diseases and proteins were used to annotate full-text US patent applications that deal with pharmacological activities of chemical compounds and filed in the years 2001-2010. Compounds claimed in these applications have been classified into their respective compound classes to review the distribution of scaffold types or general compound classes such as natural products in a time-dependent manner. Similarly, the target proteins and claimed utility of the compounds have been classified and the most relevant were extracted. The method presented allows the discovery of the main areas of innovation as well as emerging fields of patenting activities - providing a broad statistical basis for competitor analysis and decision-making efforts.

Combined effects of pharmaceuticals, personal care products, biocides and organic contaminants on the growth of Skeletonema pseudocostatum.

PubMed

Petersen, Karina; Heiaas, Harald Hasle; Tollefsen, Knut Erik

2014-05-01

Organisms in the environment are exposed to a number of pollutants from different compound groups. In addition to the classic pollutants like the polychlorinated biphenyls, polyaromatic hydrocarbons (PAHs), alkylphenols, biocides, etc. other compound groups of concern are constantly emerging. Pharmaceuticals and personal care products (PPCPs) can be expected to co-occur with other organic contaminants like biocides, PAHs and alkylphenols in areas affected by wastewater, industrial effluents and intensive recreational activity. In this study, representatives from these four different compound groups were tested individually and in mixtures in a growth inhibition assay with the marine algae Skeletonema pseudocostatum (formerly Skeletonema costatum) to determine whether the combined effects could be predicted by models for additive effects; the concentration addition (CA) and independent action (IA) prediction model. The eleven tested compounds reduced the growth of S. pseudocostatum in the microplate test in a concentration-dependent manner. The order of toxicity of these chemicals were irgarol>fluoxetine>diuron>benzo(a)pyrene>thioguanine>triclosan>propranolol>benzophenone 3>cetrimonium bromide>4-tert-octylphenol>endosulfan. Several binary mixtures and a mixture of eight compounds from the four different compound groups were tested. All tested mixtures were additive as model deviation ratios, the deviation between experimental and predicted effect concentrations, were within a factor of 2 from one or both prediction models (e.g. CA and IA). Interestingly, a concentration dependent shift from IA to CA, potentially due to activation of similar toxicity pathways at higher concentrations, was observed for the mixture of eight compounds. The combined effects of the multi-compound mixture were clearly additive and it should therefore be expected that PPCPs, biocides, PAHs and alkylphenols will collectively contribute to the risk in areas contaminated by such complex mixtures. Copyright © 2014 Elsevier B.V. All rights reserved.

Polymorphs and Prodrugs and Salts (Oh My!): An Empirical Analysis of “Secondary” Pharmaceutical Patents

PubMed Central

2012-01-01

Background While there has been much discussion by policymakers and stakeholders about the effects of “secondary patents” on the pharmaceutical industry, there is no empirical evidence on their prevalence or determinants. Characterizing the landscape of secondary patents is important in light of recent court decisions in the U.S. that may make them more difficult to obtain, and for developing countries considering restrictions on secondary patents. Methodology/Principal Findings We read the claims of the 1304 Orange Book listed patents on all new molecular entities approved in the U.S. between 1988 and 2005, and coded the patents as including chemical compound claims (claims covering the active molecule itself) and/or one of several types of secondary claims. We distinguish between patents with any secondary claims, and those with only secondary claims and no chemical compound claims (“independent” secondary patents). We find that secondary claims are common in the pharmaceutical industry. We also show that independent secondary patents tend to be filed and issued later than chemical compound patents, and are also more likely to be filed after the drug is approved. When present, independent formulation patents add an average of 6.5 years of patent life (95% C.I.: 5.9 to 7.3 years), independent method of use patents add 7.4 years (95% C.I.: 6.4 to 8.4 years), and independent patents on polymorphs, isomers, prodrug, ester, and/or salt claims add 6.3 years (95% C.I.: 5.3 to 7.3 years). We also provide evidence that late-filed independent secondary patents are more common for higher sales drugs. Conclusions/Significance Policies and court decisions affecting secondary patenting are likely to have a significant impact on the pharmaceutical industry. Secondary patents provide substantial additional patent life in the pharmaceutical industry, at least nominally. Evidence that they are also more common for best-selling drugs is consistent with accounts of active “life cycle management” or “evergreening” of patent portfolios in the industry. PMID:23227141

Tracking persistent pharmaceutical residues from municipal sewage to drinking water

NASA Astrophysics Data System (ADS)

Heberer, Thomas

2002-09-01

In urban areas such as Berlin (Germany) with high municipal sewage water discharges and low surface water flows there is a potential risk of drinking water contamination by polar organic compounds when groundwater recharge is used in drinking water production. Thus, some pharmaceutically active compounds (PhACs) are not eliminated completely in the municipal sewage treatment plants (STPs) and they are discharged as contaminants into the receiving waters. In terms of several monitoring studies carried out in Berlin between 1996 and 2000, PhACs such as clofibric acid, diclofenac, ibuprofen, propyphenazone, primidone and carbamazepine were detected at individual concentrations up to the μg/l-level in influent and effluent samples from STPs and in all surface water samples collected downstream from the STPs. Under recharge conditions, several compounds were also found at individual concentrations up to 7.3 μg/l in samples collected from groundwater aquifers near to contaminated water courses. A few of the PhACs were also identified at the ng/l-level in Berlin tap water samples.

G protein-coupled receptor internalization assays in the high-content screening format.

PubMed

Haasen, Dorothea; Schnapp, Andreas; Valler, Martin J; Heilker, Ralf

2006-01-01

High-content screening (HCS), a combination of fluorescence microscopic imaging and automated image analysis, has become a frequently applied tool to study test compound effects in cellular disease-modeling systems. This chapter describes the measurement of G protein-coupled receptor (GPCR) internalization in the HCS format using a high-throughput, confocal cellular imaging device. GPCRs are the most successful group of therapeutic targets on the pharmaceutical market. Accordingly, the search for compounds that interfere with GPCR function in a specific and selective way is a major focus of the pharmaceutical industry today. This chapter describes methods for the ligand-induced internalization of GPCRs labeled previously with either a fluorophore-conjugated ligand or an antibody directed against an N-terminal tag of the GPCR. Both labeling techniques produce robust assay formats. Complementary to other functional GPCR drug discovery assays, internalization assays enable a pharmacological analysis of test compounds. We conclude that GPCR internalization assays represent a valuable medium/high-throughput screening format to determine the cellular activity of GPCR ligands.

Chlorodifluoromethane-triggered formation of difluoromethylated arenes catalysed by palladium

NASA Astrophysics Data System (ADS)

Feng, Zhang; Min, Qiao-Qiao; Fu, Xia-Ping; An, Lun; Zhang, Xingang

2017-09-01

Difluoromethylated aromatic compounds are of increasing importance in pharmaceuticals, agrochemicals and materials. Chlorodifluoromethane (ClCF2H), an inexpensive, abundant and widely used industrial raw material, represents the ideal and most straightforward difluoromethylating reagent, but introduction of the difluoromethyl group (CF2H) from ClCF2H into aromatics has not been reported. Here, we describe a direct palladium-catalysed difluoromethylation method for coupling ClCF2H with arylboronic acids and esters to generate difluoromethylated arenes with high efficiency. The reaction exhibits a remarkably broad substrate scope, including heteroarylboronic acids, and was used for difluoromethylation of a range of pharmaceuticals and biologically active compounds. Preliminary mechanistic studies revealed that a palladium difluorocarbene intermediate is involved in the reaction. Although numerous metal-difluorocarbene complexes have been prepared, the catalytic synthesis of difluoromethylated or difluoromethylenated compounds involving metal-difluorocarbene complexes has not received much attention. This new reaction therefore also opens the door to understand metal-difluorocarbene complex catalysed reactions.

Identifying new persistent and bioaccumulative organics among chemicals in commerce II: pharmaceuticals.

PubMed

Howard, Philip H; Muir, Derek C G

2011-08-15

The goal of this study was to identify commercial pharmaceuticals that might be persistent and bioaccumulative (P&B) and that were not being considered in current wastewater and aquatic environmental measurement programs. We developed a database of 3193 pharmaceuticals from two U.S. Food and Drug Administration (FDA) databases and some lists of top ranked or selling drugs. Of the 3193 pharmaceuticals, 275 pharmaceuticals have been found in the environment and 399 pharmaceuticals were, based upon production volumes, designated as high production volume (HPV) pharmaceuticals. All pharmaceuticals that had reported chemical structures were evaluated for potential bioaccumulation (B) or persistence (P) using quantitative structure property relationships (QSPR) or scientific judgment. Of the 275 drugs detected in the environment, 92 were rated as potentially bioaccumulative, 121 were rated as potentially persistent, and 99 were HPV pharmaceuticals. After removing the 275 pharmaceuticals previously detected in the environment, 58 HPV compounds were identified that were both P&B and 48 were identified as P only. Of the non-HPV compounds, 364 pharmaceuticals were identified that were P&B. This study has yielded some interesting and probable P&B pharmaceuticals that should be considered for further study.

Thermodynamic behavior of glassy state of structurally related compounds.

PubMed

Kaushal, Aditya Mohan; Bansal, Arvind Kumar

2008-08-01

Thermodynamic properties of amorphous pharmaceutical forms are responsible for enhanced solubility as well as poor physical stability. The present study was designed to investigate the differences in thermodynamic parameters arising out of disparate molecular structures and associations for four structurally related pharmaceutical compounds--celecoxib, valdecoxib, rofecoxib, and etoricoxib. Conventional and modulated temperature differential scanning calorimetry were employed to study glass forming ability and thermodynamic behavior of the glassy state of model compounds. Glass transition temperature of four glassy compounds was in a close range of 327.6-331.8 K, however, other thermodynamic parameters varied considerably. Kauzmann temperature, strength parameter and fragility parameter showed rofecoxib glass to be most fragile of the four compounds. Glass forming ability of the compounds fared similar in the critical cooling rate experiments, suggesting that different factors were determining the glass forming ability and subsequent behavior of the compounds in glassy state. A comprehensive understanding of such thermodynamic facets of amorphous form would help in rationalizing the approaches towards development of stable glassy pharmaceuticals.

Informing the Human Plasma Protein Binding of ...

EPA Pesticide Factsheets

The free fraction of a xenobiotic in plasma (Fub) is an important determinant of chemical adsorption, distribution, metabolism, elimination, and toxicity, yet experimental plasma protein binding data is scarce for environmentally relevant chemicals. The presented work explores the merit of utilizing available pharmaceutical data to predict Fub for environmentally relevant chemicals via machine learning techniques. Quantitative structure-activity relationship (QSAR) models were constructed with k nearest neighbors (kNN), support vector machines (SVM), and random forest (RF) machine learning algorithms from a training set of 1045 pharmaceuticals. The models were then evaluated with independent test sets of pharmaceuticals (200 compounds) and environmentally relevant ToxCast chemicals (406 total, in two groups of 238 and 168 compounds). The selection of a minimal feature set of 10-15 2D molecular descriptors allowed for both informative feature interpretation and practical applicability domain assessment via a bounded box of descriptor ranges and principal component analysis. The diverse pharmaceutical and environmental chemical sets exhibit similarities in terms of chemical space (99-82% overlap), as well as comparable bias and variance in constructed learning curves. All the models exhibit significant predictability with mean absolute errors (MAE) in the range of 0.10-0.18 Fub. The models performed best for highly bound chemicals (MAE 0.07-0.12), neutrals (MAE 0

Development and validation of an LC-UV method for the quantification and purity determination of the novel anticancer agent C1311 and its pharmaceutical dosage form.

PubMed

den Brok, Monique W J; Nuijen, Bastiaan; Hillebrand, Michel J X; Grieshaber, Charles K; Harvey, Michael D; Beijnen, Jos H

2005-09-01

C1311 (5-[[2-(diethylamino)ethyl]amino]-8-hydroxyimidazo [4,5,1-de]-acridin-6-one-dihydrochloride trihydrate) is the lead compound from the group of imidazoacridinones, a novel group of rationally designed anticancer agents. The pharmaceutical development of C1311 necessitated the availability of an assay for the quantification and purity determination of C1311 active pharmaceutical ingredient (API) and its pharmaceutical dosage form. A reversed-phase liquid chromatographic method (RP-LC) with ultraviolet (UV) detection was developed, consisting of separation on a C18 column with phosphate buffer (60 mM; pH 3 with 1 M citric acid)-acetonitrile-triethylamine (83:17:0.05, v/v/v) as the mobile phase and UV-detection at 280 nm. The method was found to be linear over a concentration range of 2.50-100 microg/mL, precise and accurate. Accelerated stress testing showed degradation products, which were well separated from the parent compound, confirming its stability-indicating capacity. Moreover, the use of LC-MS and on-line photo diode array detection enabled us to propose structures for four degradation products. Two of these products were also found as impurities in the API and more abundantly in an impure lot of API.

Raman Spectroscopy of Cocrystals

NASA Astrophysics Data System (ADS)

Rooney, Frank; Reardon, Paul; Ochoa, Romulo; Abourahma, Heba; Marti, Marcus; Dimeo, Rachel

2010-02-01

Cocrystals are a class of compounds that consist of two or more molecules that are held together by hydrogen bonding. Pharmaceutical cocrystals are those that contain an active pharmaceutical ingredient (API) as one of the components. Pharmaceutical cocrystals are of particular interest and have gained a lot of attention in recent years because they offer the ability to modify the physical properties of the API, like solubility and bioavailability, without altering the chemical structure of the API. The APIs that we targeted for our studies are theophylline (Tp) and indomethacin (Ind). These compounds have been mixed with complementary coformers (cocrystal former) that include acetamide (AcONH2), melamine (MLM), nicotinic acid (Nic-COOH), 4-cyanopyridine (4-CNPy) and 4-aminopyridine (4-NH2Py). Raman spectroscopy has been used to characterize these cocrystals. Spectra of the cocrystals were compared to those of the coformers to analyze for peak shifts, specifically those corresponding to hydrogen bonding. A 0.5 m CCD Spex spectrometer was used, in a micro-Raman setup, for spectral analysis. An Argon ion Coherent laser at 514.5 nm was used as the excitation source. )

A Simple and Direct LC-MS Method for Determination of Genotoxic Impurity Hydroxylamine in Pharmaceutical compounds.

PubMed

Kumar, Thangarathinam; Ramya, Mohandass; Srinivasan, Viswanathan; Xavier, N

2017-08-01

Hydroxylamine is a known genotoxic impurity compound that needs to be controlled down to ppm level in pharmaceutical processes. It is difficult to detect using conventional analytical techniques due to its physio-chemical properties like lack of chromophore, low molecular weight, absence of carbon atom and high polarity. In addition to that, analysis of the pharmaceutical samples encounters considerable obstruction from matrix components that greatly overshadow the response of hydroxylamine. This study describes a simple, sensitive and direct Liquid Chromatographic-Mass Spectrometric method (LC-MS) for detection of hydroxylamine in pharmaceutical compounds. The LC-MS method was detected up to 0.008 ppm of hydroxylamine with S/N > 3.0 and quantified up to 0.025 ppm of hydroxylamine with S/N ratio >10.0. This validated method can be applied as a generic method to detect the hydroxylamine for pharmaceutical process control and drug substance release. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Antioxidant and anti-inflammatory activities of hydroxybenzyl alcohol releasing biodegradable polyoxalate nanoparticles.

PubMed

Park, Hyunjin; Kim, Soojin; Kim, Sujin; Song, Yiseul; Seung, Kyungryul; Hong, Donghyun; Khang, Gilson; Lee, Dongwon

2010-08-09

p-Hydroxybenzyl alcohol (HBA) is one of phenolic compounds in herbal agents and plays a pivotal role in protection against oxidative damage-related diseases due to anti-inflammatory effects. We have developed a new biodegradable and anti-inflammatory peroxalate copolymer in which HBA is chemically incorporated into its backbone. The HBA-incorporated copolyoxalate (HPOX) was synthesized from a condensation reaction of oxalyl chloride, 1,4-cyclohexamethanol and HBA and was capable of releasing pharmaceutically active HBA during hydrolytic degradation. HPOX could be dispersed into a single emulsion for the formulation of nanoparticles which had a mean size approximately 500 nm in diameter. The nanoparticles released HBA which was able to inhibit the production of nitric oxide (NO) by suppressing the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells. HPOX nanoparticles also reduced the production of tumor necrosis factor-alpha (TNF-alpha). The remarkable features of HPOX are that the polymer degrades completely into small molecules and one of degradation products is a pharmaceutically active compound. We anticipate that HPOX is highly potent and versatile for the treatment of inflammatory diseases.

Quantitative analysis of active compounds in pharmaceutical preparations by use of attenuated total-reflection Fourier transform mid-infrared spectrophotometry and the internal standard method.

PubMed

Sastre Toraño, J; van Hattum, S H

2001-10-01

A new method is presented for the quantitative analysis of compounds in pharmaceutical preparations Fourier transform (FT) mid-infrared (MIR) spectroscopy with an attenuated total reflection (ATR) module. Reduction of the quantity of overlapping absorption bands, by interaction of the compound of interest with an appropriate solvent, and the employment of an internal standard (IS), makes MIR suitable for quantitative analysis. Vigabatrin, as active compound in vigabatrin 100-mg capsules, was used as a model compound for the development of the method. Vigabatrin was extracted from the capsule content with water after addition of a sodium thiosulfate IS solution. The extract was concentrated by volume reduction and applied to the FTMIR-ATR module. Concentrations of unknown samples were calculated from the ratio of the vigabatrin band area (1321-1610 cm(-1)) and the IS band area (883-1215 cm(-1)) using a calibration standard. The ratio of the area of the vigabatrin peak to that of the IS was linear with the concentration in the range of interest (90-110 mg, in twofold; n=2). The accuracy of the method in this range was 99.7-100.5% (n=5) with a variability of 0.4-1.3% (n=5). The comparison of the presented method with an HPLC assay showed similar results; the analysis of five vigabatrin 100-mg capsules resulted in a mean concentration of 102 mg with a variation of 2% with both methods.

H1-A, a compound isolated from Fusarium oxysporum inhibits hepatitis C virus (HCV) NS3 serine protease.

PubMed

Yang, Li-Yuan; Lin, Jun; Zhou, Bin; Liu, Yan-Gang; Zhu, Bao-Quan

2016-04-01

The present study was aimed to isolate the active compounds from the fermentation products of Fusarium oxysporum, which had hepatitis C virus (HCV) NS3 protease inhibitory activity. A bioactive compound was isolated by reverse-phase silica-gel column chromatography, silica-gel column chromatography, semi-preparative reverse-phase High Performance Liquid Chromatography (HPLC), and then its molecular structure was elucidated based on the spectrosopic analysis. As a result, the compound (H1-A, 1) Ergosta-5, 8 (14), 22-trien-7-one, 3-hydroxy-,(3β, 22E) was isolated and identified. To the best of our knowledge, this was the first report on the isolation of H1-A from microorganisms with the inhibitory activity of NS3 protease. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Short-term tests with a pilot sewage plant and biofilm reactors for the biological degradation of the pharmaceutical compounds clofibric acid, ibuprofen, and diclofenac.

PubMed

Zwiener, C; Frimmel, F H

2003-06-20

The biodegradation of three active compounds of pharmaceuticals clofibric acid, ibuprofen, and diclofenac was investigated in short-term tests with a pilot sewage plant (PSP) and biofilm reactors (BFR, oxic and anoxic) as model systems for municipal sewage treatment. The PSP was characterized with respect to mixing behavior, the BFR with respect to biofilm content and sorption of the pharmaceutical compounds. The short-term experiments were carried out for 55 h in the PSP and for 48 h in the BFR. The concentration of the pharmaceuticals was in the microgram per liter range in presence of readily biodegradable substances in the milligram per liter range. Therefore, a too short time period and too low concentration to promote adaption of the microorganisms were applied. Under the operating conditions applied the biodegradation of the lipid lowering agent clofibric acid and the analgesic agents ibuprofen and diclofenac in the oxic BFR resembled that in the PSP. Clofibric acid and diclofenac were not eliminated and reached a level of approximately 95% of their initial concentration, whereas the concentration of ibuprofen was decreased to approximately 40% in the PSP and to approximately 35% in the oxic BFR. Both systems showed, therefore, an inherent ability for ibuprofen biodegradation. Elimination in the anoxic BFR resulted in a decrease of the concentration of all three substances to values between 60 and 80% of their initial concentration. In contrast to the PSP acetone revealed as inhibitor in the BFR. In both systems acetone was not degraded in the short-term tests.

Multifunctional ligand for use as a diagnostic or therapeutic pharmaceutical

DOEpatents

Katti, Kattesh V.; Volkert, Wynn A.; Ketring, Alan R.; Singh, Prahlad R.

1996-01-01

A compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical comprises either a phosphorous or germanium core and at least two hydrazine groups forming a ligand for bonding to a metal extending from the phosphorous or germanium core.

Temporal trends of select pharmaceutical compounds entering an estuary from a small, urban river

EPA Science Inventory

The fate and effects of pharmaceutical compounds have been widely studied in freshwater systems; however, less is known about their behavior in marine ecosystems. In many coastal watersheds, there are river systems that are receiving waters for domestic wastewater treatment effl...

Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds

PubMed Central

Loh, Yong Yao; Nagao, Kazunori; Hoover, Andrew J.; Hesk, David; Rivera, Nelo R.; Colletti, Steven L.; Davies, Ian W.; MacMillan, David W. C.

2018-01-01

Deuterium- and tritium-labeled pharmaceutical compounds are pivotal diagnostic tools in drug discovery research, providing vital information about the biological fate of drugs and drug metabolites. Herein we demonstrate that a photoredox-mediated hydrogen atom transfer protocol can efficiently and selectively install deuterium (D) and tritium (T) at α-amino sp3 carbon-hydrogen bonds in a single step, using isotopically labeled water (D2O or T2O) as the source of hydrogen isotope. In this context, we also report a convenient synthesis of T2O from T2, providing access to high-specific-activity T2O. This protocol has been successfully applied to the high incorporation of deuterium and tritium in 18 drug molecules, which meet the requirements for use in ligand-binding assays and absorption, distribution, metabolism, and excretion studies. PMID:29123019

Passive sampling - a tool for targeted screening of emerging pollutants in rivers

NASA Astrophysics Data System (ADS)

Kodes, Vit; Grabic, Roman

2016-04-01

A screening of more than 300 pollutants such as pharmaceuticals (analgesics, psycholeptics, antidepressants, antibiotics, beta blockers), PCPs (UV blockers, musk's, repellents), illicit drugs, pesticides, perfluorinated compounds and their metabolites at 22 monitoring sites throughout the Czech Republic was conducted in 2013. POCIS samplers were used in this study. Two types of passive samplers (pesticide and pharmaceutical POCIS) were deployed for 14 days in May and in October, 88 samples were collected in total. In total 265 and 310 target compounds were analyzed in pharmaceutical and pesticide samplers respectively. The chemicals of interest were extracted from the passive samplers according to standardized procedures. LC -MS/MS and LC-MS/HRMS methods were applied for analyses of extracts. 150 of 310 (48%) and 127 of 265 (48%) analyzed substances had been found in pesticide and pharmaceutical samplers respectively. 27 substances (pharmaceuticals, PCPs, pesticides, caffeine, nicotine metabolite cotinine) occurred at all sampled sites, additional 39 substances (pharmaceuticals, PCPs, pesticides) occurred at more than 17 (75%) sites. One of perfluorinated compounds (PFOA) occurred at 68% of sites, whilst one of illicit drugs (Methamphetamine) was found at 61% of sites. The highest number of contaminants found in one POCIS at a single monitoring site was 111. The concentrations varied from nanograms to thousands of nanograms per sampler. Emerging contaminants occurring in highest concentrations (> 1000 ng/sampler) were BP-4 and PBSA (UV blockers), caffeine, DEET (insect repellent), imidacloprid (insecticide), telmisartan (hypertension drug) and tramadol (analgesic). Monitoring in the Czech Republic has demonstrated that many target compounds enter river waters and a number of these compounds reach high concentrations.

Spectroscopic detection of pharmaceutical compounds from an aflatoxigenic strain of Aspergillus parasiticus.

PubMed

Basaran, P; Demirbas, R M

2010-08-20

Polar and non-polar secondary metabolites as well as phenolic compounds of Aspergillus parasiticus grown on hazelnut were analyzed by high-resolution high performance liquid chromatography-mass spectroscopy and fourier transform infrared spectroscopy. Several novel and beneficial compounds such as dibutyl phthalate, pyrogallol, fumagillol, italicic acid and sorbicillin were identified from A. parasiticus for the first time. Some of these compounds have the potential to be used in pharmaceutical industry. Copyright 2009 Elsevier GmbH. All rights reserved.

Basics of Compounding: 3D Printing: Pharmacy Applications, Part 3: Compounding, Formulation Considerations, and the Future.

PubMed

Allen, Loyd V

2017-01-01

3D printing is a standard tool in the automotive, aerospace, and consumer goods in industry and is gaining traction in pharmaceutical manufacturing, which has introduced a new element into dosage form development. This article, which represents part 3 of a 3-part article on the topic of 3D printing, discusses the compounding, formulation considerations, and the future of 3D printing. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Assessing the removal of pharmaceuticals and personal care products in a full-scale activated sludge plant.

PubMed

Salgado, R; Marques, R; Noronha, J P; Carvalho, G; Oehmen, A; Reis, M A M

2012-06-01

This study aimed to investigate the removal mechanisms of pharmaceutical active compounds (PhACs) and musks in a wastewater treatment plant (WWTP). Biological removal and adsorption in the activated sludge tank as well as the effect of UV radiation used for disinfection purposes were considered when performing a mass balance on the WWTP throughout a 2-week sampling campaign. Solid-phase extraction (SPE) was carried out to analyse the PhACs in the influent and effluent samples. Ultrasonic solvent extraction was used before SPE for PhACs analysis in sludge samples. PhAC extracts were analysed by LC-MS. Solid-phase microextraction of liquid and sludge samples was used for the analysis of musks, which were detected by GC-MS. The fluxes of the most abundant compounds (13 PhACs and 5 musks) out of 79 compounds studied were used to perform the mass balance on the WWTP. Results show that incomplete removal of diclofenac, the compound that was found in the highest abundance, was observed via biodegradation and adsorption, and that UV photolysis was the main removal mechanism for this compound. The effect of adsorption to the secondary sludge was often negligible for the PhACs, with the exceptions of diclofenac, etofenamate, hydroxyzine and indapamide. However, the musks showed a high level of adsorption to the sludge. UV radiation had an important role in reducing the concentration of some of the target compounds (e.g. diclofenac, ibuprofen, clorazepate, indapamide, enalapril and atenolol) not removed in the activated sludge tank. The main removal mechanism of PhACs and musks studied in the WWTP was most often biological (45%), followed by adsorption (33%) and by UV radiation (22%). In the majority of the cases, the WWTP achieved >75% removal of the most detected PhACs and musks, with the exception of diclofenac.

Effects of pH and cationic and nonionic surfactants on the adsorption of pharmaceuticals to a natural aquifer material.

PubMed

Hari, Ajai C; Paruchuri, Rajiv A; Sabatini, David A; Kibbey, Tohren C G

2005-04-15

A wide range of pharmaceutical compounds have been identified in the environment, and their presence is a topic of growing concern, both for human and ecological health. Adsorption to aquifer materials and sediments is an important factor influencing the fate and transport of pharmaceutical compounds in the environment. Surfactants and other amphiphiles are known to influence the adsorption of many compounds and may be present in the environment from wastewaters or other sources. The work described here examines the adsorption of four pharmaceutical compounds, acetaminophen, carbamazepine, nalidixic acid, and norfloxacin, in the presence of a natural aquifer material. Adsorption was studied as a function of pH and in the presence and absence of two surfactants, cetylpyridinium chloride (CPC), a cationic surfactant, and Tergitol NP9, an ethoxylated nonionic surfactant. In the absence of surfactants, results indicate a 1-2 orders of magnitude variation in adsorption affinity with changing pH for each of the two quinolone pharmaceuticals (nalidixic acid and norfloxacin) but no measurable adsorption for carbamazepine or acetaminophen. In the presence of surfactants, adsorption of acetaminophen and carbamazepine was enhanced to extents consistent with compound hydrophobicity, while adsorption of nalidixic acid and norfloxacin was not. At high pH values, the anionic species of nalidixic acid exhibited enhanced adsorption in the presence of the cationic surfactant, CPC.

Radiation chemistry of salicylic and methyl substituted salicylic acids: Models for the radiation chemistry of pharmaceutical compounds

NASA Astrophysics Data System (ADS)

Ayatollahi, Shakiba; Kalnina, Daina; Song, Weihua; Turks, Maris; Cooper, William J.

2013-11-01

Salicylic acid and its derivatives are components of many medications and moieties found in numerous pharmaceutical compounds. They have been used as models for various pharmaceutical compounds in pharmacological studies, for the treatment of pharmaceuticals and personal care products (PPCPs), and, reactions with natural organic matter (NOM). In this study, the radiation chemistry of benzoic acid, salicylic acid and four methyl substituted salicylic acids (MSA) is reported. The absolute bimolecular reaction rate constants for hydroxyl radical reaction with benzoic and salicylic acids as well as 3-methyl-, 4-methyl-, 5-methyl-, and 6-methyl-salicylic acid were determined (5.86±0.54)×109, (1.07±0.07)×1010, (7.48±0.17)×109, (7.31±0.29)×109, (5.47±0.25)×109, (6.94±0.10)×109 (M-1 s-1), respectively. The hydrated electron reaction rate constants were measured (3.02±0.10)×109, (8.98±0.27)×109, (5.39±0.21)×109, (4.33±0.17)×109, (4.72±0.15)×109, (1.42±0.02)×109 (M-1 s-1), respectively. The transient absorption spectra for the six model compounds were examined and their role as model compounds for the radiation chemistry of pharmaceuticals investigated.

Analysis of pharmaceuticals in wastewater and removal using a membrane bioreactor

PubMed Central

Radjenovic, Jelena; Barceló, Damiá

2006-01-01

Much attention has recently been devoted to the life and behaviour of pharmaceuticals in the water cycle. In this study the behaviour of several pharmaceutical products in different therapeutic categories (analgesics and anti-inflammatory drugs, lipid regulators, antibiotics, etc.) was monitored during treatment of wastewater in a laboratory-scale membrane bioreactor (MBR). The results were compared with removal in a conventional activated-sludge (CAS) process in a wastewater-treatment facility. The performance of an MBR was monitored for approximately two months to investigate the long-term operational stability of the system and possible effects of solids retention time on the efficiency of removal of target compounds. Pharmaceuticals were, in general, removed to a greater extent by the MBR integrated system than during the CAS process. For most of the compounds investigated the performance of MBR treatment was better (removal rates >80%) and effluent concentrations of, e.g., diclofenac, ketoprofen, ranitidine, gemfibrozil, bezafibrate, pravastatin, and ofloxacin were steadier than for the conventional system. Occasionally removal efficiency was very similar, and high, for both treatments (e.g. for ibuprofen, naproxen, acetaminophen, paroxetine, and hydrochlorothiazide). The antiepileptic drug carbamazepine was the most persistent pharmaceutical and it passed through both the MBR and CAS systems untransformed. Because there was no washout of biomass from the reactor, high-quality effluent in terms of chemical oxygen demand (COD), ammonium content (N-NH4), total suspended solids (TSS), and total organic carbon (TOC) was obtained. PMID:17115140

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation.

PubMed

Patil, Hemlata; Tiwari, Roshan V; Repka, Michael A

2016-02-01

Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.

Quality investigation of hydroxyprogesterone caproate active pharmaceutical ingredient and injection

PubMed Central

Chollet, John L.; Jozwiakowski, Michael J.

2012-01-01

The purpose of this study was to investigate the quality of hydroxyprogesterone caproate (HPC) active pharmaceutical ingredient (API) sources that may be used by compounding pharmacies, compared to the FDA-approved source of the API; and to investigate the quality of HPC injection samples obtained from compounding pharmacies in the US, compared to the FDA-approved product (Makena®). Samples of API were obtained from every source confirmed to be an original manufacturer of the drug for human use, which were all companies in China that were not registered with FDA. Eight of the ten API samples (80%) did not meet the impurity specifications required by FDA for the API used in the approved product. One API sample was found to not be HPC at all; additional laboratory testing showed that it was glucose. Thirty samples of HPC injection obtained from com pounding pharmacies throughout the US were also tested, and eight of these samples (27%) failed to meet the potency requirement listed in the USP monograph for HPC injection and/or the HPLC assay. Sixteen of the thirty injection samples (53%) exceeded the impurity limit setforthe FDA-approved drug product. These results confirm the inconsistency of compounded HPC Injections and suggest that the risk-benefit ratio of using an unapproved compounded preparation, when an FDA-approved drug product is available, is not favorable. PMID:22329865

Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection

PubMed Central

Dyall, Julie; Coleman, Christopher M.; Hart, Brit J.; Venkataraman, Thiagarajan; Holbrook, Michael R.; Kindrachuk, Jason; Johnson, Reed F.; Olinger, Gene G.; Jahrling, Peter B.; Laidlaw, Monique; Johansen, Lisa M.; Lear-Rooney, Calli M.; Glass, Pamela J.; Hensley, Lisa E.

2014-01-01

Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for in vivo studies as well as incorporation into ongoing clinical studies. PMID:24841273

Nature as a source of metabolites with cholinesterase-inhibitory activity: an approach to Alzheimer's disease treatment.

PubMed

Pinho, Brígida R; Ferreres, Federico; Valentão, Patrícia; Andrade, Paula B

2013-12-01

Alzheimer's disease (AD) is the most common cause of dementia, being responsible for high healthcare costs and familial hardships. Despite the efforts of researchers, no treatment able to delay or stop AD progress exists. Currently, the available treatments are only symptomatic, cholinesterase inhibitors being the most widely used drugs. Here we describe several natural compounds with anticholinesterase (acetylcholinesterase and butyrylcholinesterase) activity and also some synthetic compounds whose structures are based on those of natural compounds. Galantamine and rivastigmine are two cholinesterase inhibitors used in therapeutics: galantamine is a natural alkaloid that was extracted for the first time from Galanthus nivalis L., while rivastigmine is a synthetic alkaloid, the structure of which is modelled on that of natural physostigmine. Alkaloids include a high number of compounds with anticholinesterases activity at the submicromolar range. Quinones and stilbenes are less well studied regarding cholinesterase inhibition, although some of them, such as sargaquinoic acid or (+)-α-viniferin, show promising activity. Among flavonoids, flavones and isoflavones are the most potent compounds. Xanthones and monoterpenes are generally weak cholinesterase inhibitors. Nature is an almost endless source of bioactive compounds. Several natural compounds have anticholinesterase activity and others can be used as leader compounds for the synthesis of new drugs. © 2013 Royal Pharmaceutical Society.

Curvularin and dehydrocurvularin as phytotoxic constituents from curvularia intermedia infecting pandanus amaryllifolius

USDA-ARS?s Scientific Manuscript database

Microbes are good sources of biologically active compounds that can be used as pharmaceuticals and agrochemicals. As part of our continuous efforts in search for biopesticides from natural sources, a fungus was isolated from leaves of Pandanus amaryllifolius that showed severe necrosis. This fungus ...

AntiArthritis Therapies 2005.

PubMed

Braddock, Martin

2005-04-01

This meeting, hosted by Visiongain and B2B conferences, comprised approximately 35 delegates, predominantly from the pharmaceutical industry, and promoted interactive discussion. It covered a broad range of drug discovery and development activities, ranging from preclinical studies with compounds requiring further optimisation, through to launched drugs used in the treatment of arthritis today.

A systems biology approach to investigate the antimicrobial activity of oleuropein

USDA-ARS?s Scientific Manuscript database

Oleuropein and its hydrolysis products are olive phenolic compounds that have antimicrobial effects on a variety of pathogens, with the potential to be utilized in food and pharmaceutical products. While the existing research is mainly focused on individual genes or enzymes that are regulated by ole...

Multifunctional ligand for use as a diagnostic or therapeutic pharmaceutical

DOEpatents

Katti, K.V.; Volkert, W.A.; Ketring, A.R.; Singh, P.R.

1996-05-14

A compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical are revealed. The ligand comprises either a phosphorous or germanium core and at least two hydrazine groups forming a ligand for bonding to a metal extending from the phosphorous or germanium core.

Synthesis and Biological Evaluation of Thiosemicarbazide Derivatives Endowed with High Activity toward Mycobacterium Bovis.

PubMed

Sardari, Soroush; Feizi, Samaneh; Rezayan, Ali Hossein; Azerang, Parisa; Shahcheragh, Seyyed Mohammad; Ghavami, Ghazaleh; Habibi, Azizollah

2017-01-01

Thiosemicarbazides are potent intermediates for the synthesis of pharmaceutical and bioactive materials and thus, they are used extensively in the field of medicinal chemistry. The imine bond (-N=CH-) in this compounds are useful in organic synthesis, in particular for the preparation of heterocycles and non-natural β-aminoacids. In this paper the synthesis of some new thiosemicarbazide derivatives by condensation reaction of various aldehydes or ketones with 4-phenylthiosemicarbazide or thiosemicarbazide is reported. This synthesis method has the advantages of high yields and good bioactivity. The structures of these compounds were confirmed by IR, mass, 1 H NMR, 13 C NMR, and single-crystal X-ray diffraction studies. All of these compounds were tested for their in-vitro anti-mycobacterial activity. The influence of the functional group and position of substituent on anti-bacterial activity of compounds is investigated too. The preliminary results indicated that all of the tested compounds showed good activity against the test organism. The compounds 11 and 30 showed the highest anti-tubercular activity (0.39 μg/mL). This synthesis method has the advantages of high yields and good bioactivity.

Therapeutic Phytogenic Compounds for Obesity and Diabetes

PubMed Central

Jung, Hee Soong; Lim, Yun; Kim, Eun-Kyoung

2014-01-01

Natural compounds have been used to develop drugs for many decades. Vast diversities and minimum side effects make natural compounds a good source for drug development. However, the composition and concentrations of natural compounds can vary. Despite this inconsistency, half of the Food and Drug Administration (FDA)-approved pharmaceuticals are natural compounds or their derivatives. Therefore, it is essential to continuously investigate natural compounds as sources of new pharmaceuticals. This review provides comprehensive information and analysis on natural compounds from plants (phytogenic compounds) that may serve as anti-obesity and/or anti-diabetes therapeutics. Our growing understanding and further exploration of the mechanisms of action of the phytogenic compounds may afford opportunities for development of therapeutic interventions in metabolic diseases. PMID:25421245

Activated persulfate for organic chemical degradation: A review.

PubMed

Matzek, Laura W; Carter, Kimberly E

2016-05-01

Activated persulfate reactions have widespread application for groundwater and environmental remediation, as many of these reactions involve destruction of environmental contaminants. Within the last five years, knowledge of activated persulfate degradation reactions has grown to include novel means of activating persulfate for enhanced removal of organic species. These current studies cover a long list of organic analytes, including pharmaceuticals, pesticides, halogenated compounds and dyes. An extensive review of recently published experimental parameters and results for the destruction of organic compounds via activated persulfate is presented. Focus is placed on emerging methodologies and manipulation of traditional activation techniques. Knowledge gaps are identified and discussed, as despite the number of publications on this subject, more broad-reaching guidelines are needed for optimizing applications of activated persulfate in water treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Concurrent suppression of NF-κB, p38 MAPK and reactive oxygen species formation underlies the effect of a novel compound isolated from Curcuma comosa Roxb. in LPS-activated microglia.

PubMed

Jiamvoraphong, Nittaya; Jantaratnotai, Nattinee; Sanvarinda, Pantip; Tuchinda, Patoomratana; Piyachaturawat, Pawinee; Thampithak, Anusorn; Sanvarinda, Pimtip

2017-07-01

We investigated the molecular mechanisms underlying the effect of (3S)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol, also known as compound 092, isolated from Curcuma comosa Roxb on the production of pro-inflammatory mediators and oxidative stress in lipopolysaccharide (LPS)-activated highly aggressive proliferating immortalized (HAPI) microglial cell lines. Nitric oxide (NO) production was determined using the Griess reaction, and reverse transcription polymerase chain reaction was used to measure the expression of inducible nitric oxide synthase (iNOS) mRNA. Western blotting was used to determine the levels of pro-inflammatory mediators and their related upstream proteins. Compound 092 suppressed NO production and iNOS expression in LPS-stimulated HAPI cells. These effects originated from the ability of compound 092 to attenuate the activation of nuclear factor (NF)-κB as determined by the reduction in p-NF-κB and p-IκB kinase (IKK) protein levels. Compound 092 also significantly lowered LPS-activated intracellular reactive oxygen species production and p38 mitogen-activated protein kinase (MAPK) activation. Compound 092 suppresses microglial activation through attenuation of p38 MAPK and NF-κB activation. Compound 092 thus holds the potential to treat neurodegenerative disorders associated with neuroinflammation and oxidative stress. © 2017 Royal Pharmaceutical Society.

Advanced oxidation process-mediated removal of pharmaceuticals from water: A review.

PubMed

Kanakaraju, Devagi; Glass, Beverley D; Oelgemöller, Michael

2018-08-01

Pharmaceuticals, which are frequently detected in natural and wastewater bodies as well as drinking water have attracted considerable attention, because they do not readily biodegrade and may persist and remain toxic. As a result, pharmaceutical residues pose on-going and potential health and environmental risks. To tackle these emerging contaminants, advanced oxidation processes (AOPs) such as photo-Fenton, sonolysis, electrochemical oxidation, radiation and ozonation etc. have been applied to remove pharmaceuticals. These processes utilize the high reactivity of hydroxyl radicals to progressively oxidize organic compounds to innocuous products. This review provides an overview of the findings from recent studies, which have applied AOPs to degrade pharmaceutical compounds. Included is a discussion that links various factors of TiO 2 -mediated photocatalytic treatment to its effectiveness in degrading pharmaceutical residues. This review furthermore highlights the success of AOPs in the removal of pharmaceuticals from different water matrices and recommendations for future studies are outlined. Copyright © 2018 Elsevier Ltd. All rights reserved.

Novel inhibitors of HIV discovered among existing classes of pharmaceutical compounds indicated for unrelated clinical indications.

PubMed

Kucherov, I I; Rytik, P G; Podol'skaya, I A; Mistryukova, L O; Korjev, M O

2009-01-01

In vitro screening of 307 drugs with various clinical indications (cardiotropic, neurotropic, antibacterial, etc.) has revealed 6 compounds which displayed remarkable antiretroviral activity. Three of these drugs had a tendency to have undesirable side effects and were thus excluded from further consideration. Remaining three, i.e., Xantinol Nicotinate, Tardiferon, and Trental may become valid candidates for inclusion into antiviral regimens such as HAART. In vitro tests have shown that xantinol and trental display synergistic effect with azidothymidine, inhibit the replication AZT-resistant strains of HIV, and have no competing undesirable activities. These compounds should be evaluated in safety studies to determine optimal doses for patients with HIV. If these studies confirm in vitro results these compounds may become valid candidates as safe and affordable means to be added into the arsenal of antiretroviral drugs.

Biodegradation of pharmaceuticals in hospital wastewater by a hybrid biofilm and activated sludge system (Hybas).

PubMed

Escolà Casas, Mònica; Chhetri, Ravi Kumar; Ooi, Gordon; Hansen, Kamilla M S; Litty, Klaus; Christensson, Magnus; Kragelund, Caroline; Andersen, Henrik R; Bester, Kai

2015-10-15

Hospital wastewater contributes a significant input of pharmaceuticals into municipal wastewater. The combination of suspended activated sludge and biofilm processes, as stand-alone or as hybrid process (hybrid biofilm and activated sludge system (Hybas™)) has been suggested as a possible solution for hospital wastewater treatment. To investigate the potential of such a hybrid system for the removal of pharmaceuticals in hospital wastewater a pilot plant consisting of a series of one activated sludge reactor, two Hybas™ reactors and one moving bed biofilm reactor (MBBR) has been established and adapted during 10 months of continuous operation. After this adaption phase batch and continuous experiments were performed for the determination of degradation of pharmaceuticals. Removal of organic matter and nitrification mainly occurred in the first reactor. Most pharmaceuticals were removed significantly. The removal of pharmaceuticals (including X-ray contrast media, β-blockers, analgesics and antibiotics) was fitted to a single first-order kinetics degradation function, giving degradation rate constants from 0 to 1.49 h(-1), from 0 to 7.78 × 10(-1)h(-1), from 0 to 7.86 × 10(-1)h(-1) and from 0 to 1.07 × 10(-1)h(-1) for first, second, third and fourth reactors respectively. Generally, the highest removal rate constants were found in the first and third reactors while the lowest were found in the second one. When the removal rate constants were normalized to biomass amount, the last reactor (biofilm only) appeared to have the most effective biomass in respect to removing pharmaceuticals. In the batch experiment, out of 26 compounds, 16 were assessed to degrade more than 20% of the respective pharmaceutical within the Hybas™ train. In the continuous flow experiments, the measured removals were similar to those estimated from the batch experiments, but the concentrations of a few pharmaceuticals appeared to increase during the first treatment step. Such increase could be attributed to de-conjugation or formation from other metabolites. Copyright © 2015 Elsevier B.V. All rights reserved.

Hospital effluents as a source of emerging pollutants: An overview of micropollutants and sustainable treatment options

NASA Astrophysics Data System (ADS)

Verlicchi, P.; Galletti, A.; Petrovic, M.; Barceló, D.

2010-08-01

SummaryHospital wastewaters contain a variety of toxic or persistent substances such as pharmaceuticals, radionuclides, solvents and disinfectants for medical purposes in a wide range of concentrations due to laboratory and research activities or medicine excretion. Most of these compounds belong to the so called emerging contaminants; quite often unregulated pollutants which may be candidates for future regulation depending on research on their potential health effects and monitoring of their occurrence. Their main characteristic is that they do not need to persist in the environment to cause negative effects since their high transformation/removal rates can be compensated for by their continuous introduction into the environment. Some of these compounds, most of them pharmaceuticals and personal care products may also be present in urban wastewaters. Their concentrations in the effluents may vary from ng L -1 to μg L -1. In this paper, hospital effluents and urban wastewaters are compared in terms of quali-quantitative characteristics. On the basis of an in-depth survey: (i) hospital average specific daily water consumptions (L patient -1 day -1) are evaluated and compared to urban ones (L person -1 day -1), (ii) conventional parameters concentrations in hospital effluents are compared to urban ones and (iii) main pharmaceuticals and other emerging compounds contents are compared in the two wastewaters. Finally, an overview of the removal capacity of the different treatments is reported.

Thermophilic and alkaliphilic Actinobacteria: biology and potential applications

PubMed Central

Shivlata, L.; Satyanarayana, Tulasi

2015-01-01

Microbes belonging to the phylum Actinobacteria are prolific sources of antibiotics, clinically useful bioactive compounds and industrially important enzymes. The focus of the current review is on the diversity and potential applications of thermophilic and alkaliphilic actinobacteria, which are highly diverse in their taxonomy and morphology with a variety of adaptations for surviving and thriving in hostile environments. The specific metabolic pathways in these actinobacteria are activated for elaborating pharmaceutically, agriculturally, and biotechnologically relevant biomolecules/bioactive compounds, which find multifarious applications. PMID:26441937

Occurrence of pharmaceutical contaminants and screening of treatment alternatives for southeastern Louisiana.

PubMed

Boyd, G R; Grimm, D A

2001-12-01

Recent studies conducted in Germany, Switzerland, Denmark, Brazil, Canada, the United States, and elsewhere indicate that low-level concentrations of pharmaceuticals and personal-care products (PPCPs) and their metabolites may be widespread contaminants in our aquatic environment. The persistence of pharmaceutical contaminants has been attributed to (1) human consumption of drugs and subsequent discharges from sewage treatment plants, and (2) veterinary use of drugs and nonpoint discharges from agricultural runoff. Contamination of water resources by these compounds, particularly endocrine disrupting chemicals (EDCs), is emerging as an international environmental concern. The long-term effects of continuous, low-level exposure to PPCPs is not well understood. Preliminary data for raw water samples collected from the Mississippi River and Lake Pontchartrain, Louisiana, are summarized. Three PPCP compounds (clofibric acid, naproxen, and estrone) were analyzed using solid-phase extraction, derivatization, and GC/MS. Batch experiments also were conducted to determine equilibrium capacity of activated carbon for clofibric acid. Preliminary results indicate the occurrence of the selected PPCP contaminants in raw water samples at or near method-detection limits. For batch equilibrium experiments, preliminary results indicate that activated carbon potentially can be used to remove clofibric acid from water. More research is needed to develop rapid and reliable methods for PPCP analysis and to determine the effectiveness of treatment processes for removal of PPCP contaminants in water.

Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action †

PubMed Central

Mayer, Alejandro M. S.; Rodríguez, Abimael D.; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

2017-01-01

The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998–2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products. In addition, 75 marine compounds were reported to have antidiabetic and anti-inflammatory activities and affect the immune and nervous system. Finally, 69 marine compounds were shown to display miscellaneous mechanisms of action which could contribute to novel pharmacological classes. Thus, in 2012–2013, the preclinical marine natural product pharmacology pipeline provided novel pharmacology and lead compounds to the clinical marine pharmaceutical pipeline, and contributed significantly to potentially novel therapeutic approaches to several global disease categories. PMID:28850074

Late-Stage Functionalization of Arylacetic Acids by Photoredox-Catalyzed Decarboxylative Carbon-Heteroatom Bond Formation.

PubMed

Sakakibara, Yota; Ito, Eri; Fukushima, Tomohiro; Murakami, Kei; Itami, Kenichiro

2018-05-02

The rapid transformation of pharmaceuticals and agrochemicals enables access to unexplored chemical space and thus has accelerated the discovery of novel bioactive molecules. Because arylacetic acids are regarded as key structures in bioactive compounds, new transformations of these structures could contribute to drug/agrochemical discovery and chemical biology. This work reports carbon-nitrogen and carbon-oxygen bond formation through the photoredox-catalyzed decarboxylation of arylacetic acids. The reaction shows good functional group compatibility without pre-activation of the nitrogen- or oxygen-based coupling partners. Under similar reaction conditions, carbon-chlorine bond formation was also feasible. This efficient derivatization of arylacetic acids makes it possible to synthesize pharmaceutical analogues and bioconjugates of pharmaceuticals and natural products. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermal stability of synthetic thyroid hormone l-thyroxine and l-thyroxine sodium salt hydrate both pure and in pharmaceutical formulations.

PubMed

Ledeţi, Ionuţ; Ledeţi, Adriana; Vlase, Gabriela; Vlase, Titus; Matusz, Petru; Bercean, Vasile; Şuta, Lenuţa-Maria; Piciu, Doina

2016-06-05

In this paper, the thermal stability of pure l-thyroxine (THY) and l-thyroxine sodium salt hydrate (THYSS) vs. two pharmaceutical solid formulations commercialized on both Romanian and European market (with a content of 100μg, respectively 200μg THYSS per tablet) were investigated. In order to determine whether the presence of excipients affects the thermal stability of the active pharmaceutical ingredient (API), the preliminary study of thermal stability in air atmosphere was completed with an in-depth solid-state kinetic study. By kinetic analysis, the non-isothermal degradation of the selected active pharmaceutical ingredients vs. the solid formulation with strength of 200μg THYSS per tablet was investigated. Isoconversional methods (Kissinger-Akahira-Sunose, Flynn-Wall-Ozawa and Friedman) were employed for the estimation of activation energies values, at five different heating rates, β=5, 7, 10, 12 and 15°Cmin(-1). Also, a fourth method was applied in the processing of data, namely NPK, allowing an objective separation in the physical and chemical processes that contribute to the thermal degradation of the selected compounds. A discussion of thermal stability from the kinetic point of view is also presented. Copyright © 2016 Elsevier B.V. All rights reserved.

Discovery of Novel Saponins from the Viscera of the Sea Cucumber Holothuria lessoni

PubMed Central

Bahrami, Yadollah; Zhang, Wei; Franco, Chris

2014-01-01

Sea cucumbers, sometimes referred to as marine ginseng, produce numerous compounds with diverse functions and are potential sources of active ingredients for agricultural, nutraceutical, pharmaceutical and cosmeceutical products. We examined the viscera of an Australian sea cucumber Holothuria lessoni Massin et al. 2009, for novel bioactive compounds, with an emphasis on the triterpene glycosides, saponins. The viscera were extracted with 70% ethanol, and this extract was purified by a liquid-liquid partition process and column chromatography, followed by isobutanol extraction. The isobutanol saponin-enriched mixture was further purified by high performance centrifugal partition chromatography (HPCPC) with high purity and recovery. The resultant purified polar samples were analyzed using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)/MS and electrospray ionization mass spectrometry (ESI-MS)/MS to identify saponins and characterize their molecular structures. As a result, at least 39 new saponins were identified in the viscera of H. lessoni with a high structural diversity, and another 36 reported triterpene glycosides, containing different aglycones and sugar moieties. Viscera samples have provided a higher diversity and yield of compounds than observed from the body wall. The high structural diversity and novelty of saponins from H. lessoni with potential functional activities presents a great opportunity to exploit their applications for industrial, agricultural and pharmaceutical use. PMID:24821624

Nonribosomal peptides and polyketides of Burkholderia: new compounds potentially implicated in biocontrol and pharmaceuticals.

PubMed

Esmaeel, Qassim; Pupin, Maude; Jacques, Philippe; Leclère, Valérie

2017-05-25

Bacteria belonging to the genus Burkholderia live in various ecological niches and present a significant role in the environments through the excretion of a wide variety of secondary metabolites including modular nonribosomal peptides (NRPs) and polyketides (PKs). These metabolites represent a widely distributed biomedically and biocontrol important class of natural products including antibiotics, siderophores, and anticancers as well as biopesticides that are considered as a novel source that can be used to defend ecological niche from competitors and to promote plant growth. The aim of this review is to present all NRPs produced or potentially produced by strains of Burkholderia, as NRPs represent a major source of active compounds implicated in biocontrol. The review is a compilation of results from a large screening we have performed on 48 complete sequenced genomes available in NCBI to identify NRPS gene clusters, and data found in the literature mainly because some interesting compounds are produced by strains not yet sequenced. In addition to NRPs, hybrids NRPs/PKs are also included. Specific features about biosynthetic gene clusters and structures of the modular enzymes responsible for the synthesis, the biological activities, and the potential uses in agriculture and pharmaceutical of NRPs and hybrids NRPs/PKs will also be discussed.

Setting local rank constraints by orthogonal projections for image resolution analysis: application to the determination of a low dose pharmaceutical compound.

PubMed

Boiret, Mathieu; de Juan, Anna; Gorretta, Nathalie; Ginot, Yves-Michel; Roger, Jean-Michel

2015-09-10

Raman chemical imaging provides chemical and spatial information about pharmaceutical drug product. By using resolution methods on acquired spectra, the objective is to calculate pure spectra and distribution maps of image compounds. With multivariate curve resolution-alternating least squares, constraints are used to improve the performance of the resolution and to decrease the ambiguity linked to the final solution. Non negativity and spatial local rank constraints have been identified as the most powerful constraints to be used. In this work, an alternative method to set local rank constraints is proposed. The method is based on orthogonal projections pretreatment. For each drug product compound, raw Raman spectra are orthogonally projected to a basis including all the variability from the formulation compounds other than the product of interest. Presence or absence of the compound of interest is obtained by observing the correlations between the orthogonal projected spectra and a pure spectrum orthogonally projected to the same basis. By selecting an appropriate threshold, maps of presence/absence of compounds can be set up for all the product compounds. This method appears as a powerful approach to identify a low dose compound within a pharmaceutical drug product. The maps of presence/absence of compounds can be used as local rank constraints in resolution methods, such as multivariate curve resolution-alternating least squares process in order to improve the resolution of the system. The method proposed is particularly suited for pharmaceutical systems, where the identity of all compounds in the formulations is known and, therefore, the space of interferences can be well defined. Copyright © 2015 Elsevier B.V. All rights reserved.

Emerging pharmaceutical therapies for COPD.

PubMed

Lakshmi, Sowmya P; Reddy, Aravind T; Reddy, Raju C

2017-01-01

COPD, for which cigarette smoking is the major risk factor, remains a worldwide burden. Current therapies provide only limited short-term benefit and fail to halt progression. A variety of potential therapeutic targets are currently being investigated, including COPD-related proinflammatory mediators and signaling pathways. Other investigational compounds target specific aspects or complications of COPD such as mucus hypersecretion and pulmonary hypertension. Although many candidate therapies have shown no significant effects, other emerging therapies have improved lung function, pulmonary hypertension, glucocorticoid sensitivity, and/or the frequency of exacerbations. Among these are compounds that inhibit the CXCR2 receptor, mitogen-activated protein kinase/Src kinase, myristoylated alanine-rich C kinase substrate, selectins, and the endothelin receptor. Activation of certain transcription factors may also be relevant, as a large retrospective cohort study of COPD patients with diabetes found that the peroxisome proliferator-activated receptor γ (PPARγ) agonists rosiglitazone and pioglitazone were associated with reduced COPD exacerbation rate. Notably, several therapies have shown efficacy only in identifiable subgroups of COPD patients, suggesting that subgroup identification may become more important in future treatment strategies. This review summarizes the status of emerging therapeutic pharmaceuticals for COPD and highlights those that appear most promising.

Emerging pharmaceutical therapies for COPD

PubMed Central

Lakshmi, Sowmya P; Reddy, Aravind T; Reddy, Raju C

2017-01-01

COPD, for which cigarette smoking is the major risk factor, remains a worldwide burden. Current therapies provide only limited short-term benefit and fail to halt progression. A variety of potential therapeutic targets are currently being investigated, including COPD-related proinflammatory mediators and signaling pathways. Other investigational compounds target specific aspects or complications of COPD such as mucus hypersecretion and pulmonary hypertension. Although many candidate therapies have shown no significant effects, other emerging therapies have improved lung function, pulmonary hypertension, glucocorticoid sensitivity, and/or the frequency of exacerbations. Among these are compounds that inhibit the CXCR2 receptor, mitogen-activated protein kinase/Src kinase, myristoylated alanine-rich C kinase substrate, selectins, and the endothelin receptor. Activation of certain transcription factors may also be relevant, as a large retrospective cohort study of COPD patients with diabetes found that the peroxisome proliferator-activated receptor γ (PPARγ) agonists rosiglitazone and pioglitazone were associated with reduced COPD exacerbation rate. Notably, several therapies have shown efficacy only in identifiable subgroups of COPD patients, suggesting that subgroup identification may become more important in future treatment strategies. This review summarizes the status of emerging therapeutic pharmaceuticals for COPD and highlights those that appear most promising. PMID:28790817

Bitterness prediction in-silico: A step towards better drugs.

PubMed

Bahia, Malkeet Singh; Nissim, Ido; Niv, Masha Y

2018-02-05

Bitter taste is innately aversive and thought to protect against consuming poisons. Bitter taste receptors (Tas2Rs) are G-protein coupled receptors, expressed both orally and extra-orally and proposed as novel targets for several indications, including asthma. Many clinical drugs elicit bitter taste, suggesting the possibility of drugs re-purposing. On the other hand, the bitter taste of medicine presents a major compliance problem for pediatric drugs. Thus, efficient tools for predicting, measuring and masking bitterness of active pharmaceutical ingredients (APIs) are required by the pharmaceutical industry. Here we highlight the BitterDB database of bitter compounds and survey the main computational approaches to prediction of bitter taste based on compound's chemical structure. Current in silico bitterness prediction methods provide encouraging results, can be constantly improved using growing experimental data, and present a reliable and efficient addition to the APIs development toolbox. Copyright © 2017 Elsevier B.V. All rights reserved.

Dual catalysis for enantioselective convergent synthesis of enantiopure vicinal amino alcohols.

PubMed

Ye, Chen-Xi; Melcamu, Yared Yohannes; Li, Heng-Hui; Cheng, Jiang-Tao; Zhang, Tian-Tian; Ruan, Yuan-Ping; Zheng, Xiao; Lu, Xin; Huang, Pei-Qiang

2018-01-29

Enantiopure vicinal amino alcohols and derivatives are essential structural motifs in natural products and pharmaceutically active molecules, and serve as main chiral sources in asymmetric synthesis. Currently known asymmetric catalytic protocols for this class of compounds are still rare and often suffer from limited scope of substrates, relatively low regio- or stereoselectivities, thus prompting the development of more effective methodologies. Herein we report a dual catalytic strategy for the convergent enantioselective synthesis of vicinal amino alcohols. The method features a radical-type Zimmerman-Traxler transition state formed from a rare earth metal with a nitrone and an aromatic ketyl radical in the presence of chiral N,N'-dioxide ligands. In addition to high level of enantio- and diastereoselectivities, our synthetic protocol affords advantages of simple operation, mild conditions, high-yielding, and a broad scope of substrates. Furthermore, this protocol has been successfully applied to the concise synthesis of pharmaceutically valuable compounds (e.g., ephedrine and selegiline).

Enzyme-assistant extraction (EAE) of bioactive components: a useful approach for recovery of industrially important metabolites from seaweeds: a review.

PubMed

Wijesinghe, W A J P; Jeon, You-Jin

2012-01-01

Over the years, the biological activities of seaweeds could have gained a considerable research interest because of their specific functional compounds, which may not be available in land plants. Thus, efforts at discovery of novel metabolites from seaweeds over the past years have yielded a considerable amount of new active compounds. In addition, studies about the extraction of active compounds from natural products have attracted special attention in the last recent years. Potent biologically active compounds of seaweeds have been demonstrated to play a significant role in prevention of certain degenerative diseases such as cancer, inflammation, arthritis, diabetes and hypertension. Therefore, seaweed derived active components, whose immense biochemical diversity looks like to become a rich source of novel chemical entities for the use as functional ingredients in many industrial applications such as functional foods, pharmaceuticals and cosmeceuticals. Thus, the interest in the extraction of active compounds from seaweeds is obvious. However, the physical and chemical barriers of the plant material become the key drawbacks of such extraction process. Therefore, enhanced release and recovery of active compounds attached to the cells have been addressed. Taken together, the aim of this communication is to discuss the potential use of enzyme treatment as a tool to improve the extraction efficiency of bioactive compounds from seaweeds. Copyright © 2011 Elsevier B.V. All rights reserved.

Analytical Validation of Accelerator Mass Spectrometry for Pharmaceutical Development: the Measurement of Carbon-14 Isotope Ratio.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keck, B D; Ognibene, T; Vogel, J S

2010-02-05

Accelerator mass spectrometry (AMS) is an isotope based measurement technology that utilizes carbon-14 labeled compounds in the pharmaceutical development process to measure compounds at very low concentrations, empowers microdosing as an investigational tool, and extends the utility of {sup 14}C labeled compounds to dramatically lower levels. It is a form of isotope ratio mass spectrometry that can provide either measurements of total compound equivalents or, when coupled to separation technology such as chromatography, quantitation of specific compounds. The properties of AMS as a measurement technique are investigated here, and the parameters of method validation are shown. AMS, independent of anymore » separation technique to which it may be coupled, is shown to be accurate, linear, precise, and robust. As the sensitivity and universality of AMS is constantly being explored and expanded, this work underpins many areas of pharmaceutical development including drug metabolism as well as absorption, distribution and excretion of pharmaceutical compounds as a fundamental step in drug development. The validation parameters for pharmaceutical analyses were examined for the accelerator mass spectrometry measurement of {sup 14}C/C ratio, independent of chemical separation procedures. The isotope ratio measurement was specific (owing to the {sup 14}C label), stable across samples storage conditions for at least one year, linear over 4 orders of magnitude with an analytical range from one tenth Modern to at least 2000 Modern (instrument specific). Further, accuracy was excellent between 1 and 3 percent while precision expressed as coefficient of variation is between 1 and 6% determined primarily by radiocarbon content and the time spent analyzing a sample. Sensitivity, expressed as LOD and LLOQ was 1 and 10 attomoles of carbon-14 (which can be expressed as compound equivalents) and for a typical small molecule labeled at 10% incorporated with {sup 14}C corresponds to 30 fg equivalents. AMS provides an sensitive, accurate and precise method of measuring drug compounds in biological matrices.« less

Competitive sorption of atenolol, trimetoprim, carbamazepine and sulfamethoxazole in three soil types

NASA Astrophysics Data System (ADS)

Kočárek, Martin; Kodešová, Radka; Klement, Aleš; Golovko, Oksana; Fér, Miroslav; Nikodem, Antonín; Vondráčková, Lenka; Jakšík, Ondřej; Grabic, Roman

2016-04-01

Transport of human and veterinary pharmaceuticals in soils and consequent ground-water contamination are influenced by many factors, including compound sorption on soil particles and dissipation. Batch sorption experiment for 9 soils (3 soil types with 3 (Greyic Phaeozem on loess), 4 (Haplic Luvisol on loess) and 2 (Haplic Cambisol on gneiss) horizons) and mixture of 4 pharmaceuticals (atenolol, trimetoprim, carbamazepine and sulfamethoxazole) was performed to study competitive sorption of compounds in each soil sample. Sorption affinities and dissipation half-lives of all compounds in topsoils were previously studied by Kodešová et al. (2015 and 2016). Ten grams of dry soil was placed directly into the plastic centrifuge tubes and 20 ml of solution of a known pharmaceutical concentration was added. The same concentrations (0.5, 1, 2.5, 5 and 10 mg/l) were used for all compounds. Three replicates of each concentration were applied for each soil. Tube was shaken for 24 h using the shaking apparatus at 20 C. After shaking, the analyzed soil suspension was centrifuged for 10 min at 6,000 rotations per minute. The actual initial and final equilibrium pharmaceutical concentrations were measured using two-dimensional liquid chromatography-tandem mass spectrometry LC/LC-MS/MS using isotope dilution and internal standard methods. The pharmaceutical concentration adsorbed on soil particles was calculated using the initial and final (i.e. after incubation) pharmaceutical concentrations. The Freundlich equations were used to fit data points of the measured adsorption isotherms. In the case of carbamazepine (neutral form) and sulfamethoxazole (partly negatively charged) sorption affinity of compounds decrease with soil depth. On the other hand in the case of atenolol and trimethoprim (both positively charged) compound sorption affinity was not depth dependent. Data obtained for top soils were compared with sorption affinities for single compounds published by (Kodešová et al., 2015). While sorption affinities of atenolol, trimethoprim and carbamazepine due to compound competition decrease, sorption affinity of sulfamethoxazole increased. Pearson product moment correlation coefficient and p-value were used to evaluate relationships between sorption coefficients and soil properties. Kodešová, R., Grabic, R., Kočárek, M., Klement, A., Golovko, O., Fér, M., Nikodem, A., Jakšík, O. (2015a): Pharmaceuticals' sorptions relative to properties of thirteen different soils. Science of the Total Environment, 511, 435-443. Kodešová, R., Kočárek, M., Klement, A., Golovko, O., Koba, O., Fér, M., Nikodem, A., Vondráčková, L., Jakšík, O., Grabic, R. (2016): An analysis of the dissipation of pharmaceuticals under thirteen different soil conditions. Science of the Total Environment, 544, 369-381.

Occurrence and removal of pharmaceuticals in wastewater treatment plants at the Spanish Mediterranean area of Valencia.

PubMed

Gracia-Lor, Emma; Sancho, Juan V; Serrano, Roque; Hernández, Félix

2012-04-01

A survey on the presence of pharmaceuticals in urban wastewater of a Spanish Mediterranean area (Castellon province) was carried out. The scope of the study included a wide variety of pharmaceuticals belonging to different therapeutical classes. For this purpose, 112 samples, including influent and effluent wastewater, from different conventional wastewater treatment plants were collected. Two monitoring programmes were carried out along several seasons. The first was in June 2008 and January 2009, and the second in April and October 2009. During the first monitoring, the occurrence of 20 analytes in 84 urban wastewater samples (influent and effluent) was studied. The selection of these pharmaceuticals was mainly based on consumption. From these, 17 compounds were detected in the samples, with analgesics and anti-inflammatories, cholesterol lowering statin drugs and lipid regulators being the most frequently detected groups. 4-Aminoantipyrine, bezafibrate, diclofenac, gemfibrozil, ketoprofen, naproxen and venlafaxine were the compounds most frequently found. In the highlight of these results, the number of analytes was increased up to around 50. A lot of antibiotic compounds were added to the target list as they were considered "priority pharmaceuticals" due to their more potential hazardous effects in the aquatic environment. Data obtained during the second monitoring programme (spring and autumn) corroborated the results from the first one (summer and winter). Analgesics and anti-inflammatories, lipid regulators together with quinolone and macrolide antibiotics were the most abundant pharmaceuticals. Similar median concentrations were found over the year and seasonal variation was not clearly observed. The removal efficiency of pharmaceuticals in the wastewater treatment plants was roughly evaluated. Our results indicated that elimination of most of the selected compounds occurred during the treatment process of influent wastewater, although it was incomplete. Copyright © 2011 Elsevier Ltd. All rights reserved.

Trends in active pharmaceutical ingredient salt selection based on analysis of the Orange Book database.

PubMed

Paulekuhn, G Steffen; Dressman, Jennifer B; Saal, Christoph

2007-12-27

The Orange Book database published by the U.S. Drug and Food Administration (FDA) was analyzed for the frequency of occurrence of different counterions used for the formation of pharmaceutical salts. The data obtained from the present analysis of the Orange Book are compared to reviews of the Cambridge Structural Database (CSD) and of the Martindale "The Extra Pharmacopoeia". As well as showing overall distributions of counterion usage, results are broken down into 5-year increments to identify trends in counterion selection. Chloride ions continue to be the most frequently utilized anionic counterions for the formation of salts as active pharmaceutical ingredients (APIs), while sodium ions are most widely utilized for the formation of salts starting from acidic molecules. A strong trend toward a wider variety of counterions over the past decade is observed. This trend can be explained by a stronger need to improve physical chemical properties of research and development compounds.

[Microbial secondary metabolites as potential reserve of pharmaceuticals].

PubMed

Orlova, T I; Bulgakova, V G; Polin, A N

2014-01-01

The major characteristics of new bioactive microbial secondary metabolites are summarized in the review. A wide range of new molecular targets are implicated in discovery of new nonantibiotic compounds with some other pharmacological activities (noninfectious diseases). Microorganisms represent fascinating resources due to their production of novel products with broad spectra of bioactivities.

Rhodium-Catalyzed Boron Arylation of 1,2-Azaborines**

PubMed Central

Rudebusch, Gabriel E.; Zakharov, Lev N.; Liu, Shih-Yuan

2013-01-01

A Sn-phony in B! BN isosteres of biphenyl compounds are prepared through Rh-catalyzed cross-coupling between 2-chloro-1,2-azaborines and arylstannanes (see scheme). The synthetic method should enable investigations of structure–activity relationships (SARs) by expanding the chemical space of the pharmaceutically relevant biphenyl structure through BN/CC isosterism. PMID:23832871

High throughput screening of active pharmaceutical ingredients by UPLC.

PubMed

Al-Sayah, Mohammad A; Rizos, Panagiota; Antonucci, Vincent; Wu, Naijun

2008-07-01

Ultra performance LC (UPLC) was evaluated as an efficient screening approach to facilitate method development for drug candidates. Three stationary phases were screened: C-18, phenyl, and Shield RP 18 with column dimensions of 150 mm x 2.1 mm, 1.7 microm, which should theoretically generate 35,000 plates or 175% of the typical column plate count of a conventional 250 mm x 4.6 mm, 5 microm particle column. Thirteen different active pharmaceutical ingredients (APIs) were screened using this column set with a standardized mobile-phase gradient. The UPLC method selectivity results were compared to those obtained for these compounds via methods developed through laborious trial and error screening experiments using numerous conventional HPLC mobile and stationary phases. Peak capacity was compared for columns packed with 5 microm particles and columns packed with 1.7 microm particles. The impurities screened by UPLC were confirmed by LC/MS. The results demonstrate that simple, high efficiency UPLC gradients are a feasible and productive alternative to more conventional multiparametric chromatographic screening approaches for many compounds in the early stages of drug development.

2013 Survey of Iowa groundwater and evaluation of public well vulnerability classifications for contaminants of emerging concern

USGS Publications Warehouse

Hruby, Claire E.; Libra, Robert D.; Fields, Chad L.; Kolpin, Dana W.; Hubbard, Laura E.; Borchardt, Mark R.; Spencer, Susan K.; Wichman, Michael D.; Hall, Nancy; Schueller, Michael D.; Furlong, Edward T.; Weyer, Peter J.

2015-01-01

Studies in Iowa have long documented the vulnerability of wells with less than 50 feet (15 meters) of confining materials above the source aquifer to contamination from nitrate and various pesticides. Recent studies in Wisconsin have documented the occurrence of viruses in untreated groundwater, even in wells considered to have little vulnerability to contamination from near-surface activities. In addition, sensitive methods have become available for analyses of pharmaceuticals and pesticides. This study represents the first comprehensive examination of contaminants of emerging concern in Iowa’s groundwater conducted to date, and one of the first conducted in the United States. Raw groundwater samples were collected from 66 public supply wells during the spring of 2013, when the state was recovering from drought conditions. Samples were analyzed for 206 chemical and biological parameters; including 20 general water-quality parameters and major ions, 19 metals, 5 nutrients, 10 virus groups, 3 species of pathogenic bacteria, 5 microbial indicators, 108 pharmaceuticals, 35 pesticides and pesticide degradates, and tritium. The wells chosen for this study represent a diverse range of ages, depths, confining material thicknesses, pumping rates, and land use settings. The most commonly detected contaminant group was pesticide compounds, which were present in 41% of the samples. As many as 6 pesticide compounds were found together in a sample, most of which were chloroacetanilide degradates. While none of the measured concentrations of pesticide compounds exceeded current benchmark levels, several of these compounds are listed on the U.S. Environmental Protection Agency’s Contaminant Candidate List and could be subject to drinking water standards in the future. Despite heavy use in the past decade, glyphosate was not detected, and its metabolite, aminomethylphosphonic acid, was only detected in two of 60 wells tested (3%) at the detection limit of 0.02 μg/L. Pharmaceutical compounds were detected in 35% of 63 samples. Of the 14 pharmaceuticals detected, six had reported concentrations above the method reporting limit, with the maximum reported concentration of 826 ng/L for acetaminophen. Diphenhydramine was the only pharmaceutical to have two detections above the reporting limit, at 24.5 and 145 ng/L. Eight pharmaceuticals had confirmed detections at concentrations below the method reporting limit. Caffeine was the most frequently detected pharmaceutical compound (25%), followed by the caffeine metabolite, 1,7- dimethylxanthine (16%).  Microorganisms were detected in 21% of the wells using quantitative polymerase chain reaction methodologies. The most frequently detected microorganism was the pepper mild mottle virus (PMMV), a plant pathogen found in human waste. PMMV was detected in 17% of samples at concentrations ranging from 0.4 to 6.38 gene copies per liter. GII norovirus, human polyomavirus, bovine polyomavirus, and Campylobacter were also detected, while adenovirus, enterovirus, GI norovirus, swine hepatitis E, Salmonella, and enterohemmorhagic E. coli were not detected. No correlations were found between viruses or pathogenic bacteria and microbial indicators. Wells with less than 50 feet (15 meters) of confining material were shown to have greater incidence of surface-related contaminants; however, significant relationships (p<0.05) between confining layer thickness and contaminants were only found for nitrate and herbicides.

Removal of pharmaceuticals during drinking water treatment.

PubMed

Ternes, Thomas A; Meisenheimer, Martin; McDowell, Derek; Sacher, Frank; Brauch, Heinz-Jürgen; Haist-Gulde, Brigitte; Preuss, Gudrun; Wilme, Uwe; Zulei-Seibert, Ninette

2002-09-01

The elimination of selected pharmaceuticals (bezafibrate, clofibric acid, carbamazepine, diclofenac) during drinking water treatment processes was investigated at lab and pilot scale and in real waterworks. No significant removal of pharmaceuticals was observed in batch experiments with sand under natural aerobic and anoxic conditions, thus indicating low sorption properties and high persistence with nonadapted microorganisms. These results were underscored by the presence of carbamazepine in bank-filtrated water with anaerobic conditions in a waterworks area. Flocculation using iron(III) chloride in lab-scale experiments (Jar test) and investigations in waterworks exhibited no significant elimination of the selected target pharmaceuticals. However, ozonation was in some cases very effective in eliminating these polar compounds. In lab-scale experiments, 0.5 mg/L ozone was shown to reduce the concentrations of diclofenac and carbamazepine by more than 90%, while bezafibrate was eliminated by 50% with a 1.5 mg/L ozone dose. Clofibric acid was stable even at 3 mg/L ozone. Under waterworks conditions, similar removal efficiencies were observed. In addition to ozonation, filtration with granular activated carbon (GAC) was very effective in removing pharmaceuticals. Except for clofibric acid, GAC in pilot-scale experiments and waterworks provided a major elimination of the pharmaceuticals under investigation.

Identification and quantification of 12 pharmaceuticals in water collected from milking parlors: Food safety implications.

PubMed

Veiga-Gómez, María; Nebot, Carolina; Franco, Carlos Manuel; Miranda, Jose Manuel; Vázquez, Beatriz; Cepeda, Alberto

2017-05-01

The introduction of drug residues into the food chain and their presence in drinking water has been recently investigated. The aim of this work was to monitor the presence of 19 active drugs in water samples collected from milking parlors of dairy farms located in Galicia (northwest Spain), one of the main Spanish milking areas. Overall, 65% of the samples tested positive for at least one of the compounds analyzed. A total of 12 drugs were measured, with concentrations ranging between 17 and 3,941 ng/L. Considering that a mixture of compounds may contribute to the overall effect of each compound and might increase or reduce its toxicity, it should be noted that 29% of the samples tested contained more than one pharmaceutical. To date, the effects of the continuous consumption of these mixtures of drugs in water or milk are unknown; however, antimicrobials may affect the human gut microbiota or have toxic effects in sensitive individuals. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Tracing origins of complex pharmaceutical preparations using surface desorption atmospheric pressure chemical ionization mass spectrometry.

PubMed

Zhang, Xinglei; Jia, Bin; Huang, Keke; Hu, Bin; Chen, Rong; Chen, Huanwen

2010-10-01

A novel strategy to trace the origins of commercial pharmaceutical products has been developed based on the direct chemical profiling of the pharmaceutical products by surface desorption atmospheric pressure chemical ionization mass spectrometry (DAPCI-MS). Besides the unambiguous identification of active drug components, various compounds present in the matrixes are simultaneously detected without sample pretreatment, providing valuable information for drug quality control and origin differentiation. Four sources of commercial amoxicillin products made by different manufacturers have been successfully differentiated. This strategy has been extended to secerning six sources of Liuwei Dihuang Teapills, which are herbal medicine preparations with extremely complex matrixes. The photolysis status of chemical drug products and the inferior natural herd medicine products prepared with different processes (e.g., extra heating) were also screened using the method reported here. The limit of detection achieved in the MS/MS experiments was estimated to be 1 ng/g for amoxicillin inside the capsule product. Our experimental data demonstrate that DAPCI-MS is a useful tool for rapid pharmaceutical analysis, showing promising perspectives for tracking the entire pharmaceutical supply chain to prevent counterfeit intrusions.

Bioaccumulation and trophic dilution of human pharmaceuticals across trophic positions of an effluent-dependent wadeable stream

PubMed Central

Du, Bowen; Haddad, Samuel P.; Luek, Andreas; Scott, W. Casan; Saari, Gavin N.; Kristofco, Lauren A.; Connors, Kristin A.; Rash, Christopher; Rasmussen, Joseph B.; Chambliss, C. Kevin; Brooks, Bryan W.

2014-01-01

Though pharmaceuticals are increasingly observed in a variety of organisms from coastal and inland aquatic systems, trophic transfer of pharmaceuticals in aquatic food webs have not been reported. In this study, bioaccumulation of select pharmaceuticals was investigated in a lower order effluent-dependent stream in central Texas, USA, using isotope dilution liquid chromatography–tandem mass spectrometry (MS). A fish plasma model, initially developed from laboratory studies, was tested to examine observed versus predicted internal dose of select pharmaceuticals. Pharmaceuticals accumulated to higher concentrations in invertebrates relative to fish; elevated concentrations of the antidepressant sertraline and its primary metabolite desmethylsertraline were observed in the Asian clam, Corbicula fluminea, and two unionid mussel species. Trophic positions were determined from stable isotopes (δ15N and δ13C) collected by isotope ratio-MS; a Bayesian mixing model was then used to estimate diet contributions towards top fish predators. Because diphenhydramine and carbamazepine were the only target compounds detected in all species examined, trophic magnification factors (TMFs) were derived to evaluate potential trophic transfer of both compounds. TMFs for diphenhydramine (0.38) and carbamazepine (1.17) indicated neither compound experienced trophic magnification, which suggests that inhalational and not dietary exposure represented the primary route of uptake by fish in this effluent-dependent stream. PMID:25313153

Determination of a broad spectrum of pharmaceuticals and endocrine disruptors in biofilm from a waste water treatment plant-impacted river.

PubMed

Huerta, B; Rodriguez-Mozaz, S; Nannou, C; Nakis, L; Ruhí, A; Acuña, V; Sabater, S; Barcelo, D

2016-01-01

Wastewater treatment plants (WWTPs) are one of the main sources of pharmaceuticals and endocrine disrupting compounds in freshwater ecosystems, and several studies have reported bioaccumulation of these compounds in different organisms in those ecosystems. River biofilms are exceptional indicators of pollution, but very few studies have focused on the accumulation of these emerging contaminants. The objectives of this study were first to develop an efficient analytical methodology for the simultaneous analysis of 44 pharmaceuticals and 13 endocrine disrupting compounds in biofilm, and second, to assess persistence, distribution, and bioaccumulation of these contaminants in natural biofilms inhabiting a WWTP-impacted river. The method is based on pressurized liquid extraction, purification by solid-phase extraction, and analysis by ultra performance liquid chromatography coupled to a mass spectrometer (UPLC-MS/MS) in tandem. Recoveries for pharmaceuticals were 31-137%, and for endocrine disruptors 32-93%. Method detection limits for endocrine disruptors were in the range of 0.2-2.4 ng g(-1), and for pharmaceuticals, 0.07-6.7 ng g(-1). A total of five endocrine disruptors and seven pharmaceuticals were detected in field samples at concentrations up to 100 ng g(-1). Copyright © 2015. Published by Elsevier B.V.

Influence of activated carbon preloading by EfOM fractions from treated wastewater on adsorption of pharmaceutically active compounds.

PubMed

Hu, Jingyi; Shang, Ran; Heijman, Bas; Rietveld, Luuk

2016-05-01

In this study, the preloading effects of different fractions of wastewater effluent organic matter (EfOM) on the adsorption of trace-level pharmaceutically active compounds (PhACs) onto granular activated carbon (GAC) were investigated. A nanofiltration (NF) membrane was employed to separate the EfOM by size, and two GACs with distinct pore structures were chosen for comparison. The results showed that preloading with EfOM substantially decreased PhAC uptake of the GACs; however, comparable PhAC adsorption capacities were achieved on GACs preloaded by feed EfOM and the NF-permeating EfOM. This indicates that: (1) the NF-rejected, larger EfOM molecules with an expectation to block the PhAC adsorption pores exerted little impact on the adsorbability of PhACs; (2) the smaller EfOM molecules present in the NF permeate contributed mainly to the decrease in PhAC uptake, mostly due to site competition. Of the two examined GACs, the wide pore-size-distributed GAC was found to be more susceptible to EfOM preloading than the microporous GAC. Furthermore, among the fourteen investigated PhACs, the negatively charged hydrophilic PhACs were generally subjected to a greater EfOM preloading impact. Copyright © 2016 Elsevier Ltd. All rights reserved.

Use and practice of achiral and chiral supercritical fluid chromatography in pharmaceutical analysis and purification.

PubMed

Lemasson, Elise; Bertin, Sophie; West, Caroline

2016-01-01

The interest of pharmaceutical companies for complementary high-performance chromatographic tools to assess a product's purity or enhance this purity is on the rise. The high-throughput capability and economic benefits of supercritical fluid chromatography, but also the "green" aspect of CO2 as the principal solvent, render supercritical fluid chromatography very attractive for a wide range of pharmaceutical applications. The recent reintroduction of new robust instruments dedicated to supercritical fluid chromatography and the progress in stationary phase technology have also greatly benefited supercritical fluid chromatography. Additionally, it was shown several times that supercritical fluid chromatography could be orthogonal to reversed-phase high-performance liquid chromatography and could efficiently compete with it. Supercritical fluid chromatography is an adequate tool for small molecules of pharmaceutical interest: synthetic intermediates, active pharmaceutical ingredients, impurities, or degradation products. In this review, we first discuss about general chromatographic conditions for supercritical fluid chromatography analysis to better suit compounds of pharmaceutical interest. We also discuss about the use of achiral and chiral supercritical fluid chromatography for analytical purposes and the recent applications in these areas. The use of preparative supercritical fluid chromatography by pharmaceutical companies is also covered. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Natural products possessing protein tyrosine phosphatase 1B (PTP1B) inhibitory activity found in the last decades

PubMed Central

Jiang, Cheng-shi; Liang, Lin-fu; Guo, Yue-wei

2012-01-01

This article provides an overview of approximately 300 secondary metabolites with inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), which were isolated from various natural sources or derived from synthetic process in the last decades. The structure-activity relationship and the selectivity of some compounds against other protein phosphatases were also discussed. Potential pharmaceutical applications of several PTP1B inhibitors were presented. PMID:22941286

Informing the Human Plasma Protein Binding of Environmental Chemicals by Machine Learning in the Pharmaceutical Space: Applicability Domain and Limits of Predictability.

PubMed

Ingle, Brandall L; Veber, Brandon C; Nichols, John W; Tornero-Velez, Rogelio

2016-11-28

The free fraction of a xenobiotic in plasma (F ub ) is an important determinant of chemical adsorption, distribution, metabolism, elimination, and toxicity, yet experimental plasma protein binding data are scarce for environmentally relevant chemicals. The presented work explores the merit of utilizing available pharmaceutical data to predict F ub for environmentally relevant chemicals via machine learning techniques. Quantitative structure-activity relationship (QSAR) models were constructed with k nearest neighbors (kNN), support vector machines (SVM), and random forest (RF) machine learning algorithms from a training set of 1045 pharmaceuticals. The models were then evaluated with independent test sets of pharmaceuticals (200 compounds) and environmentally relevant ToxCast chemicals (406 total, in two groups of 238 and 168 compounds). The selection of a minimal feature set of 10-15 2D molecular descriptors allowed for both informative feature interpretation and practical applicability domain assessment via a bounded box of descriptor ranges and principal component analysis. The diverse pharmaceutical and environmental chemical sets exhibit similarities in terms of chemical space (99-82% overlap), as well as comparable bias and variance in constructed learning curves. All the models exhibit significant predictability with mean absolute errors (MAE) in the range of 0.10-0.18F ub . The models performed best for highly bound chemicals (MAE 0.07-0.12), neutrals (MAE 0.11-0.14), and acids (MAE 0.14-0.17). A consensus model had the highest accuracy across both pharmaceuticals (MAE 0.151-0.155) and environmentally relevant chemicals (MAE 0.110-0.131). The inclusion of the majority of the ToxCast test sets within the AD of the consensus model, coupled with high prediction accuracy for these chemicals, indicates the model provides a QSAR for F ub that is broadly applicable to both pharmaceuticals and environmentally relevant chemicals.

The Effect of Dynamic Evaporation Rates on the Mobility of Pharmaceuticals in Unsaturated Environments

NASA Astrophysics Data System (ADS)

Normile, H.; Papelis, C.; Kibbey, T. C. G.

2015-12-01

The focus of this work was on investigating how dynamic rates of evaporation affect the fate and transport of pharmaceutical compounds in unsaturated porous media. The environmental processes of saturation and evaporation control local concentrations of contaminants in pore water of porous media. Specifically, the rate of evaporation can affect the identity and extent of solid formation of a pharmaceutical compound. A range of experiments with different evaporation rates were conducted on sand columns saturated with a solution of ciprofloxacin, a fluoroquinolone antibiotic. Experiments were designed to simulate increased and decreased pore-water concentrations of a compound due to evaporation and resaturation, respectively. Results suggest that varied rates of evaporation cause differences in compound adsorption behavior. This result has significant implications for understanding fate and transport within the unsaturated zone. Preliminary models exploring the impact on contaminant mobility are discussed.

Comparative pharmaceutical metabolism by rainbow trout (Oncorhynchus mykiss) liver S9 fractions

EPA Science Inventory

The occurrence of pharmaceuticals in the environment presents a challenge of growing concern. In contrast to many industrial compounds, pharmaceuticals undergo extensive testing prior to their introduction to the environment. In principle, therefore, it may be possible to emplo...

Characterization of ToxCast Phase II compounds disruption of ...

EPA Pesticide Factsheets

The development of multi-well microelectrode array (mwMEA) systems has increased in vitro screening throughput making them an effective method to screen and prioritize large sets of compounds for potential neurotoxicity. In the present experiments, a multiplexed approach was used to determine compound effects on both neural function and cell health in primary cortical networks grown on mwMEA plates following exposure to ~1100 compounds from EPA’s Phase II ToxCast libraries. On DIV 13, baseline activity (40 min) was recorded prior to exposure to each compound at 40 µM. DMSO and the GABAA antagonist bicuculline (BIC) were included as controls on each mwMEA plate. Changes in spontaneous network activity (mean firing rate; MFR) and cell viability (lactate dehydrogenase; LDH and CellTiter Blue; CTB) were assessed within the same well following compound exposure. Activity calls (“hits”) were established using the 90th and 20th percentiles of the compound-induced change in MFR (medians of triplicates) across all tested compounds; compounds above (top 10% of compounds increasing MFR), and below (bottom 20% of compounds decreasing MFR) these thresholds, respectively were considered hits. MFR was altered beyond one of these thresholds by 322 compounds. Four compound categories accounted for 66% of the hits, including: insecticides (e.g. abamectin, lindane, prallethrin), pharmaceuticals (e.g. haloperidol, reserpine), fungicides (e.g. hexaconazole, fenamidone), and h

Determination of selected pharmaceuticals in tap water and drinking water treatment plant by high-performance liquid chromatography-triple quadrupole mass spectrometer in Beijing, China.

PubMed

Cai, Mei-Quan; Wang, Rong; Feng, Li; Zhang, Li-Qiu

2015-02-01

A simultaneous determination method of 14 multi-class pharmaceuticals using solid-phase extraction (SPE) followed by high-performance liquid chromatography-tandem mass spectrometer (HPLC-MS/MS) was established to measure the occurrence and distribution of these pharmaceuticals in tap water and a drinking water treatment plant (DWTP) in Beijing, China. Target compounds included seven anti-inflammatory drugs, two antibacterial drugs, two lipid regulation drugs, one antiepileptic drug, and one hormone. Limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.01 to 1.80 ng/L and 0.05 to 3.00 ng/L, respectively. Intraday and inter-day precisions, recoveries of different matrices, and matrix effects were also investigated. Of the 14 pharmaceutical compounds selected, nine were identified in tap water of Beijing downtown with the concentration up to 38.24 ng/L (carbamazepine), and the concentration levels of detected pharmaceuticals in tap water (<5 ng/L for most pharmaceuticals) were lower than previous studies in other countries. In addition, ten and six pharmaceuticals were measured in raw water and finished water at the concentration ranged from 0.10 to 16.23 and 0.13 to 17.17 ng/L, respectively. Five compounds were detected most frequently in DWTP, namely antipyrine, carbamazepine, isopropylantipyrine, aminopyrine, and bezafibrate. Ibuprofen was found to be the highest concentration pharmaceutical during DWTP, up to 53.30 ng/L. DWTP shows a positive effect on the removal of most pharmaceuticals with 81.2-99.5 % removal efficiencies, followed by carbamazepine with 55.4 % removal efficiency, but it has no effect for removing ibuprofen and bezafibrate.

U.S. Food and Drug Administration Inspections: Guide to a Successful Outcome for 503A Sterile Compounding Pharmacies.

PubMed

Yoch, Doug

2017-01-01

The reasons for which pharmaceutical compounding is the focus of intense state and federal scrutiny are now well known. Compounders are faced with an ever-increasing need to prove, by objective standards, the safety, purity, and potency of the formulations they dispense. They must also demonstrate their compliance with regulations often based on current good compounding practices designed for the pharmaceutical industry. In the U.S. today, rigorous unannounced state and federal inspections of compounding facilities are occurring more and more frequently. To achieve a successful outcome, communicating clearly and effectively with inspectors and having ready access to the information they request are as critical as proving compliance. This article describes the author's experience with an unannounced United States Food and Drug Administration inspection of his 503A compounding facility and his response to the findings. Readers will learn what to expect during such an inspection, how to prepare for that event, and how to achieve an excellent outcome. Those who would like more information about any of the topics presented are invited to contact the author at the address provided at the close of this article. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Pharmaceuticals and endocrine disrupting compounds in U.S. drinking water.

PubMed

Benotti, Mark J; Trenholm, Rebecca A; Vanderford, Brett J; Holady, Janie C; Stanford, Benjamin D; Snyder, Shane A

2009-02-01

The drinking water for more than 28 million people was screened for a diverse group of pharmaceuticals, potential endocrine disrupting compounds (EDCs), and other unregulated organic contaminants. Source water, finished drinking water, and distribution system (tap) water from 19 U.S. water utilities was analyzed for 51 compounds between 2006 and 2007. The 11 most frequently detected compounds were atenolol, atrazine, carbamazepine, estrone, gemfibrozil, meprobamate, naproxen, phenytoin, sulfamethoxazole, TCEP, and trimethoprim. Median concentrations of these compounds were less than 10 ng/L, except for sulfamethoxazole in source water (12 ng/L), TCEP in source water (120 ng/L), and atrazine in source, finished, and distribution system water (32, 49, and 49 ng/L). Atrazine was detected in source waters far removed from agricultural application where wastewater was the only known source of organic contaminants. The occurrence of compounds in finished drinking water was controlled by the type of chemical oxidation (ozone or chlorine) used at each plant. At one drinking water treatment plant, summed monthly concentrations of the detected analytes in source and finished water are reported. Atenolol, atrazine, DEET, estrone, meprobamate, and trimethoprim can serve as indicator compounds representing potential contamination from other pharmaceuticals and EDCs and can gauge the efficacy of treatment processes.

Monitoring of emerging contaminants (pharmaceuticals, Personal Care Products, surfactants and heavy metals) in a quaternary detritic aquifer

NASA Astrophysics Data System (ADS)

Candela, L.; Valdes-Abellan, J.; Jiménez-Martínez, J.

2012-04-01

The presence of 209 emerging compounds, surfactants, priority substances according to the 2008/105/EC Directive, 10 heavy metals and microbiological organisms in blended water and aquifer samples was investigated in a quaternary aquifer. The effects of these compounds over the environment are not clear in many cases, but many of them have been classified as endocrine disruptor compounds, EDC. Their presence in the media is controlled in one hand by their transformation and/or removal rates and, on the other hand, by their continuous release into the media, due to the broad use of these in many human activities (pharmaceuticals, personal care products, pesticides, heavy metals, LAS and others). The attention of this work focusses on the presence and fate of these substances in the vadose zone and the aquifer. The aquifer catchment (81km2) located in SE Spain presents a high natural salinity (with EC values of ~7,500 μS cm-1, and high concentrations of chloride, sulphate and sodium), making it unsuitable to be used as drinking water or irrigation. Two sampling campaigns (February and June 2011) in wells and springs have been carried out top characterize physic-chemical, microbiological and emerging contaminants presence in the aquifer. A total of 209 emerging pollutants grouped into the following classes were analysed: 125 pharmaceutical compounds (Phs), 20 polyaromatic hydrocarbons (PAHs) and Dioxins, 46 pesticides, 3 volatile priority pollutants as well as the most commonly used anionic surfactants were identified for further analysis. Heavy metals included: Cu, Cd, Pb, Hg, Ni, Zn, Sn, Pt, Pd and Tl. Results showed that 39 out of all compounds were detected: 11 pharmaceuticals, 9 PAHs, 19 pesticides, 4 surfactants and 4 heavy metals. Two of the compounds, endosulfan-α and Ni, were detected in concentrations above the allowed regulation. Although results are limited to 2 sampling campaigns, it is important to note that surfactants (LAS), pesticides PAHs and Dioxins were detected in most of the water samples, this indicates the presence of wastewater effluents of urban origin and agricultural impacts. The ubiquitous presence of LAS is related to the low-sorption capacity and its wide variety of applications, ranging from cleaning products to pesticide formulation (among others).

Organically functionalized mesoporous SBA-15 as sorbents for removal of selected pharmaceuticals from water.

PubMed

Bui, Tung Xuan; Kang, Seo-Young; Lee, Sang-Hyup; Choi, Heechul

2011-10-15

Mesoporous silica SBA-15 and its postfunctionalized counterparts with hydroxymethyl (HM-SBA-15), aminopropyl (AP-SBA-15), and trimethylsilyl (TMS-SBA-15) were prepared and characterized by powder X-ray diffraction, N(2) adsorption-desorption measurement, Fourier-transform infrared spectroscopy, and elemental analysis. The removal of a mixture of 12 selected pharmaceuticals was investigated by batch adsorption experiments onto SBA-15 and the grafted materials. SBA-15 showed to have moderate adsorption affinity with amino-containing (atenolol, trimethoprim) and hydrophobic pharmaceuticals, but it displayed minimal adsorption affinity toward hydrophilic compounds. HM-SBA-15 was analogous with SBA-15 in terms of the adsorption efficiency toward all pharmaceuticals. AP-SBA-15 exhibited an increase in the adsorption of two acidic compounds (clofibric acid, diclofenac) but a decrease in the adsorption of estrone and the two amino-containing compounds. Among the grafted materials, TMS-SBA-15 had the highest adsorption affinity toward most pharmaceuticals. Moreover, the adsorption of nine pharmaceuticals to TMS-SBA-15 was significantly higher than that to SBA-15; seven of which showed the removal percentages from 70.6% to 98.9% onto TMS-SBA-15. The number of pharmaceuticals showing high adsorption efficiency onto TMS-SBA-15 did not alter significantly as the pH changed in the range of 5.5-7.6. The results suggest that TMS-SBA-15 is a promising material for the removal of pharmaceuticals from aqueous phase, especially for the treatment of wastewater from drug manufacturers. Copyright © 2011 Elsevier B.V. All rights reserved.

Targeting RORs nuclear receptors by novel synthetic steroidal inverse agonists for autoimmune disorders.

PubMed

Dal Prà, Matteo; Carta, Davide; Szabadkai, Gyorgy; Suman, Matteo; Frión-Herrera, Yahima; Paccagnella, Nicola; Castellani, Giulia; De Martin, Sara; Ferlin, Maria Grazia

2018-05-01

Designing novel inverse agonists of NR RORγt still represents a challenge for the pharmaceutical community to develop therapeutics for treating immune diseases. By exploring the structure of NRs natural ligands, the representative arotenoid ligands and RORs specific ligands share some chemical homologies which can be exploited to design a novel molecular structure characterized by a polycyclic core bearing a polar head and a hydrophobic tail. Compound MG 2778 (8), a cyclopenta[a]phenantrene derivative, was identified as lead compound which was chemically modified at position 2 in order to obtain a small library for preliminary SARs. Cell viability and estrogenic activity of compounds 7, 8, 19a, 30, 31 and 32 were evaluated to attest selectivity. The selected 7, 8, 19a and 31 compounds were assayed in a Gal4 UAS-Luc co-transfection system in order to determine their ability to modulate RORγt activity in a cellular environment. They were evaluated as inverse agonists taken ursolic acid as reference compound. The potency of compounds was lower than that of ursolic acid, but their efficacy was similar. Compound 19a was the most active, significantly reducing RORγt activity at low micromolar concentrations. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Daniel K. Inouye College of Pharmacy Scripts

PubMed Central

Chang, Leng Chee; Sang-ngern, Mayuramas; Pezzuto, John M; Ma, Carolyn

2016-01-01

The Daniel K. Inouye College of Pharmacy, during a historic event in Spring 2016, graduated the first two students in the Pacific region to earn a PhD in pharmaceutical sciences at the University of Hawai‘i at Hilo. The college offers PhD programs in these five disciplines: Cancer Biology, Medicinal Chemistry, Pharmaceutics, Pharmacognosy, and Pharmacology. One of the Pharmacognosy dissertations focused on plant-derived natural products with potential anti-inflammatory and cancer chemopreventive activities. Physalis peruviana (Pp) L. originated in tropical South America. It has become naturalized and is found readily on the Island of Hawai‘i. The edible fruits are commonly known as cape gooseberry or poha in Hawai‘i. In part of our study, three new withanolides, physaperuvin G (1), physaperuvins I–J (2–3), along with four known withanolides, namely, 4β-hydroxywithanolide E (4), withaperuvin C (5), and physalactone (6), coagulin (7) were isolated from the aerial parts of P. peruviana. In addition, two known compounds, phyperunolide F (8), and withanolide S (9), were isolated and identified from the poha berry fruits. The structures and absolute stereochemistry of new compounds from poha were elucidated by several spectroscopy methods: Nuclear Magnetic Resonance (NMR) spectroscopy, X-ray diffraction, and mass spectrometry analyses. All isolated poha compounds (aerial parts and fruits) were evaluated for their anti-inflammatory activity with lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells, and tumor necrosis factor alpha (TNF-α)-activated nuclear factor-kappa B (NF-κB) with transfected human embryonic kidney cells 293. Most of the isolated natural compounds showed activity with these assays. Additional studies were performed with models of colon cancer. Specifically, 4β-hydroxywithanolide E (4HWE) inhibited the growth of colon cancer monolayer and spheroid cultures. The compound induced cell cycle arrest at low concentrations and apoptosis at higher concentrations. These data suggest the ingestion of poha berries may have some effect on the prevalence of colon cancer. Additionally, poha isolates compounds were evaluated for their growth inhibitory effects with U251MG glioblastoma and MDA-MB-231 breast cancer cells that harbor aberrantly-active signal transducer and activation of transcription 3 (STAT3), compared to normal NIH-3T3 mouse fibroblasts. This work has led to the filing of three provisional patents with the University of Hawai‘i Office of Technology Transfer and Economic Development. PMID:27920947

Between pharmaceutical patents and European patients: is a compromise still possible?

PubMed

Garattini, Livio; Padula, Anna

2017-10-01

Pharmaceutical regulation has always attempted to balance the public health objective to make safe and effective drugs available for patients while providing commercial incentives through patents. Here we discuss whether it is still possible to find a balance between the incentives on the supply side and the regulatory framework on the demand side. Areas covered: The current regulatory framework on pharmaceutical exclusivity has been harshly criticized by many experts, arguing about whether it is still fit for public purposes and needs. Here we envisage a different scenario without 'revolutionizing' the whole present system. The main radical change should concern the present management of pharmaceutical patents by introducing a specific agency dedicated to them. Secondly, specific pharmaceutical patents could be restricted to compounds for one (or more) declared indication(s). Thirdly, pharmaceutical patents should be kept only for compounds that start a first clinical trial within five years from the granting date. Expert opinion: We think it is time to reconsider the regulation of pharmaceutical patents in the light of their relevance in terms of public health. New models of enhancing research investments are required for long-term sustainability of public pharmaceutical expenditure and the EU can still play a leading role.

The role of graphene oxide and graphene oxide-based nanomaterials in the removal of pharmaceuticals from aqueous media: a review.

PubMed

Khan, Ayub; Wang, Jian; Li, Jun; Wang, Xiangxue; Chen, Zhongshan; Alsaedi, Ahmed; Hayat, Tasawar; Chen, Yuantao; Wang, Xiangke

2017-03-01

In this review paper, the ill effects of pharmaceuticals (PhAs) on the environment and their adsorption on graphene oxide (GO) and graphene oxide-based (GO-based) nanomaterials have been summarised and discussed. The adsorption of prominent PhAs discussed herein includes beta-blockers (atenolol and propranolol), antibiotics (tetracycline, ciprofloxacin and sulfamethoxazole), pharmaceutically active compounds (carbamazepine) and analgesics such as diclofenac. The adsorption of PhAs strictly depends upon the experimental conditions such as pH, adsorbent and adsorbate concentrations, temperature, ionic strength, etc. To understand the adsorption mechanism and feasibility of the adsorption process, the adsorption isotherms, thermodynamics and kinetic studies were also considered. Except for some cases, GO and its derivatives show excellent adsorption capacities for PhAs, which is crucial for their applications in the environmental pollution cleanup.

Synthesis, crystal structure, cytotoxic, antileishmanial activities and docking studies on N,N‧-(ethane-1,2-diyl)bis(3-methylbenzamide)

NASA Astrophysics Data System (ADS)

Aziz, Hamid; Saeed, Aamer; Jabeen, Farukh; Simpson, Jim; Munawar, Amna; Qasim, Muhammad

2018-03-01

Amide derivatives have gained considerable attention because of their extensive range of biological activities and pharmaceutical applications. The current paper presents the synthesis of N, N‧-(ethane-1,2-diyl) bis (3-methylbenzamide), (I), its molecular and crystal structure and an evaluation of its likely biological activity, including cytotoxicity (LD50 = 37.21 μg/ml) and antileishmanial activity (IC50 = 5.77 μg/ml). Moreover, a docking simulation was used to determine the possible interaction sites of the compound (I) with TryR, an enzyme involved in the redox metabolism of the leishmania parasite. Docking computations demonstrate that the compound established prominent binding interactions with the key residues of the TryR and possess the potential to effectively inhibit the catalytic activities of the enzyme. Thus the results suggest that this compound can serve as a potential scaffold for the treatment of leishmaniasis and deserves further development.

Plant seeds as sources of potential industrial chemicals, pharmaceuticals, and pest control agents.

PubMed

Powell, Richard G

2009-03-27

Investigations of natural products isolated from seeds have resulted in a remarkable variety of compounds having unusual structures. Seeds of many plant species contain uncommon fatty acids and lipids, some of which have found uses in the cosmetic industry or as renewable (non-petroleum based) industrial raw materials. In addition to proteins and energy storage substances such as carbohydrates and lipids, seeds generally contain, or have the ability to produce, protective compounds that are active as plant growth regulators, fungicides, insecticides, and repellents of herbivores; seeds occasionally contain compounds that are toxic to most other organisms. These compounds may also be present in other plant parts, but often are found at higher concentrations in seeds. Other compounds of interest have been associated with plant-endophyte interactions that are of mutual benefit to both organisms. Tests of seed extracts for cytotoxic and antitumor activity, toxicity to insects, and relationships to several animal disease syndromes have been revealing. Examples of compounds isolated from plant seeds that have served as lead compounds for additional research, or that continue to be of interest to researchers in multiple areas, are reviewed.

Potential physiological effects of pharmaceutical compounds in Atlantic salmon (Salmo salar) implied by transcriptomic analysis.

PubMed

Hampel, Miriam; Alonso, Esteban; Aparicio, Irene; Bron, James E; Santos, Juan Luis; Taggart, John B; Leaver, Michael J

2010-05-01

Pharmaceuticals are emerging pollutants widely used in everyday urban activities which can be detected in surface, ground, and drinking waters. Their presence is derived from consumption of medicines, disposal of expired medications, release of treated and untreated urban effluents, and from the pharmaceutical industry. Their growing use has become an alarming environmental problem which potentially will become dangerous in the future. However, there is still a lack of knowledge about long-term effects in non-target organisms as well as for human health. Toxicity testing has indicated a relatively low acute toxicity to fish species, but no information is available on possible sublethal effects. This study provides data on the physiological pathways involved in the exposure of Atlantic salmon as representative test species to three pharmaceutical compounds found in ground, surface, and drinking waters based on the evaluation of the xenobiotic-induced impairment resulting in the activation and silencing of specific genes. Individuals of Atlantic salmon (Salmo salar) parr were exposed during 5 days to environmentally relevant concentrations of three representative pharmaceutical compounds with high consumption rates: the analgesic acetaminophen (54.77+/-34.67 microg L(-1)), the anticonvulsant carbamazepine (7.85+/-0.13 microg L(-1)), and the beta-blocker atenolol (11.08+/-7.98 microg L(-1)). Five immature males were selected for transcriptome analysis in brain tissues by means of a 17k salmon cDNA microarray. For this purpose, mRNA was isolated and reverse-transcribed into cDNA which was labeled with fluorescent dyes and hybridized against a common pool to the arrays. Lists of significantly up- and down-regulated candidate genes were submitted to KEGG (Kyoto Encyclopedia of Genes and Genomes) in order to analyze for induced pathways and to evaluate the usefulness of this method in cases of not completely annotated test organisms. Exposure during 5 days to environmentally relevant concentrations of the selected pharmaceutical compounds acetaminophen, carbamazepine, and atenolol produced differences in the expression of 659, 700, and 480 candidate genes, respectively. KEGG annotation numbers (KO annotations) were obtained for between 26.57% and 33.33% of these differently expressed genes per treatment in comparison to non-exposure conditions. Pathways that showed to be induced did not always follow previously reported targets or metabolic routes for the employed treatments; however, several other pathways have been found (four or more features) to be significantly induced. Energy-related pathways have been altered under exposure in all the selected treatments, indicating a possible energy budget leakage due to additional processes resulting from the exposure to environmental contaminants. Observed induction of pathways may indicate additional processes involved in the mode of action of the selected pharmaceuticals which may not have been detected with conventional methods like quantitative PCR in which only suspected features are analyzed punctually for effects. The employment of novel high-throughput screening techniques in combination with global pathway analysis methods, even if the organism is not completely annotated, allows the examination of a much broader range of candidates for potential effects of exposure at the gene level. The continuously growing number of annotations of representative species relevant for environmental quality testing is facilitating pathway analysis processes for not completely annotated organisms. KEGG has shown to be a useful tool for the analysis of induced pathways from data generated by microarray techniques with the selected pharmaceutical contaminants acetaminophen, carbamazepine, and atenolol, but further studies have to be carried out in order to determine if a similar expression pattern in terms of fold change quantity and pathways is observed after long-term exposure. Together with the information obtained in this study, it will then be possible to evaluate the potential risk that the continuous release of these compounds may have on the environment and ecosystem functioning.

Optimization of a pyrazole hit from FBDD into a novel series of indazoles as ketohexokinase inhibitors.

PubMed

Zhang, Xuqing; Song, Fengbing; Kuo, Gee-Hong; Xiang, Amy; Gibbs, Alan C; Abad, Marta C; Sun, Weimei; Kuo, Lawrence C; Sui, Zhihua

2011-08-15

A series of indazoles have been discovered as KHK inhibitors from a pyrazole hit identified through fragment-based drug discovery (FBDD). The optimization process guided by both X-ray crystallography and solution activity resulted in lead-like compounds with good pharmaceutical properties. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Investigation of biologically active compounds at the Department of Organic Chemistry of University of Debrecen 1992-2009. Part III].

PubMed

Antus, Sándor

2010-01-01

The author briefly reviews the beginning of the carbohydrate chemistry in Hungary with special regard to the results achieved at the Department of Organic Chemistry of University of Debrecen and summarizes the most important synthetic and pharmaceutical results obtained in this field between 1992-2009, part III.

Unsaturated fatty acids lactose esters: cytotoxicity, permeability enhancement and antimicrobial activity.

PubMed

Lucarini, Simone; Fagioli, Laura; Campana, Raffaella; Cole, Hannah; Duranti, Andrea; Baffone, Wally; Vllasaliu, Driton; Casettari, Luca

2016-10-01

Sugar based surfactants conjugated with fatty acid chains are an emerging broad group of highly biocompatible and biodegradable compounds with established and potential future applications in the pharmaceutical, cosmetic and food industries. In this work, we investigated absorption enhancing and antimicrobial properties of disaccharide lactose, monoesterified with unsaturated fatty acids through an enzymatic synthetic approach. After chemical and cytotoxicity characterizations, their permeability enhancing activity was demonstrated using intestinal Caco-2 monolayers through transepithelial electrical resistance (TEER) and permeability studies. The synthesized compounds, namely lactose palmitoleate (URB1076) and lactose nervonate (URB1077), were shown to exhibit antimicrobial activity versus eight pathogenic species belonging to Gram-positive, Gram-negative microorganisms and fungi. Copyright © 2016 Elsevier B.V. All rights reserved.

Spatial Trends of Pharmaceuticals in an Urbanized Estuary: Influence of Wastewater Effluents in Narragansett Bay, RI, USA

EPA Science Inventory

For years, pharmaceuticals have been routinely detected in wastewater treatment plant effluents and freshwater systems. Wastewater effluent serves as a primary source of pharmaceutical compounds to natural waters. Many marine and estuarine systems receive inputs either directly...

Cyclodextrins Based Electrochemical Sensors for Biomedical and Pharmaceutical Analysis.

PubMed

Lenik, Joanna

2017-01-01

Electrochemical sensors are very convenient devices, as they may be used in a lot of fields starting from the food industry to environmental monitoring and medical diagnostics. They offer the values of simple design, reversible and reproducible measurements, as well as ensuring precise and accurate analytical information. Compared with other methods, electrochemical sensors are relatively simple as well as having low costs, which has led to intensive development, especially in the field of medicine and pharmaceuticals within the last decade. Recently, the number of publications covering the determination of aminoacids, dopamine, cholesterol, uric acid, biomarkers, vitamins and other pharmaceutical and biological compounds has significantly increased. Many possible types of such sensors and biosensors have been proposed: owing to the kind of the detection-potentiometric voltametric, amperometry, and the materials that can be used for, e.g. designing molecular architecture of the electrode/solution interface, carbon paste, carbon nanotubes, glass carbon, graphite, graphene, PVC, conductive polymers and/or nanoparticles. The active compounds which provide the complex formation with analyte (in the case of non-current techniques) or activate biomolecules electrochemically by particle recognition and selective preconcentration of analyte on the electrode surface (in the case of current techniques) are the most recently used cyclodextrins. These macrocyclic compounds have the ability to interact with a large diversity of guest particles to form complexes of the type of guest host, for example, with particles from drugs, biomolecules, through their hydrophilic outer surface and lipophilic inner cavities. Cyclodextrins have been the subject of frequent electrochemical studies that focused mostly on both their interactions in a solid state and in solution. The process of preparing of CDs modified electrodes would, consequently, open new avenues for new electrochemical sensors and, therefore, widen their use in biomedical and drug analysis. This review presents information on manufacturing techniques and performances of these sensors and biosensors. The opportunities for these sensors to carry out biomedical and pharmaceutical researches are demonstrated. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Removal of pharmaceutically active compounds from synthetic and real aqueous mixtures and simultaneous disinfection by supported TiO2/UV-A, H2O2/UV-A, and TiO2/H2O2/UV-A processes.

PubMed

Bosio, Morgana; Satyro, Suéllen; Bassin, João Paulo; Saggioro, Enrico; Dezotti, Márcia

2018-05-01

Pharmaceutically active compounds are carried into aquatic bodies along with domestic sewage, industrial and agricultural wastewater discharges. Psychotropic drugs, which can be toxic to the biota, have been detected in natural waters in different parts of the world. Conventional water treatments, such as activated sludge, do not properly remove these recalcitrant substances, so the development of processes able to eliminate these compounds becomes very important. Advanced oxidation processes are considered clean technologies, capable of achieving high rates of organic compounds degradation, and can be an efficient alternative to conventional treatments. In this study, the degradation of alprazolam, clonazepam, diazepam, lorazepam, and carbamazepine was evaluated through TiO 2 /UV-A, H 2 O 2 /UV-A, and TiO 2 /H 2 O 2 /UV-A, using sunlight and artificial irradiation. While using TiO 2 in suspension, best results were found at [TiO 2 ] = 0.1 g L -1 . H 2 O 2 /UV-A displayed better results under acidic conditions, achieving from 60 to 80% of removal. When WWTP was used, degradation decreased around 50% for both processes, TiO 2 /UV-A and H 2 O 2 /UV-A, indicating a strong matrix effect. The combination of both processes was shown to be an adequate approach, since removal increased up to 90%. H 2 O 2 /UV-A was used for disinfecting the aqueous matrices, while mineralization was obtained by TiO 2 -photocatalysis.

Marine Indole Alkaloids

PubMed Central

Netz, Natalie; Opatz, Till

2015-01-01

Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in addition to the action on human enzymes and receptors. The newly isolated indole alkaloids of marine origin since the last comprehensive review in 2003 are reported, and biological aspects will be discussed. PMID:26287214

The use of high-throughput screening techniques to evaluate mitochondrial toxicity.

PubMed

Wills, Lauren P

2017-11-01

Toxicologists and chemical regulators depend on accurate and effective methods to evaluate and predict the toxicity of thousands of current and future compounds. Robust high-throughput screening (HTS) experiments have the potential to efficiently test large numbers of chemical compounds for effects on biological pathways. HTS assays can be utilized to examine chemical toxicity across multiple mechanisms of action, experimental models, concentrations, and lengths of exposure. Many agricultural, industrial, and pharmaceutical chemicals classified as harmful to human and environmental health exert their effects through the mechanism of mitochondrial toxicity. Mitochondrial toxicants are compounds that cause a decrease in the number of mitochondria within a cell, and/or decrease the ability of mitochondria to perform normal functions including producing adenosine triphosphate (ATP) and maintaining cellular homeostasis. Mitochondrial dysfunction can lead to apoptosis, necrosis, altered metabolism, muscle weakness, neurodegeneration, decreased organ function, and eventually disease or death of the whole organism. The development of HTS techniques to identify mitochondrial toxicants will provide extensive databases with essential connections between mechanistic mitochondrial toxicity and chemical structure. Computational and bioinformatics approaches can be used to evaluate compound databases for specific chemical structures associated with toxicity, with the goal of developing quantitative structure-activity relationship (QSAR) models and mitochondrial toxicophores. Ultimately these predictive models will facilitate the identification of mitochondrial liabilities in consumer products, industrial compounds, pharmaceuticals and environmental hazards. Copyright © 2017 Elsevier B.V. All rights reserved.

Bioturbo similarity searching: combining chemical and biological similarity to discover structurally diverse bioactive molecules.

PubMed

Wassermann, Anne Mai; Lounkine, Eugen; Glick, Meir

2013-03-25

Virtual screening using bioactivity profiles has become an integral part of currently applied hit finding methods in pharmaceutical industry. However, a significant drawback of this approach is that it is only applicable to compounds that have been biologically tested in the past and have sufficient activity annotations for meaningful profile comparisons. Although bioactivity data generated in pharmaceutical institutions are growing on an unprecedented scale, the number of biologically annotated compounds still covers only a minuscule fraction of chemical space. For a newly synthesized compound or an isolated natural product to be biologically characterized across multiple assays, it may take a considerable amount of time. Consequently, this chemical matter will not be included in virtual screening campaigns based on bioactivity profiles. To overcome this problem, we herein introduce bioturbo similarity searching that uses chemical similarity to map molecules without biological annotations into bioactivity space and then searches for biologically similar compounds in this reference system. In benchmark calculations on primary screening data, we demonstrate that our approach generally achieves higher hit rates and identifies structurally more diverse compounds than approaches using chemical information only. Furthermore, our method is able to discover hits with novel modes of inhibition that traditional 2D and 3D similarity approaches are unlikely to discover. Test calculations on a set of natural products reveal the practical utility of the approach for identifying novel and synthetically more accessible chemical matter.

Structural Characterization and Evaluation of the Antioxidant Activity of Phenolic Compounds from Astragalus taipaishanensis and Their Structure-Activity Relationship

NASA Astrophysics Data System (ADS)

Pu, Wenjun; Wang, Dongmei; Zhou, Dan

2015-09-01

Eight phenolic compounds were isolated using bio-guided isolation and purified from the roots of Astragalus taipaishanensis Y. C. Ho et S. B. Ho (A. taipaishanensis) for the first time. Their structures were elucidated by ESI-MS, HR-ESI-MS, 1D-NMR and 2D-NMR as 7,2‧-dihydroxy-3‧,4‧-dimethoxy isoflavan (1), formononetin (2), isoliquiritigenin (3), quercetin (4), kaempferol (5), ononin (6), p-hydroxybenzoic acid (7) and vanillic acid (8). Six flavonoids (compounds 1-6) exhibited stronger antioxidant activities (determined by DPPH, ABTS, FRAP and lipid peroxidation inhibition assays) than those of BHA and TBHQ and also demonstrated noticeable protective effects (particularly quercetin and kaempferol) on Escherichia coli under oxidative stress. Additionally, the chemical constituents compared with those of Astragalus membranaceus and the structure-activity relationship of the isolated compounds were both analyzed. The results clearly demonstrated that A. taipaishanensis has the potential to be selected as an alternative medicinal and food plant that can be utilized in health food products, functional tea and pharmaceutical products.

Biological Activities of Extracts from Loquat (Eriobotrya japonica Lindl.): A Review

PubMed Central

Liu, Yilong; Zhang, Wenna; Xu, Changjie; Li, Xian

2016-01-01

Loquat (Eriobotrya japonica Lindl.) is a subtropical fruit tree with high medicinal value native to China. Different organs of loquat have been used historically as folk medicines and this has been recorded in Chinese history for thousands of years. Research shows that loquat extracts contain many antioxidants, and different extracts exhibit bioactivity capable of counteracting inflammation, diabetes, cancer, bacterial infection, aging, pain, allergy and other health issues. Bioactive compounds such as phenolics and terpenoids have been isolated and characterized to provide a better understanding of the chemical mechanisms underlying the biological activities of loquat extracts. As the identification of compounds progresses, studies investigating the in vivo metabolism, bioavailability, and structure–activity relationships, as well as potential toxicity of loquat extracts in animal or cell models are receiving more attention. In addition, genetic studies and breeding of loquat germplasms for high contents of health-benefiting compounds may provide new insight for the loquat industry and research. This review is focused on the main medicinal properties reported and the possible pharmaceutically active compounds identified in different loquat extracts. PMID:27929430

The Development of a Parenteral Pharmaceutical Formulation of a New Class of Compounds of Nitrosourea.

PubMed

Nikolaeva, Ludmila; Oborotova, Natalia; Bunyatyan, Natalia; Zhang, Xi; Sanarova, Ekaterina; Lantsova, Anna; Orlova, Olga; Polozkova, Alevtina

2016-11-01

Despite the rapid development of medical technologies, chemotherapy treatment still occupies an important place in clinical oncology. In this regard, the current research in this area focuses on the synthesis of new highly effective antitumor substances that have minimal side effects and the development of stable pharmaceutical formulations (PF) on their basis. In order to solve this problem, the I. Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences actively sought for original substances, namely, nitrosourea (NU) derivatives, one of the most promising classes of anticancer drugs. As a result of this research, a novel NU derivative was synthesized, namely ormustine, which showed high antitumor activity in preliminary preclinical trials. It is now crucial to develop an ormustine pharmaceutical formulation. Conducted technological studies showed that the most suitable solvent for the drug substance is 0.1 M hydrochloric acid, which ensures its rapid dissolution by ultrasonic treatment. A significant reduction in the concentration of the active ingredient during the storage of the solution required the development of a technique of its lyophilization and the selection of a shaper such as a Kollidon 17 PF. Upon completion of the development of a pharmaceutical formulation of ormustine, its stability after lyophilization was demonstrated, and a sufficient amount of the drug has been acquired for preclinical research.

Behaviour of pharmaceuticals and personal care products in a sewage treatment plant of northwest Spain.

PubMed

Carballa, M; Omil, F; Lema, J M; Llompart, M; García, C; Rodriguez, I; Gómez, M; Ternes, T

2005-01-01

Thirteen pharmaceutical and cosmetic compounds have been surveyed along the different units of a municipal sewage treatment plant (STP) to study their fate across each step and the overall removal efficiency. The STP studied corresponds to a population of approximately 100,000 inhabitants located in Galicia (northwest Spain), including three main sections: pre-treatment (coarse and fine screening, grit and fat removal); primary treatment (sedimentation tanks); and secondary treatment (conventional activated sludge). Among all the substances considered (galaxolide, tonalide, carbamazepine, diazepam, diclofenac, ibuprofen, naproxen, estrone, estradiol, ethinylestradiol, roxitromycin, sulfamethoxazole and iopromide), only significant concentrations were found for two musks (galaxolide and tonalide), two antiphlogistics (ibuprofen and naproxen), two natural estrogens (estrone, estradiol), one antibiotic (sulfamethoxazole) and the X-ray contrast media (iopromide), being the other compounds below the quantification level. In the primary treatment, only the fragrances were partly removed, with efficiencies of 20-50% for galaxolide and tonalide. However, the aerobic treatment caused an important reduction in all compounds detected, between 35 and 75%, with the exception of iopromide. The overall removal efficiency of the STP ranged between 70 and 90% for the fragrances, 45 and 70% for the acidic compounds, around 67% for estradiol and 57% for the antibiotic sulfamethoxazole.

Experimental and density functional theory studies on benzalkonium ibuprofenate, a double active pharmaceutical ingredient.

PubMed

Safna Hussan, K P; Thayyil, M Shahin; Rajan, Vijisha K; Muraleedharan, K

2018-02-01

Molecular aspects of a double active pharmaceutical ingredient in ionic liquid form, benzalkonium ibuprofenate (BaIb), were studied using density functional theory (DFT/B3LYP/6-31+G (d, p)). A detailed discussion on optimized geometry, energy, heat and the enthalpy of BaIb was carried out. The computed vibrational results agree well with the experimental results. The stability and biological activity were compared to the parent drugs on the basis of global descriptive parameters. The electrophilic and nucleophilic sites were pointed out in the MESP structures well evidently. NBO analysis was also done to predict the relative aromaticity, delocalization effects and the contribution towards stabilization energy of the title compound. The information about non-covalent, non-ionic weak interaction between the cation and anion was obtained from the list of Mulliken charges and NBO analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Advanced biological activated carbon filter for removing pharmaceutically active compounds from treated wastewater.

PubMed

Sbardella, Luca; Comas, Joaquim; Fenu, Alessio; Rodriguez-Roda, Ignasi; Weemaes, Marjoleine

2018-04-28

Through their release of effluents, conventional wastewater treatment plants (WWTPs) represent a major pollution point sources for pharmaceutically active compounds (PhACs) in water bodies. The combination of a biological activated carbon (BAC) filter coupled with an ultrafiltration (UF) unit was evaluated as an advanced treatment for PhACs removal at pilot scale. The BAC-UF pilot plant was monitored for one year. The biological activity of the biofilm that developed on the granular activated carbon (GAC) particles and the contribution of this biofilm to the overall removal of PhACs were evaluated. Two different phases were observed during the long-term monitoring of PhACs removal. During the first 9200 bed volumes (BV; i.e., before GAC saturation), 89, 78, 83 and 79% of beta-blockers, psychiatric drugs, antibiotics and a mix of other therapeutic groups were removed, respectively. The second phase was characterized by deterioration of the overall performances during the period between 9200 and 13,800 BV. To quantify the respective contribution of adsorption and biodegradation, a lab-scale setup was operated for four months and highlighted the essential role played by GAC in biofiltration units. Physical adsorption was indeed the main removal mechanism. Nevertheless, a significant contribution due to biological activity was detected for some PhACs. The biofilm contributed to the removal of 22, 25, 30, 32 and 35% of ciprofloxacin, bezafibrate, ofloxacin, azithromycin and sulfamethoxazole, respectively. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

The possibility of obtaining marketing authorization of orphan pharmaceutical compounding preparations: 3,4-DAP for Lambert-Eaton Myasthenic Syndrome.

PubMed

de Wilde, Sofieke; de Jong, Maria G H; Lipka, Alexander F; Guchelaar, Henk-Jan; Schimmel, Kirsten J M

2018-03-01

Pharmaceutical compounding preparations, produced by (hospital) pharmacies, usually do not have marketing authorization. As a consequence, some of these pharmaceutical compounding preparations can be picked-up by a pharmaceutical company to obtain marketing authorization, often leading to price increases. An example is the 3,4-diaminopyridine slow release (3,4-DAP SR) tablets for Lambert-Eaton Myasthenic Syndrome (LEMS). In 2009 marketing authorization was given for the commercial immediate release phosphate salt of the drug, including a fifty-fold price increase compared to the pharmaceutical compounding preparation. Obtaining marketing authorization for 3,4-DAP SR by academia might have been a solution to prevent this price increase. To determine whether the available data of a pharmaceutical compounding preparation with long-term experience in regular care are adequate to obtain marketing authorization, 3,4-DAP SR is used as a case study. A retrospective qualitative case-study was performed. Initially, document analysis was executed by collecting the required data for marketing authorization in general and whether data of Firdapse® and 3,4-DAP SR met these requirements. Secondly, the (non-) available data of the two formulations were compared with each other to determine the differences in availability. At the time of approval, almost all data were available for both Firdapse® and 3,4-DAP SR. Conversely, much of the data used for the approval of Firdapse® originated from the 3,4-DAP immediate release (3,4-DAP IR) formulation. Only two bioequivalence studies and one pharmacology safety study was performed with Firdapse® before marketing authorization application. In conclusion, at time Firdapse® obtained approval, the data available did not differ substantially from 3,4-DAP SR, indicating that approval with 3,4-DAP SR would have been possible. We make a plea for approval of orphan medicinal products developed and manufactured by academic institutions as to keep utilization of these products affordable. Copyright © 2017 Elsevier B.V. All rights reserved.

Cajanus cajan- a source of PPARγ activators leading to anti-inflammatory and cytotoxic effects.

PubMed

Schuster, Roswitha; Holzer, Wolfgang; Doerfler, Hannes; Weckwerth, Wolfram; Viernstein, Helmut; Okonogi, Siriporn; Mueller, Monika

2016-09-14

Cajanus cajan is an important legume crop in the human diet in many parts of the world. Due to its pharmacological properties, C. cajan is, moreover, used in traditional medicine for treating skin diseases, diabetes, inflammatory disorders and various other dysfunctions. In this study, we focused on the role of peroxisome proliferator-activated receptor gamma (PPARγ) as a potential therapeutic target of Cajanus cajan and its main compounds for the treatment of cancer, inflammation and inflammation-related disorders. The anti-inflammatory potential of C. cajan and its bioactive compounds and their cytotoxicity on the human cervical adenocarcinoma cell line HeLa, the human colorectal adenocarcinoma cell line CaCo-2 and the human breast adenocarcinoma cell line MCF-7 were elucidated. C. cajan and its compounds exerted significant anti-inflammatory activity on lipopolysaccharide-stimulated macrophages, showed good cytotoxic effects on the 3 different cancer cell lines and proved PPARγ activity in vitro. The main active compounds were orientin, pinostrobin and vitexin. Cajaninstilbene acid and pinosylvin monomethylether were identified as novel PPARγ activators. Based on these data, C. cajan provides excellent beneficial medicinal attributes and may be used as a potential food or a pharmaceutical supplement.

OCCURRENCE OF SELECTED PHARMACEUTICAL AND NON-PHARMACEUTICAL COMPOUNDS, AND STABLE HYDROGEN AND OXYGEN ISOTOPE RATIOS, IN A RIVERBANK FILTRATION STUDY, PLATTE RIVER, NEBRASKA, 2001 TO 2003, VOLUME 1. DATA SERIES 117.

EPA Science Inventory

Although studied extensively in recent years in Europe, the occurrence of endocrine disrupters and other organic wastewater compounds in the environment in the United States is not well documented. To better understand the efficiency of riverbank filtration with respect to endoc...

Chemical Characteristics, Synthetic Methods, and Biological Potential of Quinazoline and Quinazolinone Derivatives

PubMed Central

2014-01-01

The heterocyclic fused rings quinazoline and quinazolinone have drawn a huge consideration owing to their expanded applications in the field of pharmaceutical chemistry. Quinazoline and quinazolinone are reported for their diversified biological activities and compounds with different substitutions bring together to knowledge of a target with understanding of the molecule types that might interact with the target receptors. Quinazolines and quinazolinones are considered as an important chemical for the synthesis of various physiological significance and pharmacological utilized molecules. Quinazolines and quinazolinone are a large class of biologically active compounds that exhibited broad spectrum of biological activities such as anti-HIV, anticancer, antifungal, antibacterial, antimutagenic, anticoccidial, anticonvulsant, anti-inflammatory, antidepressant, antimalarial, antioxidant, antileukemic, and antileishmanial activities and other activities. Being considered as advantaged scaffold, the alteration is made with different substituent. PMID:25692041

Biomolecules and Natural Medicine Preparations: Analysis of New Sources of Bioactive Compounds from Ribes and Rubus spp. Buds.

PubMed

Donno, Dario; Mellano, Maria Gabriella; Cerutti, Alessandro Kim; Beccaro, Gabriele Loris

2016-02-05

It is well known that plants are important sources for the preparation of natural remedies as they contain many biologically active compounds. In particular, polyphenols, terpenic compounds, organic acids, and vitamins are the most widely occurring groups of phytochemicals. Some endemic species may be used for the production of herbal preparations containing phytochemicals with significant bioactivity, as antioxidant activity and anti-inflammatory capacities, and health benefits. Blackberry sprouts and blackcurrant buds are known to contain appreciable levels of bioactive compounds, including flavonols, phenolic acids, monoterpenes, vitamin C, and catechins, with several clinical effects. The aim of this research was to perform an analytical study of blackcurrant and blackberry bud-preparations, in order to identify and quantify the main biomarkers, obtaining a specific phytochemical fingerprint to evaluate the single botanical class contribution to total phytocomplex and relative bioactivity, using a High Performance Liquid Chromatograph-Diode Array Detector; the same analyses were performed both on the University laboratory and commercial preparations. Different chromatographic methods were used to determine concentrations of biomolecules in the preparations, allowing for quantification of statistically significant differences in their bioactive compound content both in the case of Ribes nigrum and Rubus cultivated varieties at different harvest stages. In blackcurrant bud-extracts the most important class was organic acids (50.98%) followed by monoterpenes (14.05%), while in blackberry preparations the main bioactive classes were catechins (50.06%) and organic acids (27.34%). Chemical, pharmaceutical and agronomic-environmental knowledge could be important for obtaining label certifications for the valorization of specific genotypes, with high clinical and pharmaceutical value: this study allowed to develop an effective tool for the natural preparation quality control and bioactivity evaluation through the chemical fingerprinting of bud preparations.

Analysis of Pharmaceutical and Personal Care Compounds in Wastewater Sludge and Aqueous Samples using GC-MS/MS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhong, Lirong; Mitroshkov, Alexandre V.; Gilmore, Tyler J.

The Bioenergy Program at Pacific Northwest National Laboratory (PNNL) is evaluating the feasibility of converting wastewater sludge materials to fuels. Wastewater sludge from various municipalities will be used in the evaluation process and as with any municipal waste, there is the potential for residual contaminates to remain in the sludge following wastewater treatment. Many surveys and studies have confirmed the presence of pharmaceuticals in municipal wastewater and effluents (World Health Organization, 2011). Determination of the presence and concentrations of the contaminants is required to define the proper handling of this sludge. A list of targeted compounds was acquired from themore » literature and an analytical method was developed for the pharmaceutical and personal care compounds. The presence of organics complicated the analytical techniques and, in some cases, the precision of the results. However, residual concentrations of a range of compounds were detected in the wastewater sludge and the presence and concentrations of these compounds will be considered in identifying the appropriate handling of this material in conduct of research.« less

Antibiotic, Pharmaceutical, and Wastewater-Compound Data for Michigan, 1998-2005

USGS Publications Warehouse

Haack, Sheridan Kidd

2010-01-01

Beginning in the late 1990's, the U.S. Geological Survey began to develop analytical methods to detect, at concentrations less than 1 microgram per liter (ug/L), emerging water contaminants such as pharmaceuticals, personal-care chemicals, and a variety of other chemicals associated with various human and animal sources. During 1998-2005, the U.S. Geological Survey analyzed the following Michigan water samples: 41 samples for antibiotic compounds, 28 samples for pharmaceutical compounds, 46 unfiltered samples for wastewater compounds (dissolved and suspended compounds), and 113 filtered samples for wastewater compounds (dissolved constituents only). The purpose of this report is to summarize the status of emerging contaminants in Michigan waters based on data from several different project-specific sample-collection efforts in Michigan during an 8-year period. During the course of the 8-year sampling effort, antibiotics were determined at 20 surface-water sites and 2 groundwater sites, pharmaceuticals were determined at 11 surface-water sites, wastewater compounds in unfiltered water were determined at 31 surface-water sites, and wastewater compounds in filtered water were determined at 40 surface-water and 4 groundwater sites. Some sites were visited only once, but others were visited multiple times. A variety of quality-assurance samples also were collected. This report describes the analytical methods used, describes the variations in analytical methods and reporting levels during the 8-year period, and summarizes all data using current (2009) reporting criteria. Very few chemicals were detected at concentrations greater than current laboratory reporting levels, which currently vary from a low of 0.005 ug/L for some antibiotics to 5 ug/L for some wastewater compounds. Nevertheless, 10 of 51 chemicals in the antibiotics analysis, 9 of 14 chemicals in the pharmaceuticals analysis, 34 of 67 chemicals in the unfiltered-wastewater analysis, and 56 of 62 chemicals in the filtered-wastewater analysis were detected. Antibiotics were detected at 7 of 20 tested surface-water sites, but none were detected in 2 groundwater samples. Pharmaceuticals were detected at 7 of 11 surface-water sites. Wastewater compounds were detected at 25 of 31 sites for which unfiltered water samples were analyzed and at least once at all 40 surface-water sites and all 4 groundwater sites for which filtered water samples were analyzed. Overall, the chemicals detected most frequently in Michigan waters were similar to those reported frequently in other studies nationwide. Patterns of chemical detections were site specific and appear to be related to local sources, overall land use, and hydrologic conditions at the time of sampling. Field-blank results provide important information for the design of future sampling programs in Michigan and demonstrate the need for careful field-study design. Field-replicate results indicated substantial confidence regarding the presence or absence of the many chemicals tested. Overall, data reported herein indicate that a wide array of antibiotic, pharmaceutical, and organic wastewater compounds occur in Michigan waters. Patterns of occurrence, with respect to hydrologic, land use, and source variables, generally appear to be similar for Michigan as for other sampled waters across the United States. The data reported herein can serve as a basis for future studies in Michigan.

Case Report: Diabetic Foot Ulcer Infection Treated with Topical Compounded Medications.

PubMed

Agbi, Kelechi E; Carvalho, Maria; Phan, Ha; Tuma, Cristiane

2017-01-01

An adult diabetic male with three toes amputated on his right foot presented with an ulcer infection on his left foot, unresponsive to conventional antifungal oral medication for over two months. The ulcerated foot wound had a large impairment on the patient's quality of life, as determined by the Wound-QoL questionnaire. The compounding pharmacist recommended and the physician prescribed two topical compounded medicines, which were applied twice a day, free of charge at the compounding pharmacy. The foot ulcer infection was completely resolved following 13 days of treatment, with no longer any impairment on the patient's quality of life. This scientific case study highlights the value of pharmaceutical compounding in current therapeutics, the importance of the triad relationship, and the key role of the compounding pharmacist in diabetes care. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

[Mechanism of Tongsaimai tablet for atherosclerosis based on network pharmacology].

PubMed

Li, Na; Zhang, Xin-Zhuang; Wang, Yan-Ru; Cao, Liang; Ding, Gang; Wang, Zhen-Zhong; Xiao, Wei; Xu, Xiao-Jie

2016-05-01

Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Tongsaimai tablets for atherosclerosis. In molecular docking and molecular-target protein network analysis, 97 molecules in Tongsaimai tablets showed good interaction with the atherosclerosis-related target protein (docking score ≥ 7), and 37 molecules of them could act on more than 2 targets (≥ 2) with higher betweenness, suggesting that these 37 molecules might be the main active compounds group in Tongsaimai tablets for atherosclerosis treatment. Furthermore, the predicted active compounds contained more flavonoids and saponins, reminding more attention should be paid on flavonoids and saponins in study of effective compounds and quality standards of Tongsaimai tablets. Targets network analysis showed that, the active compounds of Tongsaimai tablets could regulate inflammation, stabilize plaque, protect vascular endothelial cell, regulate blood lipid and inhibit blood coagulation through acting on the main 22 target proteins, such as Toll-like receptors (TLR1, TLR2), matrix metalloproteinase (MMP1, MMP2, MMP3, MMP9), angiotensin converting enzyme (ACE), leukotriene A4 hydrolase (LTA4-H), 5-lipoxidase (5-LOX), peroxisome proliferators-activated receptors (PPARα, PPARγ). These active compounds can participate in regulating different pathologic stages of atherosclerosis and thus treat atherosclerosis finally. This study revealed the main active compounds and possible mechanism of Tongsaimai tablets for treatment of atherosclerosis and meanwhile, verified the characteristics of multi-components, multi-targets and integral regulation for Tongsaimai tablets, providing theoretical references for the following systematic laboratory experiments on effective compounds and action mechanism of Tongsaimai Tablet. Copyright© by the Chinese Pharmaceutical Association.

Compounds affecting cholesterol absorption

NASA Technical Reports Server (NTRS)

Koo, Sung I. (Inventor); Noh, Sang K. (Inventor); Hua, Duy H. (Inventor)

2004-01-01

A class of novel compounds is described for use in affecting lymphatic absorption of cholesterol. Compounds of particular interest are defined by Formula I: ##STR1## or a pharmaceutically acceptable salt thereof.

Chemical Variability and Biological Activities of Eucalyptus spp. Essential Oils.

PubMed

Barbosa, Luiz Claudio Almeida; Filomeno, Claudinei Andrade; Teixeira, Robson Ricardo

2016-12-07

Many plant species produce mixtures of odorous and volatile compounds known as essential oils (EOs). These mixtures play important roles in Nature and have been utilized by mankind for different purposes, such as pharmaceuticals, agrochemicals, aromatherapy, and food flavorants. There are more than 3000 EOs reported in the literature, with approximately 300 in commercial use, including the EOs from Eucalyptus species. Most EOs from Eucalyptus species are rich in monoterpenes and many have found applications in pharmaceuticals, agrochemicals, food flavorants, and perfumes. Such applications are related to their diverse biological and organoleptic properties. In this study, we review the latest information concerning the chemical composition and biological activities of EOs from different species of Eucalyptus . Among the 900 species and subspecies of the Eucalyptus genus, we examined 68 species. The studies associated with these species were conducted in 27 countries. We have focused on the antimicrobial, acaricidal, insecticidal and herbicidal activities, hoping that such information will contribute to the development of research in this field. It is also intended that the information described in this study can be useful in the rationalization of the use of Eucalyptus EOs as components for pharmaceutical and agrochemical applications as well as food preservatives and flavorants.

Environmental exposure modeling and monitoring of human pharmaceutical concentrations in the environment

USGS Publications Warehouse

Versteeg, D.J.; Alder, A. C.; Cunningham, V. L.; Kolpin, D.W.; Murray-Smith, R.; Ternes, T.

2005-01-01

Human pharmaceuticals are receiving increased attention as environmental contaminants. This is due to their biological activity and the number of monitoring programs focusing on analysis of these compounds in various environmental media and compartments. Risk assessments are needed to understand the implications of reported concentrations; a fundamental part of the risk assessment is an assessment of environmental exposures. The purpose of this chapter is to provide guidance on the use of predictive tools (e.g., models) and monitoring data in exposure assessments for pharmaceuticals in the environment. Methods to predict environmental concentrations from equations based on first principles are presented. These equations form the basis of existing GIS (geographic information systems)-based systems for understanding the spatial distribution of pharmaceuticals in the environment. The pharmaceutical assessment and transport (PhATE), georeferenced regional exposure assessment tool for European rivers (GREAT-ER), and geographical information system (GIS)-ROUT models are reviewed and recommendations are provided concerning the design and execution of monitoring studies. Model predictions and monitoring data are compared to evaluate the relative utility of each approach in environmental exposure assessments. In summary, both models and monitoring data can be used to define representative exposure concentrations of pharmaceuticals in the environment in support of environmental risk assessments.

Assessment of the antioxidant and antibacterial activities of different olive processing wastewaters

PubMed Central

Tan, Shiau Pin; El-Abbassi, Abdelilah; Kiai, Hajar; Hafidi, Abdellatif; O’Donovan, Orla; McLoughlin, Peter

2017-01-01

Olive processing wastewaters (OPW), namely olive mill wastewater (OMW) and table-olive wastewaters (TOW) were evaluated for their antibacterial activity against five Gram-positive and two Gram-negative bacteria using the standard disc diffusion and thin layer chromatography (TLC)-bioautography assays. Disc diffusion screening and bioautography of OMW were compared to the phenolic extracts of table-olive brines. Positive activity against S. aureus was demonstrated. The optimization of chromatographic separation revealed that hexane/acetone in the ratio of 4:6 was the most effective for phenolic compounds separation. A HPLC-MS analysis was performed showing that only two compounds, hydroxytyrosol and tyrosol, were the predominant phenolic compounds in all OPW. The phenolic extract of OMW generated by a semi-modern process showed the highest free radical-scavenging activity (DPPH assay) compared to the other phenolic extracts. It is apparent from the present study that OPW are a rich source of antioxidants suitable for use in food, cosmetic or pharmaceutical applications. PMID:28873097

Overview on the Biochemical Potential of Filamentous Fungi to Degrade Pharmaceutical Compounds

PubMed Central

Olicón-Hernández, Darío R.; González-López, Jesús; Aranda, Elisabet

2017-01-01

Pharmaceuticals represent an immense business with increased demand due to intensive livestock raising and an aging human population, which guarantee the quality of human life and well-being. However, the development of removal technologies for these compounds is not keeping pace with the swift increase in their use. Pharmaceuticals constitute a potential risk group of multiclass chemicals of increasing concern since they are extremely frequent in all environments and have started to exhibit negative effects on micro- and macro-fauna as well as on human health. In this context, fungi are known to be extremely diverse and poorly studied microorganisms despite being well suited for bioremediation processes, taking into account their metabolic and physiological characteristics for the transformation of even highly toxic xenobiotic compounds. Increasing studies indicate that fungi can transform many structures of pharmaceutical compounds, including anti-inflammatories, β-blockers, and antibiotics. This is possible due to different mechanisms in combination with the extracellular and intracellular enzymes, which have broad of biotechnological applications. Thus, fungi and their enzymes could represent a promising tool to deal with this environmental problem. Here, we review the studies performed on pharmaceutical compounds biodegradation by the great diversity of these eukaryotes. We examine the state of the art of the current application of the Basidiomycota division, best known in this field, as well as the assembly of novel biodegradation pathways within the Ascomycota division and the Mucoromycotina subdivision from the standpoint of shared enzymatic systems, particularly for the cytochrome P450 superfamily of enzymes, which appear to be the key enzymes in these catabolic processes. Finally, we discuss the latest advances in the field of genetic engineering for their further application. PMID:28979245

Inhibitors of 7-Dehydrocholesterol Reductase: Screening of a Collection of Pharmacologically Active Compounds in Neuro2a Cells.

PubMed

Kim, Hye-Young H; Korade, Zeljka; Tallman, Keri A; Liu, Wei; Weaver, C David; Mirnics, Karoly; Porter, Ned A

2016-05-16

A small library of pharmacologically active compounds (the NIH Clinical Collection) was assayed in Neuro2a cells to determine their effect on the last step in the biosynthesis of cholesterol, the transformation of 7-dehydrocholesterol (7-DHC) to cholesterol promoted by 7-dehydrocholesterol reductase, DHCR7. Of some 727 compounds in the NIH Clinical Collection, over 30 compounds significantly increased 7-DHC in Neuro2a cells when assayed at 1 μM. Active compounds that increased 7-DHC with a Z-score of +3 or greater generally gave rise to modest decreases in desmosterol and increases in lanosterol levels. Among the most active compounds identified in the library were the antipsychotic, antidepressant, and anxiolytic compounds that included perospirone, nefazodone, haloperidol, aripiprazole, trazodone, and buspirone. Fluoxetine and risperidone were also active at 1 μM, and another 10 compounds in this class of pharmaceuticals were identified in the screen at concentrations of 10 μM. Increased levels of 7-DHC are associated with Smith-Lemli-Opitz syndrome (SLOS), a human condition that results from a mutation in the gene that encodes DHCR7. The SLOS phenotype includes neurological deficits and congenital malformations, and it is linked to a higher incidence of autism spectrum disorder. The significance of the current study is that it identifies common pharmacological compounds that may induce a biochemical presentation similar to SLOS. Little is known about the side effects of elevated 7-DHC postdevelopmentally, and the elevated 7-DHC that results from exposure to these compounds may also be a confounder in the diagnosis of SLOS.

Predicting concentrations of trace organic compounds in municipal wastewater treatment plant sludge and biosolids using the PhATE™ model.

PubMed

Cunningham, Virginia L; D'Aco, Vincent J; Pfeiffer, Danielle; Anderson, Paul D; Buzby, Mary E; Hannah, Robert E; Jahnke, James; Parke, Neil J

2012-07-01

This article presents the capability expansion of the PhATE™ (pharmaceutical assessment and transport evaluation) model to predict concentrations of trace organics in sludges and biosolids from municipal wastewater treatment plants (WWTPs). PhATE was originally developed as an empirical model to estimate potential concentrations of active pharmaceutical ingredients (APIs) in US surface and drinking waters that could result from patient use of medicines. However, many compounds, including pharmaceuticals, are not completely transformed in WWTPs and remain in biosolids that may be applied to land as a soil amendment. This practice leads to concerns about potential exposures of people who may come into contact with amended soils and also about potential effects to plants and animals living in or contacting such soils. The model estimates the mass of API in WWTP influent based on the population served, the API per capita use, and the potential loss of the compound associated with human use (e.g., metabolism). The mass of API on the treated biosolids is then estimated based on partitioning to primary and secondary solids, potential loss due to biodegradation in secondary treatment (e.g., activated sludge), and potential loss during sludge treatment (e.g., aerobic digestion, anaerobic digestion, composting). Simulations using 2 surrogate compounds show that predicted environmental concentrations (PECs) generated by PhATE are in very good agreement with measured concentrations, i.e., well within 1 order of magnitude. Model simulations were then carried out for 18 APIs representing a broad range of chemical and use characteristics. These simulations yielded 4 categories of results: 1) PECs are in good agreement with measured data for 9 compounds with high analytical detection frequencies, 2) PECs are greater than measured data for 3 compounds with high analytical detection frequencies, possibly as a result of as yet unidentified depletion mechanisms, 3) PECs are less than analytical reporting limits for 5 compounds with low analytical detection frequencies, and 4) the PEC is greater than the analytical method reporting limit for 1 compound with a low analytical detection frequency, possibly again as a result of insufficient depletion data. Overall, these results demonstrate that PhATE has the potential to be a very useful tool in the evaluation of APIs in biosolids. Possible applications include: prioritizing APIs for assessment even in the absence of analytical methods; evaluating sludge processing scenarios to explore potential mitigation approaches; using in risk assessments; and developing realistic nationwide concentrations, because PECs can be represented as a cumulative probability distribution. Finally, comparison of PECs to measured concentrations can also be used to identify the need for fate studies of compounds of interest in biosolids. Copyright © 2011 SETAC.

Chiral pharmaceuticals: A review on their environmental occurrence and fate processes.

PubMed

Sanganyado, Edmond; Lu, Zhijiang; Fu, Qiuguo; Schlenk, Daniel; Gan, Jay

2017-11-01

More than 50% of pharmaceuticals in current use are chiral compounds. Enantiomers of the same pharmaceutical have identical physicochemical properties, but may exhibit differences in pharmacokinetics, pharmacodynamics and toxicity. The advancement in separation and detection methods has made it possible to analyze trace amounts of chiral compounds in environmental media. As a result, interest on chiral analysis and evaluation of stereoselectivity in environmental occurrence, phase distribution and degradation of chiral pharmaceuticals has grown substantially in recent years. Here we review recent studies on the analysis, occurrence, and fate of chiral pharmaceuticals in engineered and natural environments. Monitoring studies have shown ubiquitous presence of chiral pharmaceuticals in wastewater, surface waters, sediments, and sludge, particularly β-receptor antagonists, analgesics, antifungals, and antidepressants. Selective sorption and microbial degradation have been demonstrated to result in enrichment of one enantiomer over the other. The changes in enantiomer composition may also be caused by biologically catalyzed chiral inversion. However, accurate evaluation of chiral pharmaceuticals as trace environmental pollutants is often hampered by the lack of identification of the stereoconfiguration of enantiomers. Furthermore, a systematic approach including occurrence, fate and transport in various environmental matrices is needed to minimize uncertainties in risk assessment of chiral pharmaceuticals as emerging environmental contaminants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of pharmaceutical cocrystals: the effects on drug pharmacokinetics.

PubMed

Shan, Ning; Perry, Miranda L; Weyna, David R; Zaworotko, Michael J

2014-09-01

Pharmaceutical cocrystallization has emerged in the past decade as a new strategy to enhance the clinical performance of orally administered drugs. A pharmaceutical cocrystal is a multi-component crystalline material in which the active pharmaceutical ingredient is in a stoichiometric ratio with a second compound that is generally a solid under ambient conditions. The resulting cocrystal exhibits different solid-state thermodynamics, leading to changes in physicochemical properties that offer the potential to significantly modify drug pharmacokinetics. The impact of cocrystallization upon drug pharmacokinetics has not yet been well delineated. Herein, we compile previously published data to address two salient questions: what effect does cocrystallization impart upon physicochemical properties of a drug substance and to what degree can those effects impact its pharmacokinetics. Cocrystals can impact various aspects of drug pharmacokinetics, including, but not limited to, drug absorption. The diversity of solid forms offered through cocrystallization can facilitate drastic changes in solubility and pharmacokinetics. Therefore, it is unsurprising that cocrystal screening is now a routine step in early-stage drug development. With the increasing recognition of pharmaceutical cocrystals from clinical, regulatory and legal perspectives, the systematic commercialization of cocrystal containing drug products is just a matter of time.

The application of structure-based assessment to support safety and chemistry diligence to manage genotoxic impurities in active pharmaceutical ingredients during drug development.

PubMed

Dobo, Krista L; Greene, Nigel; Cyr, Michelle O; Caron, Stéphane; Ku, Warren W

2006-04-01

Starting materials and intermediates used to synthesize pharmaceuticals are reactive in nature and may be present as impurities in the active pharmaceutical ingredient (API) used for preclinical safety studies and clinical trials. Furthermore, starting materials and intermediates may be known or suspected mutagens and/or carcinogens. Therefore, during drug development due diligence need be applied from two perspectives (1) to understand potential mutagenic and carcinogenic risks associated with compounds used for synthesis and (2) to understand the capability of synthetic processes to control genotoxic impurities in the API. Recently, a task force comprised of experts from pharmaceutical industry proposed guidance, with recommendations for classification, testing, qualification and assessing risk of genotoxic impurities. In our experience the proposed structure-based classification, has differentiated 75% of starting materials and intermediates as mutagenic and non-mutagenic with high concordance (92%) when compared with Ames results. Structure-based assessment has been used to identify genotoxic hazards, and prompted evaluation of fate of genotoxic impurities in API. These two assessments (safety and chemistry) culminate in identification of genotoxic impurities known or suspected to exceed acceptable levels in API, thereby triggering actions needed to assure appropriate control and measurement methods are in place. Hypothetical case studies are presented demonstrating this multi-disciplinary approach.

3-Bromopyruvate as a potential pharmaceutical in the light of experimental data.

PubMed

Szczuka, Izabela; Gamian, Andrzej; Terlecki, Grzegorz

2017-12-08

3-Bromopyruvate (3-BrPA) is an halogenated analogue of pyruvic acid known for over four decades as an alkylating agent reacting with thiol groups of many proteins. It enters animal cells like a lactate: via monocarboxylic acid transporters. Increasing interest in this compound, in recent times, is mainly due to hopes associated with its anticancer action. It is based on the impairment of energy metabolism of tumor cells by inhibiting enzymes in the glycolysis pathway (hexokinase II, glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase) and the oxidative phosphorylation (succinate dehydrogenase). Two cases of clinical application of this compound in the treatment of advanced cancers were reported. By using 3-BrPA, rheumatoid arthritis in SKG mice has been reduced. This compound has also antiparasitic activity: lowers cell viability of Trypanosoma brucei, decreases intracellular proliferation of Toxoplasma gondii and reduces the metabolic activity of Schistosoma mansoni. It also has antifungal properties; particularly it acts strongly on Cryptococcus neoformans, as well as Saccharomyces cerevisiae. An inhibitory effect on bacterial enzymes was also described on: isocitrate lyase from Escherichia coli, Mycobacterium tuberculosis, Pseudomonas indigofera and 2-methylisocitrate lyase, succinate dehydrogenase and acetohydroxylic acid synthase from Escherichia coli. Wherever undesirable (cancer, parasitic) cells differ from normal by more intense glycolysis and higher energy needs, there is a good chance of successful 3-BrPA use. However, this compound acts on all cells and it, therefore, seems that its future as a pharmaceutical is dependent upon the development of appropriate methods for its effective and safe application.

Ecotoxicity and environmental risk assessment of pharmaceuticals and personal care products in aquatic environments and wastewater treatment plants.

PubMed

Ortiz de García, Sheyla Andrea; Pinto Pinto, Gilberto; García-Encina, Pedro A; Irusta-Mata, Rubén

2014-10-01

A wide range of pharmaceuticals and personal care products (PPCPs) are present in the environment, and many of their adverse effects are unknown. The environmental risk assessment of 26 PPCPs of relevant consumption and occurrence in the aquatic environment in Spain was accomplished in this research. Based on the ecotoxicity values obtained by bioluminescence and respirometry assays and by predictions using the US EPA ecological structure-activity relationship (ECOSAR™), the compounds were classified following the Globally Harmonized System of Classification and Labelling of Chemicals. According to the criteria of the European Medicines Agency, the real risk of impact of these compounds in wastewater treatment plants (WWTPs) and in the aquatic environment was predicted. In at least two ecotoxicity tests, 65.4 % of the PPCPs under study showed high toxicity or were harmful to aquatic organisms. The global order of the species' sensitivity to the PPCPs considered was as follows: Vibrio fischeri (5 min) > Vibrio fischeri (15 min) > algae > crustaceans > fish > biomass of WWTP. Acetaminophen, ciprofloxacin, clarithromycin, clofibrate, ibuprofen, omeprazole, triclosan, parabens and 1,4-benzoquinone showed some type of risk for the aquatic environments and/or for the activated sludge of WWTPs. Development of acute and chronic ecotoxicity data, the determination of predicted and measured environmental concentrations of PPCPs, the inclusion of metabolites and transformation products and the evaluation of mixtures of these compounds will allow further improvements of the results of the ERAs and, finally, to efficiently identify the compounds that could affect the environment.

An empirical analysis of primary and secondary pharmaceutical patents in Chile.

PubMed

Abud, María José; Hall, Bronwyn; Helmers, Christian

2015-01-01

We analyze the patent filing strategies of foreign pharmaceutical companies in Chile distinguishing between "primary" (active ingredient) and "secondary" patents (patents on modified compounds, formulations, dosages, particular medical uses, etc.). There is prior evidence that secondary patents are used by pharmaceutical originator companies in the U.S. and Europe to extend patent protection on drugs in length and breadth. Using a novel dataset that comprises all drugs registered in Chile between 1991 and 2010 as well as the corresponding patents and trademarks, we find evidence that foreign originator companies pursue similar strategies in Chile. We find a primary to secondary patents ratio of 1:4 at the drug-level, which is comparable to the available evidence for Europe; most secondary patents are filed over several years following the original primary patent and after the protected active ingredient has obtained market approval in Chile. This points toward effective patent term extensions through secondary patents. Secondary patents dominate "older" therapeutic classes like anti-ulcer and anti-depressants. In contrast, newer areas like anti-virals and anti-neoplastics (anti-cancer) have a much larger share of primary patents.

Sorption of paracetamol onto biomaterials.

PubMed

Ferchichi, Maroua; Dhaouadi, Hatem

2016-01-01

Pharmaceutical residues released into the environment are posing more and more public health problems. It is worthwhile to study the retention of pharmaceuticals residues by adsorption on solid supports. Batch sorption experiments are intended to identify the adsorption isotherms of the pharmaceutically active ingredient on the biomaterials. The results obtained in this study have shown that the retention possibilities of these compounds by bio-adsorbents (clay and sand) are not significant. The negligible sorption for these media is explained by the low hydrophobicity of paracetamol (Log K(ow) = 0.46). The retention of paracetamol on the dehydrated sewage sludge and on Posidonia oceanica showed a relatively significant adsorption with a maximal quantity of 0.956 mg g(-1) and 1.638 mg g(-1) for the dehydrate sludge and P. oceanica, respectively. On the other hand, the study of paracetamol retention on the powdered activated carbon showed a high adsorption capacity of about 515.27 mg g(-1). Isotherm data show a good fit with Langmuir's model. An infrared analysis is carried out. It shows identical bands before and after adsorption, with some modifications.

Effect of ultrasonic and ozone pre-treatments on pharmaceutical waste activated sludge's solubilisation, reduction, anaerobic biodegradability and acute biological toxicity.

PubMed

Pei, Jin; Yao, Hong; Wang, Hui; Shan, Dan; Jiang, Yichen; Ma, Lanqianya; Yu, Xiaohua

2015-09-01

Ultrasonic and ozone pre-treatment technologies were employed in this study to improve the anaerobic digestion efficiency of pharmaceutical waste activated sludge. The sludge solubilisation achieved 30.01% (150,000 kJ/kg TS) and 28.10% (0.1g O3/g TS) after ultrasonic treatment and ozone treatment. The anaerobic biodegradability after ultrasonic treatment was higher compared to ozonation due to the higher cumulative methane volume observed after 6 days (249 ml vs 190 ml). The ozonated sludge released the highest concentration of Cu(2+) into the liquid phase (6.640 mg L(-1)) compared to 0.530 mg/L for untreated sludge and 0.991 mg/L for sonicated sludge. The acute toxicity test measured by luminescent bacteria showed that anaerobic digestion could degrade toxic compounds and result in a reduction in toxicity. The main mechanism of action led to some differences in the treated sludge exhibiting higher potential for methane production from pharmaceutical waste sludge with ultrasonic treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Significance of Lichens and Their Metabolites

NASA Astrophysics Data System (ADS)

Huneck, S.

Lichens, symbiontic organisms of fungi and algae, synthesize numerous metabolites, the "lichen substances," which comprise aliphatic, cycloaliphatic, aromatic, and terpenic compounds. Lichens and their metabolites have a manifold biological activity: antiviral, antibiotic, antitumor, allergenic, plant growth inhibitory, antiherbivore, and enzyme inhibitory. Usnic acid, a very active lichen substance is used in pharmaceutical preparations. Large amounts of Pseudevernia furfuracea and Evernia prunastri are processed in the perfume industry, and some lichens are sensitive reagents for the evaluation of air pollution.

Pharmaceuticals in biota in the aquatic environment: analytical methods and environmental implications.

PubMed

Huerta, B; Rodríguez-Mozaz, S; Barceló, D

2012-11-01

The presence of pharmaceuticals in the aquatic environment is an ever-increasing issue of concern as they are specifically designed to target specific metabolic and molecular pathways in organisms, and they may have the potential for unintended effects on nontarget species. Information on the presence of pharmaceuticals in biota is still scarce, but the scientific literature on the subject has established the possibility of bioaccumulation in exposed aquatic organisms through other environmental compartments. However, few studies have correlated both bioaccumulation of pharmaceutical compounds and the consequent effects. Analytical methodology to detect pharmaceuticals at trace quantities in biota has advanced significantly in the last few years. Nonetheless, there are still unresolved analytical challenges associated with the complexity of biological matrices, which require exhaustive extraction and purification steps, and highly sensitive and selective detection techniques. This review presents the trends in the analysis of pharmaceuticals in aquatic organisms in the last decade, recent data about the occurrence of these compounds in natural biota, and the environmental implications that chronic exposure could have on aquatic wildlife.

Characterization of extractives in durable and non-durable hardwoods: Black locust, Catalpa, and Honey mesquite

Treesearch

Roderquita K. Moore; Doreen Mann; Gabriel Epstein; Phoebe Wagner; Brett Hinkforth; Jun Hyunji

2017-01-01

Hardwoods are a class of tree that holds multiple types of extractives, some of which have their own specialized biological activity. Characterizing these compounds in greater depth can help virologists understand how natural chemicals are able to resist infection, leading to pharmaceutical uses. Hardwoods are known to contain high concentrations of different phenolic...

Uptake and effects of a mixture of widely used therapeutic drugs in Eruca sativa L. and Zea mays L. plants.

PubMed

Marsoni, Milena; De Mattia, Fabrizio; Labra, Massimo; Bruno, Antonia; Bracale, Marcella; Vannini, Candida

2014-10-01

Pharmaceutically active compounds (PACs) are continuously dispersed into the environment due to human and veterinary use, giving rise to their potential accumulation in edible plants. In this study, Eruca sativa L. and Zea mays L. were selected to determine the potential uptake and accumulation of eight different PACs (Salbutamol, Atenolol, Lincomycin, Cyclophosphamide, Carbamazepine, Bezafibrate, Ofloxacin and Ranitidine) designed for human use. To mimic environmental conditions, the plants were grown in pots and irrigated with water spiked with a mixture of PACs at concentrations found in Italian wastewaters and rivers. Moreover, 10× and 100× concentrations of these pharmaceuticals were also tested. The presence of the pharmaceuticals was tested in the edible parts of the plants, namely leaves for E. sativa and grains for Z. mays. Quantification was performed by liquid chromatography mass spectroscopy (LC/MS/MS). In the grains of 100× treated Z. mays, only atenolol, lincomycin and carbamazepine were above the limit of detection (LOD). At the same concentration in E. sativa plants the uptake of all PACs was >LOD. Lincomycin and oflaxacin were above the limit of quantitation in all conditions tested in E. sativa. The results suggest that uptake of some pharmaceuticals from the soil may indeed be a potential transport route to plants and that these environmental pollutants can reach different edible parts of the selected crops. Measurements of the concentrations of these pharmaceuticals in plant materials were used to model potential adult human exposure to these compounds. The results indicate that under the current experimental conditions, crops exposed to the selected pharmaceutical mixture would not have any negative effects on human health. Moreover, no significant differences in the growth of E. sativa or Z. mays plants irrigated with PAC-spiked vs. non-spiked water were observed. Copyright © 2014 Elsevier Inc. All rights reserved.

A fruitful decade from 2005 to 2014 for anthraquinone patents.

PubMed

Hussain, Hidayat; Al-Harrasi, Ahmed; Al-Rawahi, Ahmed; Green, Ivan R; Csuk, René; Ahmed, Ishtiaq; Shah, Afzah; Abbas, Ghulam; Rehman, Najeeb Ur; Ullah, Riaz

2015-01-01

Anthraquinones are aromatic compounds whose structures are related to anthracene (parent structure: 9,10-dioxoanthracene) for which various methods for their synthesis have been developed. In the past decade (2005 - 2014), much work has been done regarding anthraquinone chemistry in order to discover new compounds related to this scaffold as anticancer, antibacterial, antidiabetic, antiviral, anti-HCV, antifibrotic, fungicidal and anti-inflammatory agents. This review covers the patents on therapeutic activities of anthraquinones and their derivatives in the years between 2005 and 2014. A large portion of the therapeutic applications that were reported in international patents will be presented and discussed. Although a large number of patents have been registered over the last decade, this review is focused on important patents related to cancer, inflammation, infectious diseases, diabetic conditions and hepatitis C. The tricyclic planar ring system of anthraquinones displays a wide range of important pharmaceutical properties. By linking active anthraquinone analogs to other important pharmacophores or conjugates such as oximes, N-heterocycles, benzodiazepines or glycosyl ethers, their anticancer potential is enhanced. The ability of anthraquinone analogs to become more prominent as novel pharmaceutical agents may further be enhanced by fusing functionalized heterocyclic rings onto established anthraquinone cores.

Ethnopharmacological uses, phytochemistry, biological activities, and biotechnological applications of Eclipta prostrata.

PubMed

Chung, Ill-Min; Rajakumar, Govindasamy; Lee, Ji-Hee; Kim, Seung-Hyun; Thiruvengadam, Muthu

2017-07-01

Eclipta prostrata belongs to a family of medicinal plants (Asteraceae) and plays a role in the treatment of several diseases, including infectious hepatitis, snake venom poisoning, gastritis, and respiratory diseases such as a cough and asthma. A number of compounds, including thiophene derivatives, steroids, triterpenes, flavonoids, polyacetylenes, polypeptides, and coumestans, have been isolated from E. prostrata. The plant functional compounds can act as reducing agent in the field of nanoparticle synthesis. The extracts of E. prostrata are widely used for green biosynthesis of various metal and metal oxide nanoparticles, nanoparticles, which showed a potential for pharmaceutical, biotechnological, and biomedical applications. Establishment of a efficient in vitro regeneration and genetic transformation method of E. prostrata is a vital prerequisite for application of biotechnology in order to improve secondary metabolite yields. The present mini-review discusses its pharmacological profile, chemical constituents, biotechnological, and ethnomedical uses, mainly focusing on antimyotoxic, antihemorrhagic, antiproliferative, antioxidant, antitumor, antihyperglycemic, antidementia, antimicrobial, antihyperlipidemic, antivenom, anti-HIV, and larvicidal activities, so that the pharmaceutical potential of the plant can be better evaluated. The mini review, providing up-to-date phytochemical and other information on E. prostrata, will serve a reference for further studies.

The Joint European Compound Library: boosting precompetitive research.

PubMed

Besnard, Jérémy; Jones, Philip S; Hopkins, Andrew L; Pannifer, Andrew D

2015-02-01

The Joint European Compound Library (JECL) is a new high-throughput screening collection aimed at driving precompetitive drug discovery and target validation. The JECL has been established with a core of over 321,000 compounds from the proprietary collections of seven pharmaceutical companies and will expand to around 500,000 compounds. Here, we analyse the physicochemical profile and chemical diversity of the core collection, showing that the collection is diverse and has a broad spectrum of predicted biological activity. We also describe a model for sharing compound information from multiple proprietary collections, enabling diversity and quality analysis without disclosing structures. The JECL is available for screening at no cost to European academic laboratories and SMEs through the IMI European Lead Factory (http://www.europeanleadfactory.eu/). Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Basics of Compounding: 3D Printing--Pharmacy Applications, Part 2.

PubMed

Allen, Loyd V

2017-01-01

3D printing is a standard tool in the automotive, aerospace, and consumer goods in industry and is gaining traction in pharmaceutical manufacturing, which has introduced a new element into dosage-form development. This article, which represents part 2 of a 3-part article on the topic of 3D printing, discusses the different technologies available for 3D printing. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds.

PubMed

Loh, Yong Yao; Nagao, Kazunori; Hoover, Andrew J; Hesk, David; Rivera, Nelo R; Colletti, Steven L; Davies, Ian W; MacMillan, David W C

2017-12-01

Deuterium- and tritium-labeled pharmaceutical compounds are pivotal diagnostic tools in drug discovery research, providing vital information about the biological fate of drugs and drug metabolites. Herein we demonstrate that a photoredox-mediated hydrogen atom transfer protocol can efficiently and selectively install deuterium (D) and tritium (T) at α-amino sp 3 carbon-hydrogen bonds in a single step, using isotopically labeled water (D 2 O or T 2 O) as the source of hydrogen isotope. In this context, we also report a convenient synthesis of T 2 O from T 2 , providing access to high-specific-activity T 2 O. This protocol has been successfully applied to the high incorporation of deuterium and tritium in 18 drug molecules, which meet the requirements for use in ligand-binding assays and absorption, distribution, metabolism, and excretion studies. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Exploring the gyrase ATPase domain for tailoring newer anti-tubercular drugs: hit to lead optimization of a novel class of thiazole inhibitors.

PubMed

Jeankumar, Variam Ullas; Kotagiri, Sonali; Janupally, Renuka; Suryadevara, Priyanka; Sridevi, Jonnalagadda Padma; Medishetti, Raghavender; Kulkarni, Pushkar; Yogeeswari, Perumal; Sriram, Dharmarajan

2015-02-01

Gyrase ATPase domain, the pharmaceutical underexploited segment of DNA gyrase, the sole Type II topoisomerase present in Mycobacterium tuberculosis represents an attractive target for anti-tubercular drug discovery. Here we report, the development of a novel series of MTB DNA gyraseB inhibitor identified through a medium throughput screening (MTS) of BITS in-house chemical library (3000 compounds). The MTS hit was further remodeled by chemical synthesis to identify the most potent analogue 27 exhibiting an in vitro gyrB inhibitory IC50 of 0.15 μM. The series also demonstrated well correlating gyrase super coiling activity and in vitro anti-mycobacterial potency against MTB H37Rv strain. Furthermore the compounds displayed good safety profile in their subsequent cytotoxicity and hERG toxicity evaluations, to be worked out from a pharmaceutical point of view as potential anti-tubercular agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

A novel approach to the discovery of anti-tumor pharmaceuticals: searching for activators of liponecrosis

PubMed Central

Arlia-Ciommo, Anthony; Svistkova, Veronika; Mohtashami, Sadaf; Titorenko, Vladimir I.

2016-01-01

A recently conducted chemical genetic screen for pharmaceuticals that can extend longevity of the yeast Saccharomyces cerevisiae has identified lithocholic acid as a potent anti-aging molecule. It was found that this hydrophobic bile acid is also a selective anti-tumor chemical compound; it kills different types of cultured cancer cells if used at concentrations that do not compromise the viability of non-cancerous cells. These studies have revealed that yeast can be successfully used as a model organism for high-throughput screens aimed at the discovery of selectively acting anti-tumor small molecules. Two metabolic traits of rapidly proliferating fermenting yeast, namely aerobic glycolysis and lipogenesis, are known to be similar to those of cancer cells. The mechanisms underlying these key metabolic features of cancer cells and fermenting yeast have been established; such mechanisms are discussed in this review. We also suggest how a yeast-based chemical genetic screen can be used for the high-throughput development of selective anti-tumor pharmaceuticals that kill only cancer cells. This screen consists of searching for chemical compounds capable of increasing the abundance of membrane lipids enriched in unsaturated fatty acids that would therefore be toxic only to rapidly proliferating cells, such as cancer cells and fermenting yeast. PMID:26636650

An insect-tapeworm model as a proxy for anthelminthic effects in the mammalian host.

PubMed

Woolsey, Ian David; Fredensborg, Brian L; Jensen, Per M; Kapel, Christian M O; Meyling, Nicolai V

2015-07-01

Invertebrate models provide several important advantages over their vertebrate counterparts including fewer legislative stipulations and faster, more cost-effective experimental procedures. Furthermore, various similarities between insect and mammalian systems have been highlighted. To obtain maximum use of invertebrate models in pharmacology, their fidelity as analogues of vertebrate systems requires verification. We utilised a flour beetle (Tenebrio molitor)-tapeworm (Hymenolepis diminuta) model to evaluate the efficacy of known anthelmintic compounds, praziquantel, mebendazole and levamisole against H. diminuta cysticercoid larvae in vitro. Inhibition of cysticercoid activity during the excystation procedure was used as a proxy for worm removal. The effects of the three compounds mirrored their relative efficacy in treatment against adult worms in mammalian systems; however, further study is required to determine the fidelity of this model in relation to dose administered. The model precludes comparison of consecutive daily administration of pharmaceuticals in mammals due to cysticercoids not surviving outside of the host for multiple days. Treatment of beetles in vivo, followed by excystation of cysticercoids postdissection could potentially allow for such comparisons. Further model validation will include analysis of pharmaceutical efficacy in varying H. diminuta isolates and pharmaceutical dilution in solvents other than water. Notwithstanding, our results demonstrate that this model holds promise as a method to efficiently identify promising new cestocidal candidates.

Solubility of pharmaceuticals: A comparison between SciPharma, a PC-SAFT-based approach, and NRTL-SAC

NASA Astrophysics Data System (ADS)

Bouillot, Baptiste; Spyriouni, Theodora; Teychené, Sébastien; Biscans, Béatrice

2017-04-01

The solubility of seven pharmaceutical compounds (paracetamol, benzoic acid, 4-aminobenzoic acid, salicylic acid, ibuprofen, naproxen and temazepam) in pure and mixed solvents as a function of temperature is calculated with SciPharma, a semi-empirical approach based on PC-SAFT, and the NRTL-SAC model. To conduct a fair comparison between the approaches, the parameters of the compounds were regressed against the same solubility data, chosen to account for hydrophilic, polar and hydrophobic interactions. Only these solubility data were used by both models for predicting solubility in other pure and mixed solvents for which experimental data were available for comparison. A total of 386 pure solvent data points were used for the comparison comprising one or more temperatures per solvent. SciPharma is found to be more accurate than NRTL-SAC on the pure solvent data used especially in the description of the temperature dependence. This is due to the appropriate parameterization of the pharmaceuticals and the temperature-dependent description of the activity coefficient in PC-SAFT. The solubility in mixed solvents is predicted satisfactorily with SciPharma. NRTL-SAC tends to overestimate the solubility in aqueous solutions of alcohols or shows invariable solubility with composition in other cases.

Emergence of Chinese drug discovery research: impact of hit and lead identification.

PubMed

Zhou, Caihong; Zhou, Yan; Wang, Jia; Zhu, Yue; Deng, Jiejie; Wang, Ming-Wei

2015-03-01

The identification of hits and the generation of viable leads is an early and yet crucial step in drug discovery. In the West, the main players of drug discovery are pharmaceutical and biotechnology companies, while in China, academic institutions remain central in the field of drug discovery. There has been a tremendous amount of investment from the public as well as private sectors to support infrastructure buildup and expertise consolidation relative to drug discovery and development in the past two decades. A large-scale compound library has been established in China, and a series of high-impact discoveries of lead compounds have been made by integrating information obtained from different technology-based strategies. Natural products are a major source in China's drug discovery efforts. Knowledge has been enhanced via disruptive breakthroughs such as the discovery of Boc5 as a nonpeptidic agonist of glucagon-like peptide 1 receptor (GLP-1R), one of the class B G protein-coupled receptors (GPCRs). Most of the original hit identification and lead generation were carried out by academic institutions, including universities and specialized research institutes. The Chinese pharmaceutical industry is gradually transforming itself from manufacturing low-end generics and active pharmaceutical ingredients to inventing new drugs. © 2014 Society for Laboratory Automation and Screening.

A derivatization-enhanced detection strategy in mass spectrometry: analysis of 4-hydroxybenzoates and their metabolites after keratinocytes are exposed to UV radiation

PubMed Central

Lee, Yi-Hsuan; Lin, Ying-Chi; Feng, Chia-Hsien; Tseng, Wei-Lung; Lu, Chi-Yu

2017-01-01

4-Hydroxybenzoate is a phenolic derivative of alkyl benzoates and is a widely used preservative in cosmetic and pharmaceutical products. The presence of 4-hydroxybenzoates in the human body may result from the use of pharmaceutical and personal care products. These compounds are also known to exhibit estrogenic and genotoxic activities. The potential adverse effects of these compounds include endocrine disruption, oxidative and DNA damage, contact dermatitis, and allergic reactions. This study used two mass spectrometry methods that are applicable when using a derivatization-enhanced detection strategy (DEDS) to screen 4-hydroxybenzoates and their metabolites. Chemical derivatization was used to enhance the detection of these compounds. To evaluate the metabolic process triggered by UV radiation, human keratinocyte HaCaT cells treated with these 4-hydroxybenzoates were further exposed to UVA, UVB and UVC radiation. Metabolites transformed by human keratinocytes in the chemical derivatization procedure were identified by a nano ultra-performance liquid chromatographic system (nanoUPLC) coupled with LTQ Orbitrap. The experiments confirmed the feasibility of this method for identifying 4-hydroxybenzoate metabolites and for high-throughput screening of 4-hydroxybenzoate in commercial products (50 samples) by the DEDS. PMID:28057923

Limited Influence of Excipients in Extemporaneous Compounded Suspensions

PubMed Central

Dijkers, Eli; Nanhekhan, Valerie; Thorissen, Astrid; Marro, Diego; Uriel, Marta

2017-01-01

Objective: The objective of this study was to identify whether compounding oral suspensions with SyrSpend SF based on tablets or capsules is a suitable alternative for using raw pharmaceutical materials. Methods: Suspensions based on 5 different tablets and capsules were studied in SyrSpend SF. The summary of product characteristics of these different tablets and capsules were obtained from the manufacturer. Our hypothesis was that, if the maximum beyond-use date of the study was reached, the excipient did not seem to have an influence on the stability of the active pharmaceutical ingredient (API) within the studied time frame. Results: All excipients used in flecainide acetate, labetalol HCl, and tiagabine HCl tablets as well as in celecoxib and oseltamivir capsules did not seem to influence the beyond-use date of the overall suspension based on SyrSpend SF. Conclusion: Although using raw materials as API sources is preferred, oral suspensions with SyrSpend SF prepared from crushed tablets or opened capsules could be a possible alternative. Based on this study, a wide range of different excipients does not seem to impact the beyond-use date of different APIs compounded in SyrSpend SF. PMID:29276267

Limited Influence of Excipients in Extemporaneous Compounded Suspensions.

PubMed

Dijkers, Eli; Nanhekhan, Valerie; Thorissen, Astrid; Marro, Diego; Uriel, Marta

2017-06-01

Objective: The objective of this study was to identify whether compounding oral suspensions with SyrSpend SF based on tablets or capsules is a suitable alternative for using raw pharmaceutical materials. Methods: Suspensions based on 5 different tablets and capsules were studied in SyrSpend SF. The summary of product characteristics of these different tablets and capsules were obtained from the manufacturer. Our hypothesis was that, if the maximum beyond-use date of the study was reached, the excipient did not seem to have an influence on the stability of the active pharmaceutical ingredient (API) within the studied time frame. Results: All excipients used in flecainide acetate, labetalol HCl, and tiagabine HCl tablets as well as in celecoxib and oseltamivir capsules did not seem to influence the beyond-use date of the overall suspension based on SyrSpend SF. Conclusion: Although using raw materials as API sources is preferred, oral suspensions with SyrSpend SF prepared from crushed tablets or opened capsules could be a possible alternative. Based on this study, a wide range of different excipients does not seem to impact the beyond-use date of different APIs compounded in SyrSpend SF.

Sorption, photodegradation, and chemical transformation of naproxen and ibuprofen in soils and water.

PubMed

Vulava, Vijay M; Cory, Wendy C; Murphey, Virginia L; Ulmer, Candice Z

2016-09-15

Pharmaceutically active compounds (PhACs) are released into the environment where they undergo soil sorption, photodegradation, and chemical transformation into structurally similar compounds. Here we report on studies of naproxen (NAP) and ibuprofen (IBP), two widely-used nonsteroidal anti-inflammatory drugs (NSAIDS), in soils and water. Organic matter (OM) was observed to play an important role in each of these processes. Sorption was observed to be stronger and nonlinear in higher OM soils while weaker but still significant in lower OM, higher clay soils; the amphiphilic nature of these two PhACs combined with the complex charged and nonpolar surfaces available in the soil was observed to control the sorption behavior. Simulated solar photodegradation rates of NAP and IBP in water were observed to change in the presence of humic acid or fulvic acid. Structural analogs of each compound were observed as the result of chemical transformation in both photoexposed aqueous solutions and non-photoexposed soil. Two of these transformation products were detected as both soil and photo transformation products for both PhACs. OM was observed to influence the chemical transformation of both pharmaceuticals. Copyright © 2016 Elsevier B.V. All rights reserved.

An uncertainty and sensitivity analysis applied to the prioritisation of pharmaceuticals as surface water contaminants from wastewater treatment plant direct emissions.

PubMed

Morais, Sérgio Alberto; Delerue-Matos, Cristina; Gabarrell, Xavier

2014-08-15

In this study, the concentration probability distributions of 82 pharmaceutical compounds detected in the effluents of 179 European wastewater treatment plants were computed and inserted into a multimedia fate model. The comparative ecotoxicological impact of the direct emission of these compounds from wastewater treatment plants on freshwater ecosystems, based on a potentially affected fraction (PAF) of species approach, was assessed to rank compounds based on priority. As many pharmaceuticals are acids or bases, the multimedia fate model accounts for regressions to estimate pH-dependent fate parameters. An uncertainty analysis was performed by means of Monte Carlo analysis, which included the uncertainty of fate and ecotoxicity model input variables, as well as the spatial variability of landscape characteristics on the European continental scale. Several pharmaceutical compounds were identified as being of greatest concern, including 7 analgesics/anti-inflammatories, 3 β-blockers, 3 psychiatric drugs, and 1 each of 6 other therapeutic classes. The fate and impact modelling relied extensively on estimated data, given that most of these compounds have little or no experimental fate or ecotoxicity data available, as well as a limited reported occurrence in effluents. The contribution of estimated model input variables to the variance of freshwater ecotoxicity impact, as well as the lack of experimental abiotic degradation data for most compounds, helped in establishing priorities for further testing. Generally, the effluent concentration and the ecotoxicity effect factor were the model input variables with the most significant effect on the uncertainty of output results. Copyright © 2014. Published by Elsevier B.V.

The Occurrence of Veterinary Pharmaceuticals in the Environment: A Review

PubMed Central

Kaczala, Fabio; Blum, Shlomo E.

2016-01-01

It is well known that there is a widespread use of veterinary pharmaceuticals and consequent release into different ecosystems such as freshwater bodies and groundwater systems. Furthermore, the use of organic fertilizers produced from animal waste manure has been also responsible for the occurrence of veterinary pharmaceuticals in agricultural soils. This article is a review of different studies focused on the detection and quantification of such compounds in environmental compartments using different analytical techniques. Furthermore, this paper reports the main challenges regarding veterinary pharmaceuticals in terms of analytical methods, detection/quantification of parent compounds and metabolites, and risks/toxicity to human health and aquatic ecosystems. Based on the existing literature, it is clear that only limited data is available regarding veterinary compounds and there are still considerable gaps to be bridged in order to remediate existing problems and prevent future ones. In terms of analytical methods, there are still considerable challenges to overcome considering the large number of existing compounds and respective metabolites. A number of studies highlight the lack of attention given to the detection and quantification of transformation products and metabolites. Furthermore more attention needs to be given in relation to the toxic effects and potential risks that veterinary compounds pose to environmental and human health. To conclude, the more research investigations focused on these subjects take place in the near future, more rapidly we will get a better understanding about the behavior of these compounds and the real risks they pose to aquatic and terrestrial environments and how to properly tackle them. PMID:28579931

[Written pharmaceutical advertising--still unreliable?].

PubMed

Gladsø, Kristin Haugen; Garberg, Hedda Rosland; Spigset, Olav; Slørdal, Lars

2014-09-02

Marketing by the pharmaceutical industry affects doctors' prescribing habits. All pharmaceutical advertising received by nine doctors in two GP offices over a period of three months was collected. The advertising material was sorted by compound. For each compound, the advert with the highest number of references was selected. The cited references were obtained, and the claims in the adverts were assessed in terms of their consistency with the source data based on the provisions in the Norwegian regulations on pharmaceuticals. The references were also assessed with regard to the incidence of conflicts of interest among authors. The doctors received a total of 270 shipments of advertising for 46 different compounds. Altogether 95% of the 173 references cited in the 46 selected adverts could be obtained. The adverts contained a total of 156 claims. Of these, 56% were assessed as correct when compared to the source data and as having clinical relevance. Altogether 75% of the journal articles reported relevant conflicts of interest for the authors. About half the claims in the adverts were found to be correct and clinically relevant. These results concur with those from a methodologically identical study based on advertising material collected in 2004. The cited literature was of varying quality and often funded by the pharmaceutical companies. The findings indicate that the target group should be sceptical of this type of marketing.

Hypopigmenting Effects of Brown Algae-Derived Phytochemicals: A Review on Molecular Mechanisms

PubMed Central

Azam, Mohammed Shariful; Choi, Jinkyung; Lee, Min-Sup; Kim, Hyeung-Rak

2017-01-01

There is a rapid increase in the demand for natural hypopigmenting agents from marine sources for cosmeceutical and pharmaceutical applications. Currently, marine macroalgae are considered as a safe and effective source of diverse bioactive compounds. Many research groups are exploring marine macroalgae to discover and characterize novel compounds for cosmeceutical, nutraceutical, and pharmaceutical applications. Many types of bioactive secondary metabolites from marine algae, including phlorotannins, sulfated polysaccharides, carotenoids, and meroterpenoids, have already been documented for their potential applications in the pharmaceutical industry. Among these metabolites, phlorotannins from brown algae have been widely screened for their pharmaceutical and hypopigmenting effects. Unfortunately, the majority of these articles did not have detailed investigations on molecular targets, which is critical to fulfilling the criteria for their cosmeceutical and pharmaceutical use. Very recently, a few meroterpenoids have been discovered from Sargassum sp., with the examination of their anti-melanogenic properties and mechanisms. Despite the scarcity of in vivo and clinical investigations of molecular mechanistic events of marine algae-derived hypopigmenting agents, identifying the therapeutic targets and their validation in humans has been a major challenge for future studies. In this review, we focused on available data representing molecular mechanisms underlying hypopigmenting properties of potential marine brown alga-derived compounds. PMID:28946635

Isoflavones from green vegetable soya beans and their antimicrobial and antioxidant activities.

PubMed

Wang, Taoyun; Liu, Yanli; Li, Xiaoran; Xu, Qiongming; Feng, Yulin; Yang, Shilin

2018-03-01

Green vegetable soya beans, known as Maodou in China, are supplied as vegetable-type fruits of the soybean plant. Previous study indicated that green vegetable soya beans exhibited antioxidative and anti-inflammatory activities. However, the material basis and pharmacological activities of green soybean plant were not unravelled clearly. In this study, we investigated the chemical ingredients and their pharmacological activities. Investigation of the chemical ingredients indicated that two new isoflavones, 2'-hydroxyerythrin A (1), and daidzein-7-O-β-d-{6″-[(E)-but-2-enoyl]}glycoside (2), together with seven known ones - 7,4'-dihydroxy-6-methoxyisoflavone (3), daidzein (4), daidzin (5), genistein (6), formononetin (7), ononin (8), and isoerythrinin A (9) - were obtained. The structures of compounds 1-9 were elucidated on the basis of spectroscopic and chemical analysis. We evaluated the antimicrobial efficacies and free-radical scavenging potential of the isolated compounds (1-9). Compounds 1 and 9 exhibited the most pronounced efficacy against the tested bacterial strains with IC 50 values ranging from 10.6 to 22.6 μg mL -1 . The isolated compounds showed moderate radical scavenging properties with compound 6 being the most active, followed by compounds 3, 1 and 4. This study indicated that the isoflavones from soya beans could be considered as potential antioxidants or antimicrobials in the food, cosmetics and pharmaceutical industries. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The Daniel K. Inouye College of Pharmacy Scripts: Poha Berry (Physalis peruviana) with Potential Anti-inflammatory and Cancer Prevention Activities.

PubMed

Chang, Leng Chee; Sang-Ngern, Mayuramas; Pezzuto, John M; Ma, Carolyn

2016-11-01

The Daniel K. Inouye College of Pharmacy, during a historic event in Spring 2016, graduated the first two students in the Pacific region to earn a PhD in pharmaceutical sciences at the University of Hawai'i at Hilo. The college offers PhD programs in these five disciplines: Cancer Biology, Medicinal Chemistry, Pharmaceutics, Pharmacognosy, and Pharmacology. One of the Pharmacognosy dissertations focused on plant-derived natural products with potential anti-inflammatory and cancer chemopreventive activities. Physalis peruviana (Pp) L. originated in tropical South America. It has become naturalized and is found readily on the Island of Hawai'i. The edible fruits are commonly known as cape gooseberry or poha in Hawai'i. In part of our study, three new withanolides, physaperuvin G ( 1 ), physaperuvins I-J ( 2 - 3 ), along with four known withanolides, namely, 4β-hydroxywithanolide E ( 4 ), withaperuvin C ( 5 ), and physalactone ( 6 ), coagulin ( 7 ) were isolated from the aerial parts of P. peruviana . In addition, two known compounds, phyperunolide F ( 8 ), and withanolide S ( 9 ), were isolated and identified from the poha berry fruits. The structures and absolute stereochemistry of new compounds from poha were elucidated by several spectroscopy methods: Nuclear Magnetic Resonance (NMR) spectroscopy, X-ray diffraction, and mass spectrometry analyses. All isolated poha compounds (aerial parts and fruits) were evaluated for their anti-inflammatory activity with lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells, and tumor necrosis factor alpha (TNF-α)-activated nuclear factor-kappa B (NF-κB) with transfected human embryonic kidney cells 293. Most of the isolated natural compounds showed activity with these assays. Additional studies were performed with models of colon cancer. Specifically, 4β-hydroxywithanolide E (4HWE) inhibited the growth of colon cancer monolayer and spheroid cultures. The compound induced cell cycle arrest at low concentrations and apoptosis at higher concentrations. These data suggest the ingestion of poha berries may have some effect on the prevalence of colon cancer. Additionally, poha isolates compounds were evaluated for their growth inhibitory effects with U251MG glioblastoma and MDA-MB-231 breast cancer cells that harbor aberrantly-active signal transducer and activation of transcription 3 (STAT3), compared to normal NIH-3T3 mouse fibroblasts. This work has led to the filing of three provisional patents with the University of Hawai'i Office of Technology Transfer and Economic Development.

Direct analysis in real time--high resolution mass spectrometry as a valuable tool for the pharmaceutical drug development.

PubMed

Srbek, Jan; Klejdus, Bořivoj; Douša, Michal; Břicháč, Jiří; Stasiak, Pawel; Reitmajer, Josef; Nováková, Lucie

2014-12-01

In this study, direct analysis in real time-mass spectrometry (DART-MS) was assessed for the analysis of various pharmaceutical formulations with intention to summarize possible applications for the routine pharmaceutical development. As DART is an ambient ionization technique, it allows direct analysis of pharmaceutical samples in solid or liquid form without complex sample preparation, which is often the most time-consuming part of the analytical method. This makes the technique suitable for many application fields, including pharmaceutical drug development. DART mass spectra of more than twenty selected tablets and other common pharmaceutical formulations, i.e. injection solutions, ointments and suppositories developed in the pharmaceutical industry during several recent years are presented. Moreover, as thin-layer chromatography (TLC) is still very popular for the monitoring of the reactions in the synthetic chemistry, several substances were analyzed directly from the TLC plates to demonstrate the simplicity of the technique. Pure substance solutions were spotted onto a TLC plate and then analyzed with DART without separation. This was the first DART-MS study of pharmaceutical dosage forms using DART-Orbitrap combination. The duration of sample analysis by the DART-MS technique lasted several seconds, allowing enough time to collect sufficient number of data points for compound identification. The experimental setup provided excellent mass accuracy and high resolution of the mass spectra which allowed unambiguous identification of the compounds of interest. Finally, DART mass spectrometry was also used for the monitoring of the selected impurity distribution in the atorvastatin tablets. These measurements demonstrated DART to be robust ionization technique, which provided easy-to-interpret mass spectra for the broad range of compounds. DART has high-throughput potential for various types of pharmaceutical analyses and therefore eliminates the time for sample cleanup and chromatographic separation. Copyright © 2014 Elsevier B.V. All rights reserved.

BIOTECHNOLOGY, NANOTECHNOLOGY, AND PHARMACOGENOMICS AND PHARMACEUTICAL COMPOUNDING, PART 2.

PubMed

Allen, Loyd V

2015-01-01

This article, which represents part 2 of a two part article, completes the discussion on the rapidly changing world of pharmaceuticals as biotechnology continues to grow and nanotechnology appears on the horizon.

Adsorption of selected endocrine disrupting compounds and pharmaceuticals on activated biochars.

PubMed

Jung, Chanil; Park, Junyeong; Lim, Kwang Hun; Park, Sunkyu; Heo, Jiyong; Her, Namguk; Oh, Jeill; Yun, Soyoung; Yoon, Yeomin

2013-12-15

Chemically activated biochar produced under oxygenated (O-biochar) and oxygen-free (N-biochar) conditions were characterized and the adsorption of endocrine disrupting compounds (EDCs): bisphenol A (BPA), atrazine (ATR), 17 α-ethinylestradiol (EE2), and pharmaceutical active compounds (PhACs); sulfamethoxazole (SMX), carbamazepine (CBM), diclofenac (DCF), ibuprofen (IBP) on both biochars and commercialized powdered activated carbon (PAC) were investigated. Characteristic analysis of adsorbents by solid-state nuclear magnetic resonance (NMR) was conducted to determine better understanding about the EDCs/PhACs adsorption. N-biochar consisted of higher polarity moieties with more alkyl (0-45 ppm), methoxyl (45-63 ppm), O-alkyl (63-108 ppm), and carboxyl carbon (165-187 ppm) content than other adsorbents, while aromaticity of O-biochar was higher than that of N-biochar. O-biochar was composed mostly of aromatic moieties, with low H/C and O/C ratios compared to the highly polarized N-biochar that contained diverse polar functional groups. The higher surface area and pore volume of N-biochar resulted in higher adsorption capacity toward EDCs/PhACs along with atomic-level molecular structural property than O-biochar and PAC. N-biochar had a highest adsorption capacity of all chemicals, suggesting that N-biochar derived from loblolly pine chip is a promising sorbent for agricultural and environmental applications. The adsorption of pH-sensitive dissociable SMX, DCF, IBP, and BPA varied and the order of adsorption capacity was correlated with the hydrophobicity (Kow) of adsorbates throughout the all adsorbents, whereas adsorption of non-ionizable CBM, ATR, and EE2 in varied pH allowed adsorbents to interact with hydrophobic property of adsorbates steadily throughout the study. Copyright © 2013 Elsevier B.V. All rights reserved.

Gamma sterilization of pharmaceuticals--a review of the irradiation of excipients, active pharmaceutical ingredients, and final drug product formulations.

PubMed

Hasanain, Fatima; Guenther, Katharina; Mullett, Wayne M; Craven, Emily

2014-01-01

Sterilization by gamma irradiation has shown a strong applicability for a wide range of pharmaceutical products. Due to the requirement for terminal sterilization where possible in the pharmaceutical industry, gamma sterilization has proven itself to be an effective method as indicated by its acceptance in the European Pharmacopeia and the United States Pharmacopeia ( ). Some of the advantages of gamma over competitive procedures include high penetration power, isothermal character (small temperature rise), and no residues. It also provides a better assurance of product sterility than aseptic processing, as well as lower validation demands. Gamma irradiation is capable of killing microorganisms by breaking their chemical bonds, producing free radicals that attack the nucleic acid of the microorganism. Sterility by gamma irradiation is achieved mainly by the alteration of nucleic acid and preventing the cellular division. This review focuses on the extensive application of gamma sterilization to a wide range of pharmaceutical components including active pharmaceutical ingredients, excipients, final drug products, and combination drug-medical devices. A summary of the published literature for each class of pharmaceutical compound or product is presented. The irradiation conditions and various quality control characterization methodologies that were used to determine final product quality are included, in addition to a summary of the investigational outcomes. Based on this extensive literature review and in combination with regulatory guidelines and other published best practices, a decision tree for implementation of gamma irradiation for pharmaceutical products is established. This flow chart further facilitates the implementation of gamma irradiation in the pharmaceutical development process. The summary therefore provides a useful reference to the application and versatility of gamma irradiation for pharmaceutical sterilization. Many pharmaceutical products require sterilization to ensure their safe and effective use. Sterility is therefore a critical quality attribute and is essential for direct injection products. Due to the requirement for terminal sterilization, where possible in the pharmaceutical industry sterilization by gamma irradiation has been commonly used as an effective method to sterilize pharmaceutical products as indicated by its acceptance in the European Pharmacopeia. Gamma sterilization is a very attractive terminal sterilization method in view of its ability to attain 10(-6) probability of microbial survival without excessive heating of the product or exposure to toxic chemicals. However, radiation compatibility of a product is one of the first aspects to evaluate when considering gamma sterilization. Gamma radiation consists of high-energy photons that result in the generation of free radicals and the subsequent ionization of chemical bonds, leading to cleavage of DNA in microorganisms and their subsequent inactivation. This can result in a loss of active pharmaceutical ingredient potency, the creation of radiolysis by-products, a reduction of the molecular weight of polymer excipients, and influence drug release from the final product. There are several strategies for mitigating degradation effects, including optimization of the irradiation dose and conditions. This review will serve to highlight the extensive application of gamma sterilization to a broad spectrum of pharmaceutical components including active pharmaceutical ingredients, excipients, final drug products, and combination drug-medical devices.

Water-quality assessment of the largely urban blue river basin, Metropolitan Kansas City, USA, 1998 to 2007

USGS Publications Warehouse

Wilkison, D.H.; Armstrong, D.J.; Hampton, S.A.

2009-01-01

From 1998 through 2007, over 750 surface-water or bed-sediment samples in the Blue River Basin - a largely urban basin in metropolitan Kansas City - were analyzed for more than 100 anthropogenic compounds. Compounds analyzed included nutrients, fecal-indicator bacteria, suspended sediment, pharmaceuticals and personal care products. Non-point source runoff, hydrologic alterations, and numerous waste-water discharge points resulted in the routine detection of complex mixtures of anthropogenic compounds in samples from basin stream sites. Temporal and spatial variations in concentrations and loads of nutrients, pharmaceuticals, and organic wastewater compounds were observed, primarily related to a site's proximity to point-source discharges and stream-flow dynamics. ?? 2009 ASCE.

Seasonal variation of endocrine disrupting compounds, pharmaceuticals and personal care products in wastewater treatment plants.

PubMed

Yu, Yong; Wu, Laosheng; Chang, Andrew C

2013-01-01

The occurrence of 14 endocrine disrupting compounds (EDCs), pharmaceuticals and personal care products (PPCPs) in influents, effluents and sludge from five wastewater treatment plants (WWTPs) in southern California was studied in winter and summer. All 14 compounds were detected in influent samples from the five WWTPs except for estrone. Paracetamol, naproxen and ibuprofen were the dominant compounds, with mean concentrations of 41.7, 35.7 and 22.3 μg/L, respectively. The treatment removal efficiency for most compounds was more than 90% and concentrations in the effluents were relatively low. Seasonal variation of the compounds' concentration in the wastewater was significant: the total concentration of each compound in the wastewater was higher in winter than in summer, which is attributed to more human consumption of pharmaceuticals during winter and faster degradation of the compounds in summer. The highest concentrations of triclosan and octylphenol were detected in sewage sludge, with mean concentrations of 1505 and 1179 ng/g, respectively. Risk quotients (RQs), expressed as the ratios of environmental concentrations and the predicted no-effect concentrations (PNEC), were less than unity for all the compounds except for estrone in the effluents, indicating no immediate ecological risk is expected. However, RQs were higher than unity for 2 EDCs (estrone and octylphenol) and carbamazepine in sludge samples, indicating a significant ecotoxicological risk to human health. Therefore, appropriate treatment of sewage sludge is required before its application. Copyright © 2012 Elsevier B.V. All rights reserved.

Fate of pharmaceuticals in full-scale source separated sanitation system.

PubMed

Butkovskyi, A; Hernandez Leal, L; Rijnaarts, H H M; Zeeman, G

2015-11-15

Removal of 14 pharmaceuticals and 3 of their transformation products was studied in a full-scale source separated sanitation system with separate collection and treatment of black water and grey water. Black water is treated in an up-flow anaerobic sludge blanket (UASB) reactor followed by oxygen-limited autotrophic nitrification-denitrification in a rotating biological contactor and struvite precipitation. Grey water is treated in an aerobic activated sludge process. Concentration of 10 pharmaceuticals and 2 transformation products in black water ranged between low μg/l to low mg/l. Additionally, 5 pharmaceuticals were also present in grey water in low μg/l range. Pharmaceutical influent loads were distributed over two streams, i.e. diclofenac was present for 70% in grey water, while the other compounds were predominantly associated to black water. Removal in the UASB reactor fed with black water exceeded 70% for 9 pharmaceuticals out of the 12 detected, with only two pharmaceuticals removed by sorption to sludge. Ibuprofen and the transformation product of naproxen, desmethylnaproxen, were removed in the rotating biological contactor. In contrast, only paracetamol removal exceeded 90% in the grey water treatment system while removal of other 7 pharmaceuticals was below 40% or even negative. The efficiency of pharmaceutical removal in the source separated sanitation system was compared with removal in the conventional sewage treatment plants. Furthermore, effluent concentrations of black water and grey water treatment systems were compared with predicted no-effect concentrations to assess toxicity of the effluent. Concentrations of diclofenac, ibuprofen and oxazepam in both effluents were higher than predicted no-effect concentrations, indicating the necessity of post-treatment. Ciprofloxacin, metoprolol and propranolol were found in UASB sludge in μg/g range, while pharmaceutical concentrations in struvite did not exceed the detection limits. Copyright © 2015 Elsevier Ltd. All rights reserved.

In silico prediction of pharmaceutical degradation pathways: a benchmarking study.

PubMed

Kleinman, Mark H; Baertschi, Steven W; Alsante, Karen M; Reid, Darren L; Mowery, Mark D; Shimanovich, Roman; Foti, Chris; Smith, William K; Reynolds, Dan W; Nefliu, Marcela; Ott, Martin A

2014-11-03

Zeneth is a new software application capable of predicting degradation products derived from small molecule active pharmaceutical ingredients. This study was aimed at understanding the current status of Zeneth's predictive capabilities and assessing gaps in predictivity. Using data from 27 small molecule drug substances from five pharmaceutical companies, the evolution of Zeneth predictions through knowledge base development since 2009 was evaluated. The experimentally observed degradation products from forced degradation, accelerated, and long-term stability studies were compared to Zeneth predictions. Steady progress in predictive performance was observed as the knowledge bases grew and were refined. Over the course of the development covered within this evaluation, the ability of Zeneth to predict experimentally observed degradants increased from 31% to 54%. In particular, gaps in predictivity were noted in the areas of epimerizations, N-dealkylation of N-alkylheteroaromatic compounds, photochemical decarboxylations, and electrocyclic reactions. The results of this study show that knowledge base development efforts have increased the ability of Zeneth to predict relevant degradation products and aid pharmaceutical research. This study has also provided valuable information to help guide further improvements to Zeneth and its knowledge base.

NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database

PubMed Central

Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P. S.; Agarwal, Subhash M.

2013-01-01

Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC50/ED50/EC50/GI50), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients’ Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI50 data. PMID:23203877

An automated synthesis-purification-sample-management platform for the accelerated generation of pharmaceutical candidates.

PubMed

Sutherland, J David; Tu, Noah P; Nemcek, Thomas A; Searle, Philip A; Hochlowski, Jill E; Djuric, Stevan W; Pan, Jeffrey Y

2014-04-01

A flexible and integrated flow-chemistry-synthesis-purification compound-generation and sample-management platform has been developed to accelerate the production of small-molecule organic-compound drug candidates in pharmaceutical research. Central to the integrated system is a Mitsubishi robot, which hands off samples throughout the process to the next station, including synthesis and purification, sample dispensing for purity and quantification analysis, dry-down, and aliquot generation.

Biogenic platinum and palladium nanoparticles as new catalysts for the removal of pharmaceutical compounds.

PubMed

Martins, Mónica; Mourato, Cláudia; Sanches, Sandra; Noronha, João Paulo; Crespo, M T Barreto; Pereira, Inês A C

2017-01-01

Pharmaceutical products (PhP) are one of the most alarming emergent pollutants in the environment. Therefore, it is of extreme importance to investigate efficient PhP removal processes. Biologic synthesis of platinum nanoparticles (Bio-Pt) has been reported, but their catalytic activity was never investigated. In this work, we explored the potential of cell-supported platinum (Bio-Pt) and palladium (Bio-Pd) nanoparticles synthesized with Desulfovibrio vulgaris as biocatalysts for removal of four PhP: ciprofloxacin, sulfamethoxazole, ibuprofen and 17β-estradiol. The catalytic activity of the biological nanoparticles was compared with the PhP removal efficiency of D. vulgaris whole-cells. In contrast with Bio-Pd, Bio-Pt has a high catalytic activity in PhP removal, with 94, 85 and 70% removal of 17β-estradiol, sulfamethoxazole and ciprofloxacin, respectively. In addition, the estrogenic activity of 17β-estradiol was strongly reduced after the reaction with Bio-Pt, showing that this biocatalyst produces less toxic effluents. Bio-Pt or Bio-Pd did not act on ibuprofen, but this could be completely removed by D. vulgaris whole-cells, demonstrating that sulfate-reducing bacteria are among the microorganisms capable of biotransformation of ibuprofen in anaerobic environments. This study demonstrates for the first time that Bio-Pt has a high catalytic activity, and is a promising catalyst to be used in water treatment processes for the removal of antibiotics and endocrine disrupting compounds, the most problematic PhP. Copyright © 2016 Elsevier Ltd. All rights reserved.

New antibiotic agents in the pipeline and how they can help overcome microbial resistance

PubMed Central

Gould, Ian M.; Bal, Abhijit M.

2013-01-01

Bacterial resistance is a growing threat and yet few new antibiotics active against multi-resistant bacteria are being explored. A combination of falling profits, regulatory mechanisms and irrational and injudicious use of antibiotics has led to an alarming situation where some infections have no cure. In this article, we summarize the new developments that have been suggested to incentivize the pharmaceutical industries toward the field of infections. We also briefly mention the new compounds on the horizon and some newly approved compounds that might help us tide over this crisis. PMID:23302792

New antibiotic agents in the pipeline and how they can help overcome microbial resistance.

PubMed

Gould, Ian M; Bal, Abhijit M

2013-02-15

Bacterial resistance is a growing threat and yet few new antibiotics active against multi-resistant bacteria are being explored. A combination of falling profits, regulatory mechanisms and irrational and injudicious use of antibiotics has led to an alarming situation where some infections have no cure. In this article, we summarize the new developments that have been suggested to incentivize the pharmaceutical industries toward the field of infections. We also briefly mention the new compounds on the horizon and some newly approved compounds that might help us tide over this crisis.

The Evaluation and Utilization of Marine-derived Bioactive Compounds with Anti-obesity Effect.

PubMed

Jin, Qiu; Yu, Huahua; Li, Pengcheng

2018-01-01

Obesity is a global epidemic throughout the world. There is thus increasing interest in searching for natural bioactive compounds with anti-obesity effect. A number of marine compounds have been regarded as potential sources of bioactive compounds and are associated with an anti-obesity effect. Marine-derived compounds with anti-obesity effect and their current applications, methods and indicators for the evaluation of anti-obesity activity are summarized in this review. in order to make contributions to the development of marine-derived functional food against obesity. In this review, an overview of marine-derived compounds with anti-obesity effect, including marine polysaccharides, marine lipid, marine peptides, marine carotenoids is intensively made with an emphasis on their efficacy and mechanism of action. Meanwhile, methods and indicators for the evaluation of anti-obesity activity are discussed. We summarize these methods into three categories: in vitro assay (including adsorption experiments and enzyme inhibitory assay), cell line study, animal experiments and clinical experiments. In addition, a brief introduction of the current applications of marine bioactive compounds with anti-obesity activity is discussed. Marine environment is a rich source of both biological and chemical diversity. In the past decades, numerous novel compounds with anti-obesity activity have been obtained from marine organisms, and many of them have been applied to industrial production such as functional foods and pharmaceuticals. Further studies are needed to explore the above-mentioned facts. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Application of the threshold of toxicological concern concept to pharmaceutical manufacturing operations.

PubMed

Dolan, David G; Naumann, Bruce D; Sargent, Edward V; Maier, Andrew; Dourson, Michael

2005-10-01

A scientific rationale is provided for estimating acceptable daily intake values (ADIs) for compounds with limited or no toxicity information to support pharmaceutical manufacturing operations. These ADIs are based on application of the "thresholds of toxicological concern" (TTC) principle, in which levels of human exposure are estimated that pose no appreciable risk to human health. The same concept has been used by the US Food and Drug Administration (FDA) to establish "thresholds of regulation" for indirect food additives and adopted by the Joint FAO/WHO Expert Committee on Food Additives for flavoring substances. In practice, these values are used as a statement of safety and indicate when no actions need to be taken in a given exposure situation. Pharmaceutical manufacturing relies on ADIs for cleaning validation of process equipment and atypical extraneous matter investigations. To provide practical guidance for handling situations where relatively unstudied compounds with limited or no toxicity data are encountered, recommendations are provided on ADI values that correspond to three categories of compounds: (1) compounds that are likely to be carcinogenic, (2) compounds that are likely to be potent or highly toxic, and (3) compounds that are not likely to be potent, highly toxic or carcinogenic. Corresponding ADIs for these categories of materials are 1, 10, and 100 microg/day, respectively.

Time-course measurements of drug concentrations in hair and toenails after single administrations of pharmaceutical products.

PubMed

Kuwayama, Kenji; Miyaguchi, Hajime; Iwata, Yuko T; Kanamori, Tatsuyuki; Tsujikawa, Kenji; Yamamuro, Tadashi; Segawa, Hiroki; Inoue, Hiroyuki

2017-04-01

Hair and nails are often used to prove long-term intake of drugs in forensic drug testing. The aim of this study was to evaluate the effectiveness of drug testing using hair and nails and the feasibility of determining when drugs were ingested by measuring the time-courses of drug concentrations in hair and toenails after single administrations of various drugs. Healthy subjects ingested four pharmaceutical products containing eight active ingredients in single doses. Hair and toenails were collected at predetermined intervals, and drug concentrations in hair and nails were measured for 12 months. The administered drugs and their main metabolites were extracted using micropulverized extraction with a stainless steel bullet and were analyzed using liquid chromatography/tandem mass spectrometry. Acidic compounds such as ibuprofen and its metabolites were not detected in both specimens. Acetaminophen, a weakly acidic compound, was detected in nails more frequently than in hair. The maximum concentration of allyl isopropyl acetylurea, a neutral compound, in nails was significantly higher than in hair. Nails are an effective specimen to detect neutral and weakly acidic compounds. For fexofenadine, a zwitterionic compound, and for most basic compounds, the maximum concentrations in hair segments tended to be higher than those in nails. The hair segments showing the maximum concentrations varied between drugs, samples, and subjects. Drug concentrations in hair segments greatly depended on the selection of the hair. Careful interpretation of analytical results is required to predict the time of drug intake. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Application of Polar Organic Chemical Integrative Sampler (POCIS) to monitor emerging contaminants in tropical waters.

PubMed

Bayen, Stéphane; Segovia, Elvagris; Loh, Lay Leng; Burger, David F; Eikaas, Hans S; Kelly, Barry C

2014-06-01

Tools specifically validated for tropical environments are needed to accurately describe the behavior of chemical contaminants in tropical ecosystems. In the present study, sampling rates (Rs) were determined for the commercial pharmaceutical-type Polar Organic Chemical Integrative Sampler (POCIS) with a 45.8cm(2) exposure surface for 35 Pharmaceutically Active Compounds (PhACs) and Endocrine Disrupting Compounds (EDCs), of which eight compounds (albuterol, atorvastatin, diltiazem, dilantin, enalapril, norfluoxetine, risperidone and warfarin) were reported for the first time. These sampling rates were measured in an outdoor laboratory calibration setup to best capture diurnal tropical temperature variations (29±3°C). The effect of stirring and salinity was investigated. For all compounds, the sampling rates were higher under stirred conditions as compared to quiescent conditions. Calibration results in the presence of 30g sodium chloride support that the effects of salinity on POCIS sampling rates are compound-specific. Comparisons between Time-Weight Average (TWA) water concentrations using POCIS and spot sample levels in the field (2 lake and 1 mangrove estuary sites) are presented. Results showed that POCIS TWA concentrations were in agreement with spot sample concentrations for these aquatic systems. Results indicate that POCIS can be used to effectively measure the TWA concentration for a range of PhACs and EDCs in tropical waters. However, based on the results from mass balance and field deployments, POCIS did not appear suitable for compounds with a low mass balance recovery during calibration (e.g. triclosan and linuron in this study). Copyright © 2014 Elsevier B.V. All rights reserved.

Assessment of the Presence of Pharmaceutical Compounds in Seawater Samples from Coastal Area of Gran Canaria Island (Spain)

PubMed Central

Afonso-Olivares, Cristina; Torres-Padrón, Mª Esther; Sosa-Ferrera, Zoraida; Santana-Rodríguez, José Juan

2013-01-01

This study presents the evaluation of seven pharmaceutical compounds belonging to different commonly used therapeutic classes in seawater samples from coastal areas of Gran Canaria Island. The target compounds include atenolol (antihypertensive), acetaminophen (analgesic), norfloxacin and ciprofloxacin (antibiotics), carbamazepine (antiepileptic) and ketoprofen and diclofenac (anti-inflammatory). Solid phase extraction (SPE) was used for the extraction and preconcentration of the samples, and liquid chromatography tandem mass spectrometry (LC-MS/MS) was used for the determination of the compounds. Under optimal conditions, the recoveries obtained were in the range of 78.3% to 98.2%, and the relative standard deviations were less than 11.8%. The detection and quantification limits of the method were in the ranges of 0.1–2.8 and 0.3–9.3 ng·L−1, respectively. The developed method was applied to evaluate the presence of these pharmaceutical compounds in seawater from four outfalls in Gran Canaria Island (Spain) during one year. Ciprofloxacin and norfloxacin were found in a large number of samples in a concentration range of 9.0–3551.7 ng·L−1. Low levels of diclofenac, acetaminophen and ketoprofen were found sporadically. PMID:27029304

Automated Solid Phase Extraction (SPE) LC/NMR Applied to the Structural Analysis of Extractable Compounds from a Pharmaceutical Packaging Material of Construction.

PubMed

Norwood, Daniel L; Mullis, James O; Davis, Mark; Pennino, Scott; Egert, Thomas; Gonnella, Nina C

2013-01-01

The structural analysis (i.e., identification) of organic chemical entities leached into drug product formulations has traditionally been accomplished with techniques involving the combination of chromatography with mass spectrometry. These include gas chromatography/mass spectrometry (GC/MS) for volatile and semi-volatile compounds, and various forms of liquid chromatography/mass spectrometry (LC/MS or HPLC/MS) for semi-volatile and relatively non-volatile compounds. GC/MS and LC/MS techniques are complementary for structural analysis of leachables and potentially leachable organic compounds produced via laboratory extraction of pharmaceutical container closure/delivery system components and corresponding materials of construction. Both hyphenated analytical techniques possess the separating capability, compound specific detection attributes, and sensitivity required to effectively analyze complex mixtures of trace level organic compounds. However, hyphenated techniques based on mass spectrometry are limited by the inability to determine complete bond connectivity, the inability to distinguish between many types of structural isomers, and the inability to unambiguously determine aromatic substitution patterns. Nuclear magnetic resonance spectroscopy (NMR) does not have these limitations; hence it can serve as a complement to mass spectrometry. However, NMR technology is inherently insensitive and its ability to interface with chromatography has been historically challenging. This article describes the application of NMR coupled with liquid chromatography and automated solid phase extraction (SPE-LC/NMR) to the structural analysis of extractable organic compounds from a pharmaceutical packaging material of construction. The SPE-LC/NMR technology combined with micro-cryoprobe technology afforded the sensitivity and sample mass required for full structure elucidation. Optimization of the SPE-LC/NMR analytical method was achieved using a series of model compounds representing the chemical diversity of extractables. This study demonstrates the complementary nature of SPE-LC/NMR with LC/MS for this particular pharmaceutical application. The identification of impurities leached into drugs from the components and materials associated with pharmaceutical containers, packaging components, and materials has historically been done using laboratory techniques based on the combination of chromatography with mass spectrometry. Such analytical techniques are widely recognized as having the selectivity and sensitivity required to separate the complex mixtures of impurities often encountered in such identification studies, including both the identification of leachable impurities as well as potential leachable impurities produced by laboratory extraction of packaging components and materials. However, while mass spectrometry-based analytical techniques have limitations for this application, newer analytical techniques based on the combination of chromatography with nuclear magnetic resonance spectroscopy provide an added dimension of structural definition. This article describes the development, optimization, and application of an analytical technique based on the combination of chromatography and nuclear magnetic resonance spectroscopy to the identification of potential leachable impurities from a pharmaceutical packaging material. The complementary nature of the analytical techniques for this particular pharmaceutical application is demonstrated.

Targeted polypeptide degradation

DOEpatents

Church, George M [Brookline, MA; Janse, Daniel M [Brookline, MA

2008-05-13

This invention pertains to compositions, methods, cells and organisms useful for selectively localizing polypeptides to the proteasome for degradation. Therapeutic methods and pharmaceutical compositions for treating disorders associated with the expression and/or activity of a polypeptide by targeting these polypeptides for degradation, as well as methods for targeting therapeutic polypeptides for degradation and/or activating therapeutic polypeptides by degradation are provided. The invention provides methods for identifying compounds that mediate proteasome localization and/or polypeptide degradation. The invention also provides research tools for the study of protein function.

Influence of dispersity on the activity, selectivity, and stability of Raney-Nickel catalyst during the hydrogenation of 1,4-butynediol into 1,4-butanediol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusina, S.V.; Litvin, E.F.; Kheifets, V.I.

Raney-nickel catalysts are widely used in the hydrogenation of 1,4-butynediol into 1,4-butanediol, an important intermediate for the preparation of thermostable resins, plasticizers, pharmaceutical preparations, and other compounds. The authors carried out the investigation of the influence of the dispersity of the Raney-nickel catalysts on their activity, selectivity, and stability in the hydrogenation reaction of 1,4-butynediol into 1,4-butanediol.

Apple Pomace as Potential Source of Natural Active Compounds.

PubMed

Waldbauer, Katharina; McKinnon, Ruxandra; Kopp, Brigitte

2017-08-01

Apple pomace is a waste product of the apple manufacturing industry that has been in the focus of life sciences as it represents a low-cost source of fruit-derived compounds. High fruit consumption is associated with beneficial health effects, and therefore, apple pomace and its constituents raise therapeutic interest. The present work reviews (i) the chemical constituents of apple pomace, (ii) optimized extraction methods of apple pomace compounds, and (iii) biological activities of apple pomace. Current evidence of apple pomace influence on digestion and metabolism, cholesterol and triglyceride homeostasis, diabetes, and sex hormones is summarized. Furthermore, studies regarding its antioxidative, anti-inflammatory, antiproliferative, antibacterial and antiviral effects are presented. The review concludes that apple pomace is an underutilized waste product of the apple industry with the potential of being processed for its nutritional and pharmaceutical value. Georg Thieme Verlag KG Stuttgart · New York.

Synthesis, structurale elucidation and antioxidant study of Ortho-substituted N,N’-bis(benzamidothiocarbonyl)hydrazine derivatives

NASA Astrophysics Data System (ADS)

Firdausiah, Syadza; Hasbullah, S. A.; Yamin, B. M.

2018-03-01

Some bis(thiourea) compounds have been reported to posses excellent performance in pharmaceutical and environmental fields because of their ability to form chelating complexes with various anions and metal ions. Structurally for carbonyl thiourea derivatives, to become a chelating agent, it must adopt cis-configuration. In the present study, four new bis(thiourea) derivatives namely N,N’-bis(o-fluorobenzamidothiocarbonyl)hydrazine (1), N,N’- bis(o-chloro-benzamidothiocarbonyl)hydrazine (2), N,N’-bis(o-nitrobenzamidothiocarbonyl)-hydrazine (3), and N,N’-bis(o-methylbenzamidothiocarbonyl)hydrazine (4) were successfully synthesized and characterized by CHNS microelemental analysis, FTIR, UV-Vis, and 1H and 13C NMR spectroscopy. However chemical crystallography study showed that both thiourea moieties in compound (2) and (3) adopt trans geometry. Therefore they are potential monodentate ligand with two active moieties. DPPH radical scavenging experiment showed that compound (1), (2), and (4) exhibited higher antioxidant activity than ascorbic acid (Vitamin C).

Novel benzofuran-3-one indole inhibitors of PI3 kinase-alpha and the mammalian target of rapamycin: hit to lead studies.

PubMed

Bursavich, Matthew G; Brooijmans, Natasja; Feldberg, Lawrence; Hollander, Irwin; Kim, Stephen; Lombardi, Sabrina; Park, Kaapjoo; Mallon, Robert; Gilbert, Adam M

2010-04-15

A series of benzofuran-3-one indole phosphatidylinositol-3-kinases (PI3K) inhibitors identified via HTS has been prepared. The optimized inhibitors possess single digit nanomolar activity against p110alpha (PI3K-alpha), good pharmaceutical properties, selectivity versus p110gamma (PI3K-gamma), and tunable selectivity versus the mammalian target of rapamycin (mTOR). Modeling of compounds 9 and 32 in homology models of PI3K-alpha and mTOR supports the proposed rationale for selectivity. Compounds show activity in multiple cellular proliferation assays with signaling through the PI3K pathway confirmed via phospho-Akt inhibition in PC-3 cells. Copyright 2010 Elsevier Ltd. All rights reserved.

Effects of medicinal compounds on the differentiation of the eukaryotic microorganism dictyostelium discoideum: can this model be used as a screening test for reproductive toxicity in humans?

PubMed

Dannat, K; Tillner, J; Winckler, T; Weiss, M; Eger, K; Dingermann, T

2003-03-01

Dictyostelium discoideum is a single-cell, eukaryotic microorganism that can undergo multicellular development in order to produce dormant spores. We investigated the capacity of D. discoideum to be used as a rapid screening system for potential developmental toxicity of compounds under development as pharmaceuticals. We used a set of four transgenic D. discoideum strains that expressed a reporter gene under the control of promoters that are active at certain time periods and in distinct cell types during D. discoideum development. We found that teratogens such as valproic acid, tretinoin, or thalidomide interfered to various extents with D. discoideum development, and had different effects on prestalk and prespore cell-specific reporter gene expression. Phenytoin was inactive in this assay, which may point to limitations in metabolization of the compound in Dictyostelium required to exert developmental toxicity. D. discoideum cell culture is cheap and easy to handle compared to mammalian cell cultures or animal teratogenicity models. Although the Dictyostelium-based assay described in this report may not securely predict the teratogenic potential of these drugs in humans, this organism may be qualified for rapid large-scale screenings of synthetic compounds under development as new pharmaceuticals for their potential to interfere with developmental processes and thus help to reduce the amount of teratogenicity tests in animal models.

Antifungal activity improved by coproduction of cyclodextrins and anabaenolysins in Cyanobacteria

PubMed Central

Shishido, Tania K.; Jokela, Jouni; Kolehmainen, Clara-Theresia; Fewer, David P.; Wahlsten, Matti; Wang, Hao; Rouhiainen, Leo; Rizzi, Ermanno; De Bellis, Gianluca; Permi, Perttu; Sivonen, Kaarina

2015-01-01

Cyclodextrins are cyclic oligosaccharides widely used in the pharmaceutical industry to improve drug delivery and to increase the solubility of hydrophobic compounds. Anabaenolysins are lipopeptides produced by cyanobacteria with potent lytic activity in cholesterol-containing membranes. Here, we identified the 23- to 24-kb gene clusters responsible for the production of the lipopeptide anabaenolysin. The hybrid nonribosomal peptide synthetase and polyketide synthase biosynthetic gene cluster is encoded in the genomes of three anabaenolysin-producing strains of Anabaena. We detected previously unidentified strains producing known anabaenolysins A and B and discovered the production of new variants of anabaenolysins C and D. Bioassays demonstrated that anabaenolysins have weak antifungal activity against Candida albicans. Surprisingly, addition of the hydrophilic fraction of the whole-cell extracts increased the antifungal activity of the hydrophobic anabaenolysins. The fraction contained compounds identified by NMR as α-, β-, and γ-cyclodextrins, which undergo acetylation. Cyclodextrins have been used for decades to improve the solubility and bioavailability of many drugs including antifungal compounds. This study shows a natural example of cyclodextrins improving the solubility and efficacy of an antifungal compound in an ancient lineage of photosynthetic bacteria. PMID:26474830

Monoalkylated barbiturate derivatives: X-ray crystal structure, theoretical studies, and biological activities

NASA Astrophysics Data System (ADS)

Barakat, Assem; Al-Majid, Abdullah Mohammed; Soliman, Saied M.; Islam, Mohammad Shahidul; Ghawas, Hussain Mansur; Yousuf, Sammer; Choudhary, M. Iqbal; Wadood, Abdul

2017-08-01

Barbiturate derivatives are privileged structures with a broad range of pharmaceutical applications. We prepared a series of 5-monoalkylated barbiturate derivatives (3a-l) and evaluated, in vitro, their antioxidant (DPPH assay), and α-glucosidase inhibitory activities. Compounds 3a-l were synthesized via Michael addition. The structure of compound 3k was determined using X-ray single-crystal diffraction, and geometric parameters were calculated using density functional theory at the B3LYP/6-311G(d,p) level of theory. Further, the structural analysis of 3k were also investigated. Biological studies revealed that compounds 3b (IC50 = 133.1 ± 3.2 μM), 3d (IC50 = 305 ± 7.7 μM), and 3e (IC50 = 184 ± 2.3 μM) have potent α-glucosidase enzyme inhibitors and showed greater activity than the standard drug acarbose (IC50 = 841 ± 1.73 μM). Compounds 3a-3i were found to show weak antioxidant activity against 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals (IC50 = 91 ± 0.75 to 122 ± 1.0 μM) when tested against a standard antioxidant, gallic acid (IC50 = 23 ± 0.43 μM).

Antioxidant compounds, antioxidant activity and phenolic content in peel from three tropical fruits from Yucatan, Mexico.

PubMed

Moo-Huchin, Víctor M; Moo-Huchin, Mariela I; Estrada-León, Raciel J; Cuevas-Glory, Luis; Estrada-Mota, Iván A; Ortiz-Vázquez, Elizabeth; Betancur-Ancona, David; Sauri-Duch, Enrique

2015-01-01

The aim of this study was to determine the antioxidant compounds, antioxidant activity and content of individual phenolic compounds of freeze-dried peel from three tropical fruits grown in Yucatan, México: purple star apple (Chrysophyllum cainito L.), yellow cashew and red cashew (Anacardium occidentale). The freeze-dried peels were good source of antioxidant compounds. ABTS and DPPH values in the peel from each fruit were 3050.95-3322.31 μM Trolox/100g dry weight (DW) or 890.19-970.01 mg of vitamin C/100 g DW, and 1579.04-1680.90 μM Trolox/100 g DW or 340.18-362.18 mg of vitamin C/100 g DW, respectively. Six phenolic compounds were identified in the peel from the tropical fruits studied: ferulic, caffeic, sinapic, gallic, ellagic and myricetin. This study demonstrated that freeze-dried peels from purple star apple, yellow cashew and red cashew, could serve as potential sources of antioxidants for use in food and pharmaceutical industries. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impacts of compound properties and sediment characteristics on the sorption behaviour of pharmaceuticals in aquatic systems.

PubMed

Al-Khazrajy, Omar S A; Boxall, Alistair B A

2016-11-05

Sorption is a key factor in determining the persistence, attenuation and bioavailability of sediment-associated contaminants. However, our understanding of the sorption behaviour of pharmaceuticals in sediments is poor. In this study, we investigated the sorption behaviour of a diverse set of pharmaceuticals in a range sediment types. Sorption affinity of pharmaceuticals for all sediments was found to increase in the order mefenamic acid

Determination of human-use pharmaceuticals in filtered water by direct aqueous injection: high-performance liquid chromatography/tandem mass spectrometry

USGS Publications Warehouse

Furlong, Edward T.; Noriega, Mary C.; Kanagy, Christopher J.; Kanagy, Leslie K.; Coffey, Laura J.; Burkhardt, Mark R.

2014-01-01

This report describes a method for the determination of 110 human-use pharmaceuticals using a 100-microliter aliquot of a filtered water sample directly injected into a high-performance liquid chromatograph coupled to a triple-quadrupole tandem mass spectrometer using an electrospray ionization source operated in the positive ion mode. The pharmaceuticals were separated by using a reversed-phase gradient of formic acid/ammonium formate-modified water and methanol. Multiple reaction monitoring of two fragmentations of the protonated molecular ion of each pharmaceutical to two unique product ions was used to identify each pharmaceutical qualitatively. The primary multiple reaction monitoring precursor-product ion transition was quantified for each pharmaceutical relative to the primary multiple reaction monitoring precursor-product transition of one of 19 isotope-dilution standard pharmaceuticals or the pesticide atrazine, using an exact stable isotope analogue where possible. Each isotope-dilution standard was selected, when possible, for its chemical similarity to the unlabeled pharmaceutical of interest, and added to the sample after filtration but prior to analysis. Method performance for each pharmaceutical was determined for reagent water, groundwater, treated drinking water, surface water, treated wastewater effluent, and wastewater influent sample matrixes that this method will likely be applied to. Each matrix was evaluated in order of increasing complexity to demonstrate (1) the sensitivity of the method in different water matrixes and (2) the effect of sample matrix, particularly matrix enhancement or suppression of the precursor ion signal, on the quantitative determination of pharmaceutical concentrations. Recovery of water samples spiked (fortified) with the suite of pharmaceuticals determined by this method typically was greater than 90 percent in reagent water, groundwater, drinking water, and surface water. Correction for ambient environmental concentrations of pharmaceuticals hampered the determination of absolute recoveries and method sensitivity of some compounds in some water types, particularly for wastewater effluent and influent samples. The method detection limit of each pharmaceutical was determined from analysis of pharmaceuticals fortified at multiple concentrations in reagent water. The calibration range for each compound typically spanned three orders of magnitude of concentration. Absolute sensitivity for some compounds, using isotope-dilution quantitation, ranged from 0.45 to 94.1 nanograms per liter, primarily as a result of the inherent ionization efficiency of each pharmaceutical in the electrospray ionization process. Holding-time studies indicate that acceptable recoveries of pharmaceuticals can be obtained from filtered water samples held at 4 °C for as long as 9 days after sample collection. Freezing samples to provide for storage for longer periods currently (2014) is under evaluation by the National Water Quality Laboratory.

Active pharmaceutical ingredients available as substances for extemporaneous preparation in veterinary medicine in the Czech Republic.

PubMed

Sklenář, Zbyněk; Horáčková, Kateřina; Bakhouche, Hana

2014-04-01

In veterinary medicine, extemporaneously prepared drugs can be also used in therapy. In the recent four years the selection of suitable compounds for extemporaneous (magistral) preparation has been expanded and new possibilities for the creation of formulas have appeared. The paper reports on the substances available for compounding that can be used in veterinary medicine, in the pharmacotherapeutic classes antibiotics, antimycotics, antiseptics, corticosteroids, emollients and epithelizing agents, anti-inflammatory drugs, local anesthetics, decongestives, beta-blockers and calcium channel blockers, antiemetics and prokinetics, sedatives and hypnotics. The emphasis has been placed on newly available substances. Examples of suitable magistral formulas are presented that can replace mass-produced drug products which are not readily obtainable. The aim of the paper is to inform pharmacists and veterinarians about new possibilities of drug compounding. compounded preparations extemporaneous preparation compounding of drugs possibilities magistral formulas in veterinary medicine.

Molecular Mechanism of Selectivity among G Protein-Coupled Receptor Kinase 2 Inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thal, David M.; Yeow, Raymond Y.; Schoenau, Christian

2012-07-11

G protein-coupled receptors (GPCRs) are key regulators of cell physiology and control processes ranging from glucose homeostasis to contractility of the heart. A major mechanism for the desensitization of activated GPCRs is their phosphorylation by GPCR kinases (GRKs). Overexpression of GRK2 is strongly linked to heart failure, and GRK2 has long been considered a pharmaceutical target for the treatment of cardiovascular disease. Several lead compounds developed by Takeda Pharmaceuticals show high selectivity for GRK2 and therapeutic potential for the treatment of heart failure. To understand how these drugs achieve their selectivity, we determined crystal structures of the bovine GRK2-G{beta}{gamma} complexmore » in the presence of two of these inhibitors. Comparison with the apoGRK2-G{beta}{gamma} structure demonstrates that the compounds bind in the kinase active site in a manner similar to that of the AGC kinase inhibitor balanol. Both balanol and the Takeda compounds induce a slight closure of the kinase domain, the degree of which correlates with the potencies of the inhibitors. Based on our crystal structures and homology modeling, we identified five amino acids surrounding the inhibitor binding site that we hypothesized could contribute to inhibitor selectivity. However, our results indicate that these residues are not major determinants of selectivity among GRK subfamilies. Rather, selectivity is achieved by the stabilization of a unique inactive conformation of the GRK2 kinase domain.« less

Synthesis, Structural Characterization and Antinociceptive Activities of New Arylated Quinolines via Suzuki-Miyaura Cross Coupling Reaction.

PubMed

Ullah, Malik A; Adeel, Muhammad; Tahir, Muhammad N; Rauf, Abdur; Akram, Muhammad; Hadda, Taibi B; Mabkhot, Yahia N; Muhammad, Naveed; Naseer, Fehmida; Mubarak, Mohammad S

2017-01-01

The quinoline ring system is one of the most commonly encountered heterocycles in medicinal chemistry, due to the pharmaceutical and medicinal uses of derivatives containing this ring. These quinoline-based compounds have remarkable biological activity, as they are employed as antimalarial, antibacterial, antifungal, and antitumor agents. The quinoline nucleus can be synthesized by various traditional methods such as the Skraup reaction, Friedlaender synthesis, Combes quinoline synthesis, Larock quinoline synthesis, among others. The aim of the present work is to synthesize a number of new arylated quninolines having significant antinoceciptive effect through the Suzuki-Miyaura cross coupling reaction using 3- bromoquinoline as a starting material. A number of new quinoline derivatives have been synthesized. Structures of the newly synthesized compounds were confirmed by means of IR, NMR, and mass spectrometry, and by elemental analysis. In addition, the molecular structures of two representative derivatives were determined with the aid of X-ray crystallography. Additionally, the antinociceptive activity of the prepared compounds was evaluated in vivo; results revealed that most of the tested compounds exhibited a dosedependent antinociceptive effect. Prepared compounds were found to exhibit significant antinociceptive activities and could be used as potential analgesic agents. Further work, however, may be required to establish the safety and efficacy of these compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Occurrence of pharmaceutical compounds in wastewater process streams in Dublin, Ireland.

PubMed

Lacey, Clair; Basha, Shaik; Morrissey, Anne; Tobin, John M

2012-01-01

The aim of this work is to establish baseline levels of pharmaceuticals in three wastewater treatment plant (WWTP) streams in the greater Dublin region to assess the removal efficiency of the selected WWTPs and to investigate the existence of any seasonal variability. Twenty compounds including several classes of antibiotics, acidic and basic pharmaceuticals, and prescribed medications were selected for investigation using a combination of membrane filtration, solid phase extraction (SPE) cleanup, and liquid chromatography-electrospray ionization tandem mass spectrometry. Fourteen of the selected compounds were found in the samples. Increased effluent concentrations, compared to influent concentrations, for a number of compounds (carbamazepine, clotrimazole, propranolol, nimesulide, furosemide, mefenamic acid, diclofenac, metoprolol, and gemfibrozil) were observed. The detected concentrations were generally below toxicity levels and based on current knowledge are unlikely to pose any threat to aquatic species. Mefenamic acid concentrations detected in both Leixlip and Swords effluents may potentially exert ecotoxicological effects with maximum risk quotients (i.e., ratio of predicted exposure concentration to predicted no effect concentration) of 4.04 and 1.33, respectively.

Two-year survey of specific hospital wastewater treatment and its impact on pharmaceutical discharges.

PubMed

Wiest, Laure; Chonova, Teofana; Bergé, Alexandre; Baudot, Robert; Bessueille-Barbier, Frédérique; Ayouni-Derouiche, Linda; Vulliet, Emmanuelle

2018-04-01

It is well known that pharmaceuticals are not completely removed by conventional activated sludge wastewater treatment plants. Hospital effluents are of major concern, as they present high concentrations of pharmaceutically active compounds. Despite this, these specific effluents are usually co-treated with domestic wastewaters. Separate treatment has been recommended. However, there is a lack of information concerning the efficiency of separate hospital wastewater treatment by activated sludge, especially on the removal of pharmaceuticals. In this context, this article presents the results of a 2-year monitoring of conventional parameters, surfactants, gadolinium, and 13 pharmaceuticals on the specific study site SIPIBEL. This site allows the characterization of urban and hospital wastewaters and their separate treatment using the same process. Flow proportional sampling, solid-phase extraction, and liquid chromatography coupled with tandem mass spectrometry were used in order to obtain accurate data and limits of quantification consistent with ultra-trace detection. Thanks to these consolidated data, an in-depth characterization of urban and hospital wastewaters was realized, as well as a comparison of treatment efficiency between both effluents. Higher concentrations of organic carbon, AOX, phosphates, gadolinium, paracetamol, ketoprofen, and antibiotics were observed in hospital wastewaters compared to urban wastewaters. Globally higher removals were observed in the hospital wastewater treatment plant, and some parameters were shown to be of high importance regarding removal efficiencies: hydraulic retention time, redox conditions, and ambient temperature. Eleven pharmaceuticals were still quantified at relevant concentrations in hospital and urban wastewaters after treatment (e.g., up to 1 μg/L for sulfamethoxazole). However, as the urban flow was about 37 times higher than the hospital flow, the hospital contribution appeared relatively low compared to domestic discharges. Thanks to the SIPIBEL site, data obtained from this 2-year program are useful to evaluate the relevance of separate hospital wastewater treatment.

Pharmaceutical grey water footprint: Accounting, influence of wastewater treatment plants and implications of the reuse.

PubMed

Martínez-Alcalá, Isabel; Pellicer-Martínez, Francisco; Fernández-López, Carmen

2018-05-15

Emerging pollutants, including pharmaceutical compounds, are producing water pollution problems around the world. Some pharmaceutical pollutants, which mainly reach ecosystems within wastewater discharges, are persistent in the water cycle and can also reach the food chain. This work addresses this issue, accounting the grey component of the water footprint (GWF P ) for four of the most common pharmaceutical compounds (carbamazepine (CBZ), diclofenac (DCF), ketoprofen (KTP) and naproxen (NPX)). In addition, the GWF C for the main conventional pollutants is also accounted (nitrate, phosphates and organic matter). The case study is the Murcia Region of southeastern Spain, where wastewater treatment plants (WWTPs) purify 99.1% of the wastewater discharges and there is an important direct reuse of the treated wastewater in irrigation. Thus, the influence of WWTPs and reuse on the GWF is analysed. The results reveal that GWF P , only taking into account pharmaceutical pollutants, has a value of 301 m 3 inhabitant -1 year -1 ; considering only conventional pollutants (GWF C ), this value increases to 4718 m 3 inhabitant -1 year -1 . So, the difference between these values is such that in other areas with consumption habits similar to those of the Murcia Region, and without wastewater purification, conventional pollutants may well establish the value of the GWF. On average, the WWTPs reduce the GWF C by 90% and the GWF P by 26%. These different reductions of the pollutant concentrations in the treated effluents show that the GWF is not only due to conventional pollutants, and other contaminants can became critical, such as the pharmaceutical pollutants. The reuse further reduces the value of the GWF for the Murcia Region, by around 43.6%. However, the reuse of treated wastewater is controversial, considering the pharmaceutical contaminants and their possible consequences in the food chain. In these cases, the GWF of pharmaceutical pollutants can be used to provide a first approximation of the dilution that should be applied to the treated wastewater discharges when they are reused for another economic activity that imposes quality restrictions. For the case of agriculture in the Murcia Region, the dilution required is 2 (fresh water) to 1 (treated wastewater), taking into account the pollution thresholds established in this work. Copyright © 2018 Elsevier Ltd. All rights reserved.

Colloids as a sink for certain pharmaceuticals in the aquatic environment.

PubMed

Maskaoui, Khalid; Zhou, John L

2010-05-01

The occurrence and fate of pharmaceuticals in the aquatic environment is recognized as one of the emerging issues in environmental chemistry and as a matter of public concern. Existing data tend to focus on the concentrations of pharmaceuticals in the aqueous phase, with limited studies on their concentrations in particulate phase such as sediments. Furthermore, current water quality monitoring does not differentiate between soluble and colloidal phases in water samples, hindering our understanding of the bioavailability and bioaccumulation of pharmaceuticals in aquatic organisms. In this study, an investigation was conducted into the concentrations and phase association (soluble, colloidal, suspended particulate matter or SPM) of selected pharmaceuticals (propranolol, sulfamethoxazole, meberverine, thioridazine, carbamazepine, tamoxifen, indomethacine, diclofenac, and meclofenamic acid) in river water, effluents from sewage treatment works (STW), and groundwater in the UK. The occurrence and phase association of selected pharmaceuticals propranolol, sulfamethoxazole, meberverine, thioridazine, carbamazepine, tamoxifen, indomethacine, diclofenac, and meclofenamic acid in contrasting aquatic environments (river, sewage effluent, and groundwater) were studied. Colloids were isolated by cross-flow ultrafiltration (CFUF). Water samples were extracted by solid-phase extraction (SPE), while SPM was extracted by microwave. All sample extracts were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the multiple reaction monitoring. Five compounds propranolol, sulfamethoxazole, carbamazepine, indomethacine, and diclofenac were detected in all samples, with carbamazepine showing the highest concentrations in all phases. The highest concentrations of these compounds were detected in STW effluents, confirming STW as a key source of these compounds in the aquatic environments. The calculation of partition coefficients of pharmaceuticals between SPM and filtrate (observed partition coefficients, Kobsp, Kobsoc), between SPM and soluble phase (intrinsic partition coefficients, Kintp, Kintoc), and between colloids and soluble phase (Kcoc) showed that intrinsic partition coefficients (Kintp, Kintoc) are between 25% and 96%, and between 18% and 82% higher than relevant observed partition coefficients values, and are much less variable. Secondly, Kcoc values are 3-4 orders of magnitude greater than Kintoc values, indicating that aquatic colloids are substantially more powerful sorbents for accumulating pharmaceuticals than sediments. Furthermore, mass balance calculations of pharmaceutical concentrations demonstrate that between 23% and 70% of propranolol, 17-62% of sulfamethoxazole, 7-58% of carbamazepine, 19-84% of indomethacine, and 9-74% of diclofenac are present in the colloidal phase. The results provide direct evidence that sorption to colloids provides an important sink for the pharmaceuticals in the aquatic environment. Such strong pharmaceutical/colloid interactions may provide a long-term storage of pharmaceuticals, hence, increasing their persistence while reducing their bioavailability in the environment. Pharmaceutical compounds have been detected not only in the aqueous phase but also in suspended particles; it is important, therefore, to have a holistic approach in future environmental fate investigation of pharmaceuticals. For example, more research is needed to assess the storage and long-term record of pharmaceutical residues in aquatic sediments by which benthic organisms will be most affected. Aquatic colloids have been shown to account for the accumulation of major fractions of total pharmaceutical concentrations in the aquatic environment, demonstrating unequivocally the importance of aquatic colloids as a sink for such residues in the aquatic systems. As aquatic colloids are abundant, ubiquitous, and highly powerful sorbents, they are expected to influence the bioavailability and bioaccumulation of such chemicals by aquatic organisms. It is therefore critical for colloids to be incorporated into water quality models for prediction and risk assessment purposes.

Occurrence of acidic pharmaceuticals in raw and treated sewages and in receiving waters.

PubMed

Lindqvist, Niina; Tuhkanen, Tuula; Kronberg, Leif

2005-06-01

The occurrence of five acidic pharmaceuticals, ibuprofen, naproxen, ketoprofen, diclofenac and bezafibrate, in seven different sewage treatment plants (STP) and three receiving waters were determined. The analytical procedure included solid phase extraction, liquid chromatographic separation and detection by a triple-quadrupole mass spectrometer. The studied pharmaceuticals were found in all the STPs. The pattern of the occurrence of individual compounds was the same in every STP and matched the consumption figures reported in the literature. Ibuprofen is the most used pharmaceutical in Finland and was accordingly found to be the most abundant compound in the raw sewage. In the treatment processes, the highest removal rate was observed for ibuprofen and the lowest for diclofenac, 92%+/-8% and 26%+/-17%, respectively. Due to the incomplete removal in the STPs, the pharmaceuticals were found in rivers at the discharge points of the STP effluents. Downstream from the discharge points, the concentrations decreased significantly mainly due to dilution in the river water. The risk to the aquatic environment was estimated by a ratio of measured environmental concentration (MEC) and predicted no-effect concentration (PNEC). At the concentrations the compounds were found in the surface waters, they should not pose risk for the aquatic environment. However, at dry seasons and/or during malfunctions of STPs, ibuprofen could be associated with a risk in small river systems.

Evaluation of pharmaceuticals removal by sewage sludge-derived adsorbents with rapid small-scale column tests

NASA Astrophysics Data System (ADS)

Zhang, P.; Ding, R.; Wallace, R.; Bandosz, T.

2015-12-01

New composite adsorbents were developed by pyrolyzing sewage sludge and fish waste (75:25 or 90:10 dry mass ratio) at 650 oC and 950 oC. Batch adsorption experiments demonstrated that the composite adsorbents were able to adsorb a wide range of organic contaminants (volatile organic compounds, pharmaceuticals and endocrine disrupting compounds (EDCs), and nitrosamine disinfection byproducts) with high capacities. Here we further examine the performance of the adsorbents for the simultaneous removal of 8 pharmaceuticals and EDCs with rapid small-scale column tests (RSSCT). Results show that the order of breakthrough in RSSCT is in general consistent with the affinity determined via batch tests. As expected, the maximum amount of adsorption for each compound obtained from RSSCT is identical to or less than that obtained from batch tests (with only one exception), due to adsorption kinetics. However, despite the very different input concentration (1 mg/L vs. 100 mg/L) and contact time (2 min empty bed contact time vs. 16 hour equilibrium time) used in RSSCT and batch tests, the maximum amount of pharmaceuticals and EDCs adsorbed under RSSCT is still about one half of that under equilibrium batch tests, validating the approach of using batch tests with much higher input concentrations to determine adsorption capacities. Results of a pilot-scale column test in a drinking water treatment plant for pharmaceuticals removal will also be presented.

Determination of pharmaceutical residues in drinking water in Poland using a new SPE-GC-MS(SIM) method based on Speedisk extraction disks and DIMETRIS derivatization.

PubMed

Caban, Magda; Lis, Ewa; Kumirska, Jolanta; Stepnowski, Piotr

2015-12-15

The presence of pharmaceuticals in drinking water, even at very low concentrations, has raised concerns among stakeholders such as drinking-water regulators, governments, water suppliers and the public, with regard to the potential risks to humans. Despite this, the occurrence and the fate of pharmaceuticals in drinking waters of many countries (e.g. in Poland) remains unknown. There is a lack of sufficiently sensitive and reliable analytical methods for such analyses and a need for more in-depth hydrogeological analysis of the possible sources of drug residues in drinking water. In this paper, a multi-residual method for the simultaneous determination of seventeen human pharmaceuticals in drinking waters has been developed. Large-volume extractions using Speedisk extraction disks, and derivatization prior to GC-MS-SIM analysis using a new silylating agent DIMETRIS were applied. The method detection limits (MDLs) ranged from 0.9 to 5.7ng/L and the absolute recoveries of the target compounds were above 80% for most analytes. The developed method was successfully applied in the analysis of the target compounds in drinking water collected in Gdansk (Poland), and of the 17 pharmaceuticals, 6 compounds were detected at least once. During the investigation, the geomorphology of the site region was taken into account, possible sources of pharmaceuticals in the analysed drinking water samples were investigated, and the presence of the drugs in ground and surface waters, raw and treated drinking waters was determined. Concentrations were also compared with those observed in other countries. As a result, this study has not only developed a new analytical method for determining pharmaceuticals in drinking waters as well as rendering missing information for Poland (a country with one of the highest consumptions of pharmaceuticals in Europe), but it also presents a modelled in-depth hydrogeological analysis of the real sources of drugs in drinking waters. Copyright © 2015 Elsevier B.V. All rights reserved.

Screening of environmental contaminants for ecdysteroid agonist and antagonist activity using the Drosophila melanogaster B(II) cell in vitro assay.

PubMed

Dinan, L; Bourne, P; Whiting, P; Dhadialla, T S; Hutchinson, T H

2001-09-01

The B(II) bioassay was developed as a rapid and reliable tool for detecting potential insect growth regulators acting as ecdysteroid receptor (ant)agonists. Based on an ecdysteroid-responsive cell line from Drosophila melanogaster, this microplate assay is ideally suited to the evaluation of environmental contaminants as potential endocrine disrupters. Data are presented for about 80 potential environmental contaminants, including industrial chemicals, pesticides, pharmaceuticals, phytoestrogens, and vertebrate steroids, and are compared with data for known (ant)agonists. Apart from androst-4-ene-3,17-dione (a weak antagonist), vertebrate steroids were inactive at concentrations up to 10(-3) M. The vast majority of xenobiotics also showed no (ant)agonist activity. Among the industrial chemicals, antagonistic activity was observed for bisphenol A median effective concentration (EC50) of 1.0 x 10(-4) M and diethylphthalate (EC50 of 2.0 x 10(-3) M). Some organochlorine compounds also showed weak antagonistic activity, including o,p'-dichlorodiphenyldichloroethylene (DDE), p,p'-DDE, dieldrin, and lindane (EC50 of 3.0 x 10(-5) M). For lindane, bisphenol A, and diethylphthalate, activity is not associated with impurities in the samples and, for lindane and bisphenol A at least, the compounds are able to compete with ecdysteroids for the ligand binding site on the receptor complex, albeit at concentrations very much higher than those found in the environment. The only pharmaceutical showing any detectable antagonist activity was 17alpha-ethynylestradiol. In the context of recent publications on potential endocrine disruption in marine and freshwater arthropods, these findings suggest that, for some compounds (e.g., diethylstilbestrol), ecdysteroid receptor-mediated responses are unlikely to be involved in producing chronic effects. The B(II) assay has a potentially valuable role to play in distinguishing between endocrine-mediated, which normally occur at submicromolar concentrations, and pharmacological effects in insects and crustaceans.

Pharmaceuticals' sorptions relative to properties of thirteen different soils.

PubMed

Kodešová, Radka; Grabic, Roman; Kočárek, Martin; Klement, Aleš; Golovko, Oksana; Fér, Miroslav; Nikodem, Antonín; Jakšík, Ondřej

2015-04-01

Transport of human and veterinary pharmaceuticals in soils and consequent ground-water contamination are influenced by many factors, including compound sorption on soil particles. Here we evaluate the sorption isotherms for 7 pharmaceuticals on 13 soils, described by Freundlich equations, and assess the impact of soil properties on various pharmaceuticals' sorption on soils. Sorption of ionizable pharmaceuticals was, in many cases, highly affected by soil pH. The sorption coefficient of sulfamethoxazole was negatively correlated to soil pH, and thus positively related to hydrolytic acidity and exchangeable acidity. Sorption coefficients for clindamycin and clarithromycin were positively related to soil pH and thus negatively related to hydrolytic acidity and exchangeable acidity, and positively related to base cation saturation. The sorption coefficients for the remaining pharmaceuticals (trimethoprim, metoprolol, atenolol, and carbamazepine) were also positively correlated with the base cation saturation and cation exchange capacity. Positive correlations between sorption coefficients and clay content were found for clindamycin, clarithromycin, atenolol, and metoprolol. Positive correlations between sorption coefficients and organic carbon content were obtained for trimethoprim and carbamazepine. Pedotransfer rules for predicting sorption coefficients of various pharmaceuticals included hydrolytic acidity (sulfamethoxazole), organic carbon content (trimethoprimand carbamazepine), base cation saturation (atenolol and metoprolol), exchangeable acidity and clay content (clindamycin), and soil active pH and clay content (clarithromycin). Pedotransfer rules, predicting the Freundlich sorption coefficients, could be applied for prediction of pharmaceutical mobility in soils with similar soil properties. Predicted sorption coefficients together with pharmaceutical half-lives and other imputes (e.g., soil-hydraulic, geological, hydro-geological, climatic) may be used for assessing potential ground-water contamination. Copyright © 2014 Elsevier B.V. All rights reserved.

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

PubMed Central

2015-01-01

Summary The implementation of continuous flow processing as a key enabling technology has transformed the way we conduct chemistry and has expanded our synthetic capabilities. As a result many new preparative routes have been designed towards commercially relevant drug compounds achieving more efficient and reproducible manufacture. This review article aims to illustrate the holistic systems approach and diverse applications of flow chemistry to the preparation of pharmaceutically active molecules, demonstrating the value of this strategy towards every aspect ranging from synthesis, in-line analysis and purification to final formulation and tableting. Although this review will primarily concentrate on large scale continuous processing, additional selected syntheses using micro or meso-scaled flow reactors will be exemplified for key transformations and process control. It is hoped that the reader will gain an appreciation of the innovative technology and transformational nature that flow chemistry can leverage to an overall process. PMID:26425178

Recent Advances in Lipase-Mediated Preparation of Pharmaceuticals and Their Intermediates

PubMed Central

Carvalho, Ana Caroline Lustosa de Melo; Fonseca, Thiago de Sousa; de Mattos, Marcos Carlos; de Oliveira, Maria da Conceição Ferreira; de Lemos, Telma Leda Gomes; Molinari, Francesco; Romano, Diego; Serra, Immacolata

2015-01-01

Biocatalysis offers an alternative approach to conventional chemical processes for the production of single-isomer chiral drugs. Lipases are one of the most used enzymes in the synthesis of enantiomerically pure intermediates. The use of this type of enzyme is mainly due to the characteristics of their regio-, chemo- and enantioselectivity in the resolution process of racemates, without the use of cofactors. Moreover, this class of enzymes has generally excellent stability in the presence of organic solvents, facilitating the solubility of the organic substrate to be modified. Further improvements and new applications have been achieved in the syntheses of biologically active compounds catalyzed by lipases. This review critically reports and discusses examples from recent literature (2007 to mid-2015), concerning the synthesis of enantiomerically pure active pharmaceutical ingredients (APIs) and their intermediates in which the key step involves the action of a lipase. PMID:26690428

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry.

PubMed

Baumann, Marcus; Baxendale, Ian R

2015-01-01

The implementation of continuous flow processing as a key enabling technology has transformed the way we conduct chemistry and has expanded our synthetic capabilities. As a result many new preparative routes have been designed towards commercially relevant drug compounds achieving more efficient and reproducible manufacture. This review article aims to illustrate the holistic systems approach and diverse applications of flow chemistry to the preparation of pharmaceutically active molecules, demonstrating the value of this strategy towards every aspect ranging from synthesis, in-line analysis and purification to final formulation and tableting. Although this review will primarily concentrate on large scale continuous processing, additional selected syntheses using micro or meso-scaled flow reactors will be exemplified for key transformations and process control. It is hoped that the reader will gain an appreciation of the innovative technology and transformational nature that flow chemistry can leverage to an overall process.

Analysis and hit filtering of a very large library of compounds screened against Mycobacterium tuberculosis.

PubMed

Ekins, Sean; Kaneko, Takushi; Lipinski, Christopher A; Bradford, Justin; Dole, Krishna; Spektor, Anna; Gregory, Kellan; Blondeau, David; Ernst, Sylvia; Yang, Jeremy; Goncharoff, Nicko; Hohman, Moses M; Bunin, Barry A

2010-11-01

There is an urgent need for new drugs against tuberculosis which annually claims 1.7-1.8 million lives. One approach to identify potential leads is to screen in vitro small molecules against Mycobacterium tuberculosis (Mtb). Until recently there was no central repository to collect information on compounds screened. Consequently, it has been difficult to analyze molecular properties of compounds that inhibit the growth of Mtb in vitro. We have collected data from publically available sources on over 300 000 small molecules deposited in the Collaborative Drug Discovery TB Database. A cheminformatics analysis on these compounds indicates that inhibitors of the growth of Mtb have statistically higher mean logP, rule of 5 alerts, while also having lower HBD count, atom count and lower PSA (ChemAxon descriptors), compared to compounds that are classed as inactive. Additionally, Bayesian models for selecting Mtb active compounds were evaluated with over 100 000 compounds and, they demonstrated 10 fold enrichment over random for the top ranked 600 compounds. This represents a promising approach for finding compounds active against Mtb in whole cells screened under the same in vitro conditions. Various sets of Mtb hit molecules were also examined by various filtering rules used widely in the pharmaceutical industry to identify compounds with potentially reactive moieties. We found differences between the number of compounds flagged by these rules in Mtb datasets, malaria hits, FDA approved drugs and antibiotics. Combining these approaches may enable selection of compounds with increased probability of inhibition of whole cell Mtb activity.

Pharmaceuticals in on-site sewage effluent and ground water, Western Montana

USGS Publications Warehouse

Godfrey, E.; Woessner, W.W.; Benotti, M.J.

2007-01-01

Human use of pharmaceuticals results in the excretion and disposal of compounds that become part of municipal and domestic waste streams. On-site waste water disposal and leaking city sewer systems can provide avenues for the migration of effluent to the underlying aquifers. This research assessed the occurrence and persistence of 22 target pharmaceuticals in septic tank effluent and two shallow, coarse-grained aquifers in western Montana. Twelve compounds (acetaminophen, caffeine, codeine, carbamazepine, cotinine, erythromycin-18, nicotine, paraxanthine, ranitidine, sulfamethoxazole, trimethoprim, and warfarin) were detected in a high school septic tank effluent. Three of the 12 compounds, carbamazepine, sulfamethoxazole, and nicotine, were detected in the underlying sand and gravel aquifer after effluent percolation through a 2.0-m thick sand vadose zone. Sampling of a second sand, gravel, and cobble dominated unconfined aquifer, partially overlain by septic systems and a city sewer system, revealed the presence of caffeine, carbamazepine, cotinine, nicotine, and trimethoprim. The presence of carbamazepine and sulfamethoxazole in these aquifers appears to correlate with local usage based on a reported monthly prescription volume. This work highlights the need for expanding geochemical investigations of sewage waste impacted ground water systems to include sampling for selected pharmaceuticals. ?? 2007 National Ground Water Association.

Pharmaceuticals in on-site sewage effluent and ground water, Western Montana.

PubMed

Godfrey, Emily; Woessner, William W; Benotti, Mark J

2007-01-01

Human use of pharmaceuticals results in the excretion and disposal of compounds that become part of municipal and domestic waste streams. On-site waste water disposal and leaking city sewer systems can provide avenues for the migration of effluent to the underlying aquifers. This research assessed the occurrence and persistence of 22 target pharmaceuticals in septic tank effluent and two shallow, coarse-grained aquifers in western Montana. Twelve compounds (acetaminophen, caffeine, codeine, carbamazepine, cotinine, erythromycin-18, nicotine, paraxanthine, ranitidine, sulfamethoxazole, trimethoprim, and warfarin) were detected in a high school septic tank effluent. Three of the 12 compounds, carbamazepine, sulfamethoxazole, and nicotine, were detected in the underlying sand and gravel aquifer after effluent percolation through a 2.0-m thick sand vadose zone. Sampling of a second sand, gravel, and cobble dominated unconfined aquifer, partially overlain by septic systems and a city sewer system, revealed the presence of caffeine, carbamazepine, cotinine, nicotine, and trimethoprim. The presence of carbamazepine and sulfamethoxazole in these aquifers appears to correlate with local usage based on a reported monthly prescription volume. This work highlights the need for expanding geochemical investigations of sewage waste impacted ground water systems to include sampling for selected pharmaceuticals.

Fate of pharmaceutical compounds in hydroponic mesocosms planted with Scirpus validus.

PubMed

Zhang, Dong Qing; Gersberg, Richard M; Hua, Tao; Zhu, Junfei; Goyal, Manish Kumar; Ng, Wun Jern; Tan, Soon Keat

2013-10-01

A systematic approach to assess the fate of selected pharmaceuticals (carbamazepine, naproxen, diclofenac, clofibric acid and caffeine) in hydroponic mesocosms is described. The overall objective was to determine the kinetics of depletion (from solution) and plant uptake for these compounds in mesocosms planted with S. validus growing hydroponically. The potential for translocation of these pharmaceuticals from the roots to the shoots was also assessed. After 21 days of incubation, nearly all of the caffeine, naproxen and diclofenac were eliminated from solution, whereas carbamazepine and clofibric acid were recalcitrant to both photodegradation and biodegradation. The fact that the BAFs for roots for carbamazepine and clofibric acid were greater than 5, while the BAFs for naproxen, diclofenac and caffeine were less than 5, implied that the latter two compounds although recalcitrant to biodegradation, still had relatively high potential for plant uptake. Naproxen was sensitive to both photodegradation (30-42%) and biodegradation (>50%), while diclofenac was particularly sensitive (>70%) to photodegradation alone. No significant correlations (p > 0.05) were found between the rate constants of depletion or plant tissue levels of the pharmaceuticals and either log Kow or log Dow. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multi-residue analysis method for analysis of pharmaceuticals using liquid chromatography-time of flight/mass spectrometry (LC-TOF/MS) in water sample

NASA Astrophysics Data System (ADS)

Al-Qaim, Fouad Fadhil; Abdullah, Md Pauzi; Othman, Mohamed Rozali

2013-11-01

In this work, a developed method using solid - phase extraction (SPE) followed by liquid chromatography - time of flight mass spectrometry (LC-ESI-TOF/MS) was developed and validated for quantification and confirmation of eleven pharmaceuticals with different therapeutic classes in water samples, Malaysia. These compounds are caffeine (CAF), prazosin (PRZ), enalapril (ENL), carbamazepine (CBZ), nifedipine (NFD), levonorgestrel (LNG), simvastatin (SMV), hydrochlorothiazide (HYD), gliclazide (GLIC), diclofenac-Na (DIC-Na) and mefenamic acid (MEF). LC was performed on a Dionex Ultimate 3000/LC 09115047 (USA) system. Chromatography was performed on a Thermo Scientific C18 (250 mm × 2.1 mm, i.d.: 5μm) column. Several parameters were optimised such as; mobile phase, gradient elution, collision energy and solvent elution for extraction of compounds from water. The recoveries obtained ranged from 30-148 % in river water. Five pharmaceutical compounds were detected in the surface water samples: caffeine, prazosin, enalpril, diclofenac-Na and mefenamic acid. The developed method is precise and accepted recoveries were got. In addition, this method is suitable to identify and quantify trace concentrations of pharmaceuticals in surface water.

Quantitative on-line preconcentration-liquid chromatography coupled with tandem mass spectrometry method for the determination of pharmaceutical compounds in water.

PubMed

Idder, Salima; Ley, Laurent; Mazellier, Patrick; Budzinski, Hélène

2013-12-17

One of the current environmental issues concerns the presence and fate of pharmaceuticals in water bodies as these compounds may represent a potential environmental problem. The characterization of pharmaceutical contamination requires powerful analytical method able to quantify these pollutants at very low concentration (few ng L(-1)). In this work, a multi-residue analytical methodology (on-line solid phase extraction-liquid chromatography-triple quadrupole mass spectrometry using positive and negative electrospray ionization) has been developed and validated for 40 multi-class pharmaceuticals and metabolites for tap and surface waters. This on-line SPE method was very convenient and efficient compared to classical off-line SPE method because of its shorter total run time including sample preparation and smaller sample volume (1 mL vs up to 1 L). The optimized method included several therapeutic classes as lipid regulators, antibiotics, beta-blockers, non-steroidal anti-inflammatories, antineoplastic, etc., with various physicochemical properties. Quantification has been achieved with the internal standards. The limits of detection are between 0.7 and 15 ng L(-1) for drinking waters and 2-15 ng L(-1) for surface waters. The inter-day precision values are below 20% for each studied level. The improvement and strength of the analytical method has been verified along a monitoring of these 40 pharmaceuticals in Isle River, a French stream located in the South West of France. During this survey, 16 pharmaceutical compounds have been detected. Copyright © 2013 Elsevier B.V. All rights reserved.

Development of Safe and Effective Botanical Dietary Supplements

PubMed Central

2015-01-01

Regulated differently than drugs or foods, the market for botanical dietary supplements continues to grow worldwide. The recently implemented U.S. FDA regulation that all botanical dietary supplements must be produced using good manufacturing practice is an important step toward enhancing the safety of these products, but additional safeguards could be implemented, and unlike drugs, there are currently no efficacy requirements. To ensure a safe and effective product, botanical dietary supplements should be developed in a manner analogous to pharmaceuticals that involves identification of mechanisms of action and active constituents, chemical standardization based on the active compounds, biological standardization based on pharmacological activity, preclinical evaluation of toxicity and potential for drug–botanical interactions, metabolism of active compounds, and finally, clinical studies of safety and efficacy. Completing these steps will enable the translation of botanicals from the field to safe human use as dietary supplements. PMID:26125082

[Methodology of Screening New Antibiotics: Present Status and Prospects].

PubMed

Trenin, A S

2015-01-01

Due to extensive distribution of pathogen resistance to available pharmaceuticals and serious problems in the treatment of various infections and tumor diseases, the necessity of new antibiotics is urgent. The basic methodological approaches to chemical synthesis of antibiotics and screening of new antibiotics among natural products, mainly among microbial secondary metabolites, are considered in the review. Since the natural compounds are very much diverse, screening of such substances gives a good opportunity to discover antibiotics of various chemical structure and mechanism of action. Such an approach followed by chemical or biological transformation, is capable of providing the health care with new effective pharmaceuticals. The review is mainly concentrated on screening of natural products and methodological problems, such as: isolation of microbial producers from the habitats, cultivation of microorganisms producing appropriate substances, isolation and chemical characterization of microbial metabolites, identification of the biological activity of the metabolites. The main attention is paid to the problems of microbial secondary metabolism and design of new models for screening biologically active compounds. The last achievements in the field of antibiotics and most perspective approaches to future investigations are discussed. The main methodological approach to isolation and cultivation of the producers remains actual and needs constant improvement. The increase of the screening efficiency can be achieved by more rapid chemical identification of antibiotics and design of new screening models based on the biological activity detection.

Endocrine disruptors compounds, pharmaceuticals and personal care products in urban wastewater: implications for agricultural reuse and their removal by adsorption process.

PubMed

Grassi, Mariangela; Rizzo, Luigi; Farina, Anna

2013-06-01

In the last years, a lot of emerging contaminants, such as, endocrine disruptors compounds (EDCs), pharmaceuticals, and personal care products (PPCPs) have been detected in wastewater. Because of their toxicity and possible adverse effects on the environment and humans, their release from urban wastewater treatment plants (UWWTPs) effluents should be minimized, particularly when a wastewater reuse for crops irrigation is expected. Many processes have been investigated for advanced treatment of UWWTP effluents as well as for emerging contaminant degradation; among these, adsorption process was successfully used to remove EDCs and PPCPs from wastewater. This article shortly reviews EDCs and PPCPs removal from UWWTP effluents by adsorption process using conventional and non-conventional adsorbents. The fate of EDCs and PPCPs in UWWTPs and the implications for agricultural wastewater reuse has been addressed too. In spite of the adsorption process looking to be a valuable alternative to other advanced technologies for the removal of emerging contaminants from wastewater, some gaps still remain to evaluate the actual feasibility at full scale. However, according to a few studies available in scientific literature on the use of both powdered activated carbon and granular activated carbon at full scale, adsorption process by activated carbon is a promising, potentially effective, and economically feasible solution for producing safe wastewater for agricultural reuse.

Adsorption characteristics of selected hydrophilic and hydrophobic micropollutants in water using activated carbon.

PubMed

Nam, Seung-Woo; Choi, Dae-Jin; Kim, Seung-Kyu; Her, Namguk; Zoh, Kyung-Duk

2014-04-15

In this study, we investigated adsorption characteristics of nine selected micropollutants (six pharmaceuticals, two pesticides, and one endocrine disruptor) in water using an activated carbon. The effects of carbon dosage, contact time, pH, DOM (dissolved organic matter), and temperature on the adsorption removal of micropollutants were examined. Increasing carbon dosage and contact time enhanced the removal of micropollutants. Sorption coefficients of hydrophilic compounds (caffeine, acetaminophen, sulfamethoxazole, and sulfamethazine) fit a linear isotherm and hydrophobic compounds (naproxen, diclofenac, 2, 4-D, triclocarban, and atrazine) fit a Freundlich isotherm. The removal of hydrophobic pollutants and caffeine were independent of pH changes, but acetaminophen, sulfamethazine, and sulfamethoxazole were adsorbed by mainly electrostatic interaction with activated carbon and so were affected by pH. The decrease in adsorption removal in surface water samples was observed and this decrease was more significant for hydrophobic than hydrophilic compounds. The decline in the adsorption capacity in surface water samples is caused by the competitive inhibition of DOM with micropollutants onto activated carbon. Low temperature (5°C) also decreased the adsorption removal of micropollutants, and affected hydrophobic compounds more than hydrophilic compounds. The results obtained in this study can be applied to optimize the adsorption capacities of micropollutants using activated carbon in water treatment process. Copyright © 2014 Elsevier B.V. All rights reserved.

INTEGRATIVE SAMPLING OF ANTIBIOTICS AND OTHER PHARMACEUTICALLY-RELATED COMPOUNDS

EPA Science Inventory

Pharmaceuticals from human and veterinary use continually enter the environment through municipal wastewater treatment plants (WWTPs), surface runoff from animal waste, and direct disposal of unused medications. The presence of these chemicals, albeit often at subtherapeutic trac...

Does Compound I Vary Significantly between Isoforms of Cytochrome P450?

PubMed Central

2011-01-01

The cytochrome P450 (CYP) enzymes are important in many areas, including pharmaceutical development. Subtle changes in the electronic structure of the active species, Compound I, have been postulated previously to account partly for the experimentally observed differences in reactivity between isoforms. Current predictive models of CYP metabolism typically assume an identical Compound I in all isoforms. Here we present a method to calculate the electronic structure and to estimate the Fe–O bond enthalpy of Compound I, and apply it to several human and bacterial CYP isoforms. Conformational flexibility is accounted for by sampling large numbers of structures from molecular dynamics simulations, which are subsequently optimized with density functional theory (B3LYP) based quantum mechanics/molecular mechanics. The observed differences in Compound I between human isoforms are small: They are generally smaller than the spread of values obtained for the same isoform starting from different initial structures. Hence, it is unlikely that the variation in activity between human isoforms is due to differences in the electronic structure of Compound I. A larger difference in electronic structure is observed between the human isoforms and P450cam and may be explained by the slightly different hydrogen-bonding environment surrounding the cysteinyl sulfur. The presence of substrate in the active site of all isoforms studied appears to cause a slight decrease in the Fe–O bond enthalpy, apparently due to displacement of water out of the active site, suggesting that Compound I is less stable in the presence of substrate. PMID:21863858

Anti-cancer agents based on 4-(hetero)Ary1-1,2,5-oxadiazol-3-yl Amino derivatives and a method of making

DOEpatents

Gakh, Andrei A.; Krasavin, Mikhail; Karapetian, Ruben; Rufanov, Konstantin A.; Konstantinov, Igor; Godovykh, Elena; Soldatkina, Olga; Sosnov, Andrey V.

2013-01-29

The present disclosure relates to novel compounds that can be used as anti-cancer agents in the prostate cancer therapy. ##STR00001## In particular, the invention relates N-substituted derivatives of 4-(hetero)aryl-1,2,5-oxadiazol-3-yl amines having the structural Formula (I) and (II), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof. Meaning of R1 and R2 in the Formula (I) and (II) are defined in claim 1. The invention also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

RFID in the pharmaceutical industry: addressing counterfeits with technology.

PubMed

Taylor, Douglas

2014-11-01

The use of Radio Frequency Identification (RFID) in the pharmaceutical industry has grown in recent years. The technology has matured from its specialized tracking and retail uses to a systemic part of supply chain management in international pharmaceutical production and distribution. Counterfeit drugs, however, remain a significant challenge for governments, pharmaceutical companies, clinicians, and patients and the use of RFID to track these compounds represents an opportunity for development. This paper discusses the medical, technological, and economic factors that support widespread adoption of RFID technology in the pharmaceutical industry in an effort to prevent counterfeit medicines from harming patients and brand equity.

The Mulberry (Morus alba L.) Fruit-A Review of Characteristic Components and Health Benefits.

PubMed

Yuan, Qingxia; Zhao, Longyan

2017-12-06

Mulberry (Morus alba L.) fruit has a high yield in one fruiting season in many countries, especially in Asia, and a long history of use as an edible fruit and traditional medicine. A great diversity of nutritive compounds such as fatty acids, amino acids, vitamins, minerals, and bioactive compounds, including anthocyanins, rutin, quercetin, chlorogenic acid, and polysaccharides have been found in mulberry fruit depending on the cultivars and maturity stages. Furthermore, the extracts and active components of mulberry fruit have demonstrated numerous biological activities, including antioxidant, neuroprotective, antiatherosclerosis, immunomodulative, antitumor, antihyperglycemic, and hypolipidemic activities in in vitro and in vivo studies, and they have received increasing interest from researchers and pharmaceutical companies. Although some mechanistic studies further substantiate these potential health benefits of mulberry fruit, a need exists to make a better understanding of the roles of these compounds in traditional medicine and the diet. This review provides recent findings regarding the chemical constituents and biological activities of mulberry fruit, which may be useful for stimulating deep research of mulberry fruit and for predicting their uses as important and safe contributors to benefit human health.

Patents on Phytochemicals: Methodologies of Extraction, Application in Food and Pharmaceutical Industry.

PubMed

Ordaz-Trinidad, Nancy; Dorantes-Alvarez, Lidia; Salas-Benito, Juan

2015-01-01

Patents on phytochemicals are being registered worldwide. Such phytochemicals provide benefits to human health, and include terpenoids, phenolic compounds, alkaloids, lignin, and fiber. This review has the purpose to provide a comprehensive overview of patents published in the last five years about extraction of phytochemicals and their application in the food and pharmaceutical industry. Forty eight pa- tents were analyzed and classified in four topics of interest; 1) Extraction, 2) Functional foods, 3) Biological activity, and 4) Prevention of diseases. Extraction yield of phytochemicals is the critical step. The techniques to extract phytochemicals include enzymat- ic hydrolysis, nano-particulate precipitation, salts formation and combination of solvents; however, the use of ultrasound and microwave is increasing. Patents concerning functional foods include pediatric formulations, sport drink, and compo- sitions that produce beneficial effects. Biological activity of plant extracts tested in animals or cell cultures, as antioxidant, anti-inflammatory, anticancer activity, reduction of obesity and diabetes are presented in this review. Application of phy- tochemicals in the prevention and treatment of health disorders, such as diabetes, gastritis, enteritis, topical inflammation, macular degeneration, gingivitis, prostatic hyperplasia, urinary impairments. Patents revised include 30% methodologies for extraction of phytochemicals, 16% application of phytochem- icals in food matrixes to obtain functional foods, 18% biological activity of extracts or compounds and 36% application in the prevention and treatment of illness, which reveals a great interest to protect intellectual property concerning applica- tion of phytochemicals formulations for human health.

Design of experiments for microencapsulation applications: A review.

PubMed

Paulo, Filipa; Santos, Lúcia

2017-08-01

Microencapsulation techniques have been intensively explored by many research sectors such as pharmaceutical and food industries. Microencapsulation allows to protect the active ingredient from the external environment, mask undesired flavours, a possible controlled release of compounds among others. The purpose of this review is to provide a background of design of experiments in microencapsulation research context. Optimization processes are required for an accurate research in these fields and therefore, the right implementation of micro-sized techniques at industrial scale. This article critically reviews the use of the response surface methodologies in pharmaceutical and food microencapsulation research areas. A survey of optimization procedures in the literature, in the last few years is also presented. Copyright © 2017 Elsevier B.V. All rights reserved.

An industry update: the latest developments in Therapeutic delivery.

PubMed

Steinbach, Oliver C

2018-05-01

The present industry update covers the period of 1 January-31 January 2018, with information sourced from company press releases, regulatory and patent agencies as well as scientific literature. Several public offerings (Gecko, Insmed), licensing (Foresee) and commercialization agreements (Alnylam, Collegium Pharmaceutical) as well as patent filings (Elute) continue to prove the sustained investments in the drug delivery market. In increasing numbers, more effective ways to deliver the active ingredient to the right location and the right dose through devices (Boehringer Ingelheim's Respimat, Medtronics' SynchroMedII) or improved compound properties through formulation (Aquestive Therapeutics' PharmFilm, Noven Pharmaceuticals' transdermal patch) are reaching the market. Furthering biologics and gene delivery (Avacta, Bracco) proves that novel drug delivery technologies are successfully addressing more challenging drug formats.

Occurrence of Organic Wastewater Compounds in the Tinkers Creek Watershed and Two Other Tributaries to the Cuyahoga River, Northeast Ohio

USGS Publications Warehouse

Tertuliani, J.S.; Alvarez, D.A.; Furlong, E.T.; Meyer, M.T.; Zaugg, S.D.; Koltun, G.F.

2008-01-01

The U.S. Geological Survey - in cooperation with the Ohio Water Development Authority; National Park Service; Cities of Aurora, Bedford, Bedford Heights, Solon, and Twinsburg; and Portage and Summit Counties - and in collaboration with the Ohio Environmental Protection Agency, did a study to determine the occurrence and distribution of organic wastewater compounds (OWCs) in the Tinkers Creek watershed in northeastern Ohio. In the context of this report, OWCs refer to a wide range of compounds such as antibiotics, prescription and nonprescription pharmaceuticals, personal-care products, household and industrial compounds (for example, antimicrobials, fragrances, surfactants, fire retardants, and so forth) and a variety of other chemicals. Canisters containing polar organic integrative sampler (POCIS) and semipermeable membrane device (SPMD) media were deployed instream for a 28-day period in Mayand June 2006 at locations upstream and downstream from seven wastewater-treatment-plant (WWTP) outfalls in the Tinkers Creek watershed, at a site on Tinkers Creek downstream from all WWTP discharges, and at one reference site each in two nearby watersheds (Yellow Creek and Furnace Run) that drain to the Cuyahoga River. Streambed-sediment samples also were collected at each site when the canisters were retrieved. POCIS and SPMDs are referred to as 'passive samplers' because they sample compounds that they are exposed to without use of mechanical or moving parts. OWCs detected in POCIS and SPMD extracts are referred to in this report as 'detections in water' because both POCIS and SPMDs provided time-weighted measures of concentration in the stream over the exposure period. Streambed sediments also reflect exposure to OWCs in the stream over a long period of time and provide another OWC exposure pathway for aquatic organisms. Four separate laboratory methods were used to analyze for 32 antibiotic, 20 pharmaceutical, 57 to 66 wastewater, and 33 hydrophobic compounds. POCIS and streambed-sediment extracts were analyzed by both the pharmaceutical and wastewater methods. POCIS extracts also were analyzed by the antibiotic method, and SPMD extracts were analyzed by the hydrophobic-compound method. Analytes associated with a given laboratory method are referred to in aggregate by the method name (for example, antibiotic-method analytes are referred to as 'antibiotic compounds') even though some analytes associated with the method may not be strictly classified as such. In addition, some compounds were included in the analyte list for more than one laboratory method. For a given sample matrix, individual compounds detected by more than one analytical method are included independently in counts for each method. A total of 12 antibiotic, 20 pharmaceutical, 41 wastewater, and 22 hydrophobic compounds were detected in water at one or more sites. Eight pharmaceutical and 37 wastewater compounds were detected in streambed sediments. The numbers of detections at reference sites tended to be in the low range of detection counts observed in the Tinkers Creek watershed for a given analytical method. Also, the total numbers of compounds detected in water and sediment at the reference sites were less than the total numbers of compounds detected at sites in the Tinkers Creek watershed. With the exception of hydrophobic compounds, it was common at most sites to have more compounds detected in samples collected downstream from WWTP outfalls than in corresponding samples collected upstream from the outfalls. This was particularly true for antibiotic, pharmaceutical, and wastewater compounds in water. In contrast, it was common to have more hydrophobic compounds detected in samples collected upstream from WWTP outfalls than downstream. Caffeine, fluoranthene, N,N-diethyl-meta-toluamide (DEET), phenanthrene, and pyrene were detected in water at all sites in the Tinkers Creek watershed, irrespective of whether the site was upstream or downs

Use of sub-micron sized resin particles for removal of endocrine disrupting compounds and pharmaceuticals from water and wastewater.

PubMed

Murray, Audrey; Örmeci, Banu; Lai, Edward P C

2017-01-01

Endocrine disrupting compounds (EDCs) and pharmaceuticals pose a challenge for water and wastewater treatment because they exist at very low concentrations in the presence of substances at much higher concentrations competing for adsorption sites. Sub-micron sized resin particles (approximately 300nm in diameter) (SMR) were tested to evaluate their potential as a treatment for EDCs including: 17-β estradiol (E2), 17-α ethinylestradiol (EE2), estrone (E1), bisphenol A (BPA), and diethylstilbestrol (DES) as well as 12 pharmaceuticals. SMR were able to remove 98% of spiked E2, 80% of EE2, 87% of BPA, and up to 97% of DES from water. For a 0.5ppm mixture of E2, EE2, E1, BPA and DES, the minimum removal was 24% (E2) and the maximum was 49% (DES). They were also able to remove the pharmaceuticals from deionized water and wastewater. Overall, SMR are a promising advanced treatment for removal of both EDCs and pharmaceuticals. Copyright © 2016. Published by Elsevier B.V.

Antimicrobial active herbal compounds against Acinetobacter baumannii and other pathogens.

PubMed

Tiwari, Vishvanath; Roy, Ranita; Tiwari, Monalisa

2015-01-01

Bacterial pathogens cause a number of lethal diseases. Opportunistic bacterial pathogens grouped into ESKAPE pathogens that are linked to the high degree of morbidity, mortality and increased costs as described by Infectious Disease Society of America. Acinetobacter baumannii is one of the ESKAPE pathogens which cause respiratory infection, pneumonia and urinary tract infections. The prevalence of this pathogen increases gradually in the clinical setup where it can grow on artificial surfaces, utilize ethanol as a carbon source and resists desiccation. Carbapenems, a β-lactam, are the most commonly prescribed drugs against A. baumannii. The high level of acquired and intrinsic carbapenem resistance mechanisms acquired by these bacteria makes their eradication difficult. The pharmaceutical industry has no solution to this problem. Hence, it is an urgent requirement to find a suitable alternative to carbapenem, a commonly prescribed drug for Acinetobacter infection. In order to do this, here we have made an effort to review the active compounds of plants that have potent antibacterial activity against many bacteria including carbapenem resistant strain of A. baumannii. We have also briefly highlighted the separation and identification methods used for these active compounds. This review will help researchers involved in the screening of herbal active compounds that might act as a replacement for carbapenem.

Pesticide monitoring in surface water and groundwater using passive samplers

NASA Astrophysics Data System (ADS)

Kodes, V.; Grabic, R.

2009-04-01

Passive samplers as screening devices have been used within a czech national water quality monitoring network since 2002 (SPMD and DGT samplers for non polar substances and metals). The passive sampler monitoring of surface water was extended to polar substances, in 2005. Pesticide and pharmaceutical POCIS samplers have been exposed in surface water at 21 locations and analysed for polar pesticides, perfluorinated compounds, personal care products and pharmaceuticals. Pesticide POCIS samplers in groundwater were exposed at 5 locations and analysed for polar pesticides. The following active substances of plant protection products were analyzed in surface water and groundwater using LC/MS/MS: 2,4,5-T, 2,4-D, Acetochlor, Alachlor, Atrazine, Atrazine_desethyl, Azoxystrobin, Bentazone, Bromacil, Bromoxynil, Carbofuran, Clopyralid, Cyanazin, Desmetryn, Diazinon, Dicamba, Dichlobenil, Dichlorprop, Dimethoat, Diuron, Ethofumesate, Fenarimol, Fenhexamid, Fipronil, Fluazifop-p-butyl, Hexazinone, Chlorbromuron, Chlorotoluron, Imazethapyr, Isoproturon, Kresoxim-methyl, Linuron, MCPA, MCPP, Metalaxyl, Metamitron, Methabenzthiazuron, Methamidophos, Methidathion, Metobromuron, Metolachlor, Metoxuron, Metribuzin, Monolinuron, Nicosulfuron, Phorate, Phosalone, Phosphamidon, Prometryn, Propiconazole, Propyzamide, Pyridate, Rimsulfuron, Simazine, Tebuconazole, Terbuthylazine, Terbutryn, Thifensulfuron-methyl, Thiophanate-methyl and Tri-allate. The POCIS samplers performed very well being able to provide better picture than grab samples. The results show that polar pesticides and also perfluorinated compounds, personal care products and pharmaceuticals as well occur in hydrosphere of the Czech republic. Acknowledgment: Authors acknowledge the financial support of grant No. 2B06095 by the Ministry of Education, Youth and Sports.

Porphyrins for boron neutron capture therapy

DOEpatents

Miura, Michiko; Gabel, Detlef

1990-01-01

Novel compounds for treatment of brain tumors in Boron Neutron Capture Therapy are disclosed. A method for preparing the compounds as well as pharmaceutical compositions containing said compounds are also disclosed. The compounds are water soluble, non-toxic and non-labile boronated porphyrins which show significant uptake and retention in tumors.

Impact of sludge stabilization processes and sludge origin (urban or hospital) on the mobility of pharmaceutical compounds following sludge landspreading in laboratory soil-column experiments.

PubMed

Lachassagne, Delphine; Soubrand, Marilyne; Casellas, Magali; Gonzalez-Ospina, Adriana; Dagot, Christophe

2015-11-01

This study aimed to determine the effect of sludge stabilization treatments (liming and anaerobic digestion) on the mobility of different pharmaceutical compounds in soil amended by landspreading of treated sludge from different sources (urban and hospital). The sorption and desorption potential of the following pharmaceutical compounds: carbamazepine (CBZ), ciprofloxacin (CIP), sulfamethoxazole (SMX), salicylic acid (SAL), ibuprofen (IBU), paracetamol (PAR), diclofenac (DIC), ketoprofen (KTP), econazole (ECZ), atenolol (ATN), and their solid-liquid distribution during sludge treatment (from thickening to stabilization) were investigated in the course of batch testing. The different sludge samples were then landspread at laboratory scale and leached with an artificial rain simulating 1 year of precipitation adapted to the surface area of the soil column used. The quality of the resulting leachate was investigated. Results showed that ibuprofen had the highest desorption potential for limed and digested urban and hospital sludge. Ibuprofen, salicylic acid, diclofenac, and paracetamol were the only compounds found in amended soil leachates. Moreover, the leaching potential of these compounds and therefore the risk of groundwater contamination depend mainly on the origin of the sludge because ibuprofen and diclofenac were present in the leachates of soils amended with urban sludge, whereas paracetamol and salicylic acid were found only in the leachates of soils amended with hospital sludge. Although carbamazepine, ciprofloxacin, sulfamethoxazole, ketoprofen, econazole, and atenolol were detected in some sludge, they were not present in any leachate. This reflects either an accumulation and/or (bio)degradation of these compounds (CBZ, CIP, SMX, KTP, ECZ, and ATN ), thus resulting in very low mobility in soil. Ecotoxicological risk assessment, evaluated by calculating the risk quotients for each studied pharmaceutical compound, revealed no high risk due to the application on the soil of sludge stabilized by liming or anaerobic digestion.

An Empirical Analysis of Primary and Secondary Pharmaceutical Patents in Chile

PubMed Central

Abud, María José; Hall, Bronwyn; Helmers, Christian

2015-01-01

We analyze the patent filing strategies of foreign pharmaceutical companies in Chile distinguishing between “primary” (active ingredient) and “secondary” patents (patents on modified compounds, formulations, dosages, particular medical uses, etc.). There is prior evidence that secondary patents are used by pharmaceutical originator companies in the U.S. and Europe to extend patent protection on drugs in length and breadth. Using a novel dataset that comprises all drugs registered in Chile between 1991 and 2010 as well as the corresponding patents and trademarks, we find evidence that foreign originator companies pursue similar strategies in Chile. We find a primary to secondary patents ratio of 1:4 at the drug-level, which is comparable to the available evidence for Europe; most secondary patents are filed over several years following the original primary patent and after the protected active ingredient has obtained market approval in Chile. This points toward effective patent term extensions through secondary patents. Secondary patents dominate “older” therapeutic classes like anti-ulcer and anti-depressants. In contrast, newer areas like anti-virals and anti-neoplastics (anti-cancer) have a much larger share of primary patents. PMID:25915050

Azole fungicides: occurrence and fate in wastewater and surface waters.

PubMed

Kahle, Maren; Buerge, Ignaz J; Hauser, Andrea; Müller, Markus D; Poiger, Thomas

2008-10-01

The mode of action of azole compounds implies a potential to affect endocrine systems of different organisms and is reason for environmental concern. The occurrence and fate of nine agricultural azole fungicides, some of them also used as biocides, and four azole pharmaceuticals were studied in wastewater treatment plants (WWTPs) and lakes in Switzerland. Two pharmaceuticals (fluconazole, clotrimazole, 10-110 ng L(-1)) and two biocides (propiconazole, tebuconazole, 1-30 ng L(-1)) were consistently observed in WWTP influents. Loads determined in untreated and treated wastewater indicated thatfluconazole, propiconazole, and tebuconazole were largely unaffected by wastewater treatment, but clotrimazole was effectively eliminated (> 80%). Incubation studies with activated sludge showed no degradation for fluconazole and clotrimazole within 24 h, but strong sorption of clotrimazole to activated sludge. Slow degradation and some sorption were observed for tebuconazole and propiconazole (degradation half-lives, 2-3 d). In lakes, fluconazole, propiconazole, and tebuconazole were detected at low nanogram-per-liter levels. Concentrations of the pharmaceutical fluconazole correlated with the expected contamination by domestic wastewater, but not those of the biocides. Per capita loads of propiconazole and tebuconazole in lakes suggested additional inputs; for example, from agricultural use or urban runoff rainwater.

Prospects of pharmaceuticals and biopharmaceuticals loaded microparticles prepared by double emulsion technique for controlled delivery

PubMed Central

Giri, Tapan Kumar; Choudhary, Chhatrapal; Ajazuddin; Alexander, Amit; Badwaik, Hemant; Tripathi, Dulal Krishna

2012-01-01

Several methods and techniques are potentially useful for the preparation of microparticles in the field of controlled drug delivery. The type and the size of the microparticles, the entrapment, release characteristics and stability of drug in microparticles in the formulations are dependent on the method used. One of the most common methods of preparing microparticles is the single emulsion technique. Poorly soluble, lipophilic drugs are successfully retained within the microparticles prepared by this method. However, the encapsulation of highly water soluble compounds including protein and peptides presents formidable challenges to the researchers. The successful encapsulation of such compounds requires high drug loading in the microparticles, prevention of protein and peptide degradation by the encapsulation method involved and predictable release, both rate and extent, of the drug compound from the microparticles. The above mentioned problems can be overcome by using the double emulsion technique, alternatively called as multiple emulsion technique. Aiming to achieve this various techniques have been examined to prepare stable formulations utilizing w/o/w, s/o/w, w/o/o, and s/o/o type double emulsion methods. This article reviews the current state of the art in double emulsion based technologies for the preparation of microparticles including the investigation of various classes of substances that are pharmaceutically and biopharmaceutically active. PMID:23960828

From municipal sewage to drinking water: fate and removal of pharmaceutical residues in the aquatic environment in urban areas.

PubMed

Heberer, Th; Reddersen, K; Mechlinski, A

2002-01-01

Recently, the occurrence and fate of pharmaceutically active compounds (PhACs) in the aquatic environment was recognized as one of the emerging issues in environmental chemistry and as a matter of public concern. Residues of PhACs have been found as contaminants in sewage, surface, and ground- and drinking water samples. Since June 2000, a new long-term monitoring program of sewage, surface, ground- and drinking water has been carried out in Berlin, Germany. Samples, collected periodically from selected sites in the Berlin area, are investigated for residues of PhACs and related contaminants. The purpose of this monitoring is to investigate these compounds over a long time period to get more reliable data on their occurrence and fate in the different aquatic compartments. Moreover, the surface water investigations allow the calculation of season-dependent contaminant loads in the Berlin waters. In the course of the monitoring program, PhACs and some other polar compounds were detected at concentrations up to the microg/L-level in all compartments of the Berlin water cycle. The monitoring is accompanied and supported by several other investigations such as laboratory column experiments and studies on bank filtration and drinking water treatment using conventional or membrane filtration techniques.

Adsorption of pharmaceuticals onto activated carbon fiber cloths - Modeling and extrapolation of adsorption isotherms at very low concentrations.

PubMed

Fallou, Hélène; Cimetière, Nicolas; Giraudet, Sylvain; Wolbert, Dominique; Le Cloirec, Pierre

2016-01-15

Activated carbon fiber cloths (ACFC) have shown promising results when applied to water treatment, especially for removing organic micropollutants such as pharmaceutical compounds. Nevertheless, further investigations are required, especially considering trace concentrations, which are found in current water treatment. Until now, most studies have been carried out at relatively high concentrations (mg L(-1)), since the experimental and analytical methodologies are more difficult and more expensive when dealing with lower concentrations (ng L(-1)). Therefore, the objective of this study was to validate an extrapolation procedure from high to low concentrations, for four compounds (Carbamazepine, Diclofenac, Caffeine and Acetaminophen). For this purpose, the reliability of the usual adsorption isotherm models, when extrapolated from high (mg L(-1)) to low concentrations (ng L(-1)), was assessed as well as the influence of numerous error functions. Some isotherm models (Freundlich, Toth) and error functions (RSS, ARE) show weaknesses to be used as an adsorption isotherms at low concentrations. However, from these results, the pairing of the Langmuir-Freundlich isotherm model with Marquardt's percent standard of deviation was evidenced as the best combination model, enabling the extrapolation of adsorption capacities by orders of magnitude. Copyright © 2015 Elsevier Ltd. All rights reserved.

Orlistat interaction with sibutramine and carnitine. A physicochemical and theoretical study

NASA Astrophysics Data System (ADS)

Nicolás-Vázquez, Inés; Hinojosa Torres, Jaime; Cruz Borbolla, Julián; Miranda Ruvalcaba, René; Aceves-Hernández, Juan Manuel

2014-03-01

Chemical degradation of orlistat, (ORT) after melting and reaction of decomposition byproducts with sibutramine, SIB was studied. Interactions between the active pharmaceutical ingredients by using thermal analysis, TA, methods and other experimental techniques such as PXRD, IR and UV-vis spectroscopies were carried out to investigate chemical reactions between components. It was found that orlistat melts with decomposition and byproducts quickly affect sibutramine molecule and then reacting also with carnitine, CRN when the three active pharmaceutical ingredients (API's) are mixed. However ORT byproducts do not react when ORT is mixed only with carnitine. It was found that compounds containing chlorine atoms react easily with orlistat when the temperature increases up to its melting point. Some reaction mechanisms of orlistat decomposition are proposed, the fragments in the mechanisms were found in the corresponding mass spectra. Results obtained indicate that special studies should be carried out in the formulation stage before the final composition of a poly-pill could be established. Similar results are commonly found for compounds very prone to react in presence of water, light and/or temperature. In order to explain the reactivity of orlistat with sibutramine and carnitine, theoretical calculations were carried out and the results are in agreement with the experimental results.

Dammarane triterpenoids for pharmaceutical use: a patent review (2005 - 2014).

PubMed

Cao, Jiaqing; Zhang, Xiaoshu; Qu, Fanzhi; Guo, Zhenghong; Zhao, Yuqing

2015-07-01

Dammarane triterpenoids, the main secondary metabolites of Panax ginseng, are very important natural compounds with remarkable biological activity. They could be isolated from the plants of Panax or other genus, as well as through the modifications of certain natural products. This review is a collection of a number of patents (2005 - 2014) that describe the dammarane triterpenoids for therapeutic or preventive uses on numerous common diseases. In this review, patents from 2005 to 2014 on chemical structures and treatment of different diseases by dammarane triterpenoids have been summarized. The SciFinder and the World Intellectual Property Organisation databases have been used as main sources for the search. In the last decade, over 90 patents concerning dammarane derivatives for pharmaceutical have been published. These types of compounds could be used as agents for prevention and treatment of various kinds of diseases, such as cancer, diabetes mellitus and metabolic syndrome, hyperlipidemia, cardiovascular and cerebrovascular disease, aging, neurodegenerative disease, bone disease, liver disease, kidney disease, gastrointestinal disease, depression-type mental illness and skin aging. Rare plants, except for Panax genus, which contain dammarane triterpenoids should be studied extensively. In addition, more dammarane triterpenoids with good biological activity, especially the aglycones possessing novel side chain, should be prepared using chemical modification. Finally, pharmacological effects of dammarane triterpenoids should be further studied.

Uncovering the repertoire of fungal secondary metabolites: From Fleming's laboratory to the International Space Station.

PubMed

Boruta, Tomasz

2018-01-01

Fungi produce a variety of secondary metabolites (SMs), low-molecular weight compounds associated with many potentially useful biologic activities. The examples of biotechnologically relevant fungal metabolites include penicillin, a β-lactam antibiotic, and lovastatin, a cholesterol-lowering drug. The discovery of pharmaceutical lead compounds within the microbial metabolic pools relies on the selection and biochemical characterization of promising strains. Not all SMs are produced under standard cultivation conditions, hence the uncovering of chemical potential of investigated strains often requires the use of induction strategies to awake the associated biosynthetic genes. Triggering the secondary metabolic pathways can be achieved through the variation of cultivation conditions and growth media composition. The alternative strategy is to use genetic engineering to activate the respective genomic segments, e.g. by the manipulation of regulators or chromatin-modifying enzymes. Recently, whole-genome sequencing of several fungi isolated from the Chernobyl accident area was reported by Singh et al. (Genome Announc 2017; 5:e01602-16). These strains were selected for exposure to microgravity at the International Space Station. Biochemical characterization of fungi cultivated under extreme conditions is likely to provide valuable insights into the adaptation mechanism associated with metabolism and, possibly, a catalog of novel molecules of potential pharmaceutical importance.

Unraveling the potential of a combined nitritation-anammox biomass towards the biodegradation of pharmaceutically active compounds.

PubMed

Kassotaki, Elissavet; Pijuan, Maite; Joss, Adriano; Borrego, Carles M; Rodriguez-Roda, Ignasi; Buttiglieri, Gianluigi

2018-05-15

In the past few years, anaerobic ammonium oxidation-based processes have attracted a lot of attention for their implementation at the mainstream line of wastewater treatment plants, due to the possibility of leading to energy autarky if combined with anaerobic digestion. However, little is known about the potential degradation of micropollutants by the microbial groups responsible of these processes and the few results available are inconclusive. This study aimed to assess the degradation capability of biomass withdrawn from a combined nitritation/anaerobic ammonium oxidation (combined N/A) pilot plant towards five pharmaceutically active compounds (ibuprofen, sulfamethoxazole, metoprolol, venlafaxine and carbamazepine). Batch experiments were performed under different conditions by selectively activating or inhibiting different microbial groups: i) regular combined N/A operation, ii) aerobic (optimal for nitrifying bacteria), iii) aerobic with allylthiourea (an inhibitor of ammonia monooxygenase, enzyme of ammonia oxidizing bacteria), iv) anoxic (optimal for anaerobic ammonium oxidizing bacteria), v) aerobic with acetate (optimal for heterotrophic bacteria) and vi) anoxic with acetate (optimal for heterotrophic denitrifying bacteria). Ibuprofen was the most biodegradable compound being significantly degraded (49-100%) under any condition except heterotrophic denitrification. Sulfamethoxazole, exhibited the highest removal (70%) under optimal conditions for nitrifying bacteria but in the rest of the experiments anoxic conditions were found to be slightly more favorable (up to 58%). For metoprolol the highest performance was obtained under anoxic conditions favoring anammox bacteria (62%). Finally, carbamazepine and venlafaxine were hardly removed (≤10% in the majority of cases). Taken together, these results suggest the specificity of different microbial groups that in combination with alternating operational parameters can lead to enhanced removal of some micropollutants. Copyright © 2017 Elsevier B.V. All rights reserved.

Antioxidant Activity of Hawaiian Marine Algae

PubMed Central

Kelman, Dovi; Posner, Ellen Kromkowski; McDermid, Karla J.; Tabandera, Nicole K.; Wright, Patrick R.; Wright, Anthony D.

2012-01-01

Marine algae are known to contain a wide variety of bioactive compounds, many of which have commercial applications in pharmaceutical, medical, cosmetic, nutraceutical, food and agricultural industries. Natural antioxidants, found in many algae, are important bioactive compounds that play an important role against various diseases and ageing processes through protection of cells from oxidative damage. In this respect, relatively little is known about the bioactivity of Hawaiian algae that could be a potential natural source of such antioxidants. The total antioxidant activity of organic extracts of 37 algal samples, comprising of 30 species of Hawaiian algae from 27 different genera was determined. The activity was determined by employing the FRAP (Ferric Reducing Antioxidant Power) assays. Of the algae tested, the extract of Turbinaria ornata was found to be the most active. Bioassay-guided fractionation of this extract led to the isolation of a variety of different carotenoids as the active principles. The major bioactive antioxidant compound was identified as the carotenoid fucoxanthin. These results show, for the first time, that numerous Hawaiian algae exhibit significant antioxidant activity, a property that could lead to their application in one of many useful healthcare or related products as well as in chemoprevention of a variety of diseases including cancer. PMID:22412808

Compound Libraries: Recent Advances and Their Applications in Drug Discovery.

PubMed

Gong, Zhen; Hu, Guoping; Li, Qiang; Liu, Zhiguo; Wang, Fei; Zhang, Xuejin; Xiong, Jian; Li, Peng; Xu, Yan; Ma, Rujian; Chen, Shuhui; Li, Jian

2017-01-01

Hit identification is the starting point of small-molecule drug discovery and is therefore very important to the pharmaceutical industry. One of the most important approaches to identify a new hit is to screen a compound library using an in vitro assay. High-throughput screening has made great contributions to drug discovery since the 1990s but requires expensive equipment and facilities, and its success depends on the size of the compound library. Recent progress in the development of compound libraries has provided more efficient ways to identify new hits for novel drug targets, thereby helping to promote the development of the pharmaceutical industry, especially for firstin- class drugs. A multistage and systematic research of articles published between 1986 and 2017 has been performed, which was organized into 5 sections and discussed in detail. In this review, the sources and classification of compound libraries are summarized. The progress made in combinatorial libraries and DNA-encoded libraries is reviewed. Library design methods, especially for focused libraries, are introduced in detail. In the final part, the status of the compound libraries at WuXi is reported. The progress related to compound libraries, especially drug template libraries, DELs, and focused libraries, will help to identify better hits for novel drug targets and promote the development of the pharmaceutical industry. Moreover, these libraries can facilitate hit identification, which benefits most research organizations, including academics and small companies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ranking of concern, based on environmental indexes, for pharmaceutical and personal care products: an application to the Spanish case.

PubMed

Ortiz de García, Sheyla; Pinto, Gilberto Pinto; García-Encina, Pedro A; Irusta Mata, Rubén I

2013-11-15

A wide range of Pharmaceuticals and Personal Care Products (PPCPs) are present in the environment, and many of their adverse effects are unknown. The emergence of new compounds or changes in regulations have led to dynamical studies of occurrence, impact and treatment, which consider geographical areas and trends in consumption and innovation in the pharmaceutical industry. A Quantitative study of Structure-Activity Relationship ((Q)SAR) was performed to assess the possible adverse effects of ninety six PPCPs and metabolites with negligible experimental data and establish a ranking of concern, which was supported by the EPA EPI Suite™ interface. The environmental and toxicological indexes, the persistence (P), the bioaccumulation (B), the toxicity (T) (extensive) and the occurrence in Spanish aquatic environments (O) (intensive) were evaluated. The most hazardous characteristics in the largest number of compounds were generated by the P index, followed by the T and B indexes. A high number of metabolites has a concern score equal to or greater than their parent compounds. Three PBT and OPBT rankings of concern were proposed using the total and partial ranking method (supported by a Hasse diagram) by the Decision Analysis by Ranking Techniques (DART) tool, which was recently recommended by the European Commission. An analysis of the sensibility of the relative weights of these indexes has been conducted. Hormones, antidepressants (and their metabolites), blood lipid regulators and all of the personal care products considered in this study were at the highest levels of risk according to the PBT and OPBT total rankings. Furthermore, when the OPBT partial ranking was performed, X-ray contrast media, H2 blockers and some antibiotics were included at the highest level of concern. It is important to improve and incorporate useful indexes for the predicted environmental impact of PPCPs and metabolites and thus focus experimental analysis on the compounds that require urgent attention. Copyright © 2013 Elsevier Ltd. All rights reserved.

Analytical tools employed to determine pharmaceutical compounds in wastewaters after application of advanced oxidation processes.

PubMed

Afonso-Olivares, Cristina; Montesdeoca-Esponda, Sarah; Sosa-Ferrera, Zoraida; Santana-Rodríguez, José Juan

2016-12-01

Today, the presence of contaminants in the environment is a topic of interest for society in general and for the scientific community in particular. A very large amount of different chemical substances reaches the environment after passing through wastewater treatment plants without being eliminated. This is due to the inefficiency of conventional removal processes and the lack of government regulations. The list of compounds entering treatment plants is gradually becoming longer and more varied because most of these compounds come from pharmaceuticals, hormones or personal care products, which are increasingly used by modern society. As a result of this increase in compound variety, to address these emerging pollutants, the development of new and more efficient removal technologies is needed. Different advanced oxidation processes (AOPs), especially photochemical AOPs, have been proposed as supplements to traditional treatments for the elimination of pollutants, showing significant advantages over the use of conventional methods alone. This work aims to review the analytical methodologies employed for the analysis of pharmaceutical compounds from wastewater in studies in which advanced oxidation processes are applied. Due to the low concentrations of these substances in wastewater, mass spectrometry detectors are usually chosen to meet the low detection limits and identification power required. Specifically, time-of-flight detectors are required to analyse the by-products.

Irradiation treatment of pharmaceutical and personal care products (PPCPs) in water and wastewater: An overview

NASA Astrophysics Data System (ADS)

Wang, Jianlong; Chu, Libing

2016-08-01

Pharmaceutical and personal care products (PPCPs), especially the pharmaceutically active compounds (PhACs) such as antibiotics and hormones have attracted great concerns worldwide for their persistence and potential threat to ecosystem and public health. This paper presents an overview on the ionizing irradiation-induced degradation of PPCPs in aqueous solution. Parameters that affect PPCPs degradation, such as the absorbed dose, solution pH, dose rate, water matrices and the presence of some inorganic ions and humic acid are evaluated. The mechanism and pathways of radiolytic degradation of PPCPs are reviewed. In many cases, PPCPs such as antibiotics and X-ray contrast agent could be removed completely by radiation, but a higher absorbed dose was needed for their mineralization and toxicity reduction. The combination of ionizing irradiation with other methods such as H2O2, ozonation and TiO2 nanoparticles could improve the degradation efficacy and reduce the cost. Ionizing irradiation is a promising alternative for degradation of PPCPs in aqueous solution.

Spatial and temporal occurrence of pharmaceuticals and illicit drugs in the aqueous environment and during wastewater treatment: new developments.

PubMed

Baker, David R; Kasprzyk-Hordern, Barbara

2013-06-01

This paper presents, for the first time, spatial and temporal occurrence of a comprehensive set of >60 pharmaceuticals, illicit drugs and their metabolites in wastewater (7 wastewater treatment plants utilising different treatment technologies) and a major river in the UK over a 12 month period. This paper also undertakes a comparison of the efficiency of processes utilised during wastewater treatment and it discusses under-researched aspects of pharmaceuticals and illicit drugs in the environment including sorption to solids and stereoselectivity in the fate of chiral drugs during wastewater treatment and in receiving waters. The removal efficiency of analytes strongly depended on the type of wastewater treatment technology employed and denoted <50% or >60% in the case of tricking filter and activated sludge respectively. It should be stressed, however, that the removal rate was highly variable for different groups of compounds. A clear increase in the cumulative concentration of all monitored compounds was observed in receiving waters; thus highlighting the impact of WWTP discharge on water quality and the importance of the removal efficiency of WWTPs. No seasonal variation was observed with regard to the total load of targeted compounds in the river each month. The concentration of each analyte was largely dependent on rainfall and the dilution factor of WWTP discharge. These results indicate that although the drugs of abuse are not present at very high concentrations in river water (typically low ng L(-1) levels), their occurrence and possible synergic action is of concern, and the study of multiple groups of drugs of abuse is of significant importance. Copyright © 2013 Elsevier B.V. All rights reserved.

Myricetin: A Dietary Molecule with Diverse Biological Activities

PubMed Central

Semwal, Deepak Kumar; Semwal, Ruchi Badoni; Combrinck, Sandra; Viljoen, Alvaro

2016-01-01

Myricetin is a common plant-derived flavonoid and is well recognised for its nutraceuticals value. It is one of the key ingredients of various foods and beverages. The compound exhibits a wide range of activities that include strong anti-oxidant, anticancer, antidiabetic and anti-inflammatory activities. It displays several activities that are related to the central nervous system and numerous studies have suggested that the compound may be beneficial to protect against diseases such as Parkinson’s and Alzheimer’s. The use of myricetin as a preserving agent to extend the shelf life of foods containing oils and fats is attributed to the compound’s ability to protect lipids against oxidation. A detailed search of existing literature revealed that there is currently no comprehensive review available on this important molecule. Hence, the present work includes the history, synthesis, pharmaceutical applications and toxicity studies of myricetin. This report also highlights structure-activity relationships and mechanisms of action for various biological activities. PMID:26891321

Combining cationic and anionic mixed-mode sorbents in a single cartridge to extract basic and acidic pharmaceuticals simultaneously from environmental waters.

PubMed

Salas, Daniela; Borrull, Francesc; Fontanals, Núria; Marcé, Rosa Maria

2018-01-01

The aim of the present study is to broaden the applications of mixed-mode ion-exchange solid-phase extraction sorbents to extract both basic and acidic compounds simultaneously by combining the sorbents in a single cartridge and developing a simplified extraction procedure. Four different cartridges containing negative and positive charges in the same configuration were evaluated and compared to extract a group of basic, neutral, and acidic pharmaceuticals selected as model compounds. After a thorough optimization of the extraction conditions, the four different cartridges showed to be capable of retaining basic and acidic pharmaceuticals simultaneously through ionic interactions, allowing the introduction of a washing step with 15 mL methanol to eliminate interferences retained by hydrophobic interactions. Using the best combined cartridge, a method was developed, validated, and further applied to environmental waters to demonstrate that the method is promising for the extraction of basic and acidic compounds from very complex samples.

Integrated (Meta) Genomic and Synthetic Biology Approaches to Develop New Biocatalysts

PubMed Central

Parages, María L.; Gutiérrez-Barranquero, José A.; Reen, F. Jerry; Dobson, Alan D.W.; O’Gara, Fergal

2016-01-01

In recent years, the marine environment has been the subject of increasing attention from biotechnological and pharmaceutical industries as a valuable and promising source of novel bioactive compounds. Marine biodiscovery programmes have begun to reveal the extent of novel compounds encoded within the enormous bacterial richness and diversity of the marine ecosystem. A combination of unique physicochemical properties and spatial niche-specific substrates, in wide-ranging and extreme habitats, underscores the potential of the marine environment to deliver on functionally novel biocatalytic activities. With the growing need for green alternatives to industrial processes, and the unique transformations which nature is capable of performing, marine biocatalysts have the potential to markedly improve current industrial pipelines. Furthermore, biocatalysts are known to possess chiral selectivity and specificity, a key focus of pharmaceutical drug design. In this review, we discuss how the explosion in genomics based sequence analysis, allied with parallel developments in synthetic and molecular biology, have the potential to fast-track the discovery and subsequent improvement of a new generation of marine biocatalysts. PMID:27007381

Photosynthetic Pigments in Diatoms

PubMed Central

Kuczynska, Paulina; Jemiola-Rzeminska, Malgorzata; Strzalka, Kazimierz

2015-01-01

Photosynthetic pigments are bioactive compounds of great importance for the food, cosmetic, and pharmaceutical industries. They are not only responsible for capturing solar energy to carry out photosynthesis, but also play a role in photoprotective processes and display antioxidant activity, all of which contribute to effective biomass and oxygen production. Diatoms are organisms of a distinct pigment composition, substantially different from that present in plants. Apart from light-harvesting pigments such as chlorophyll a, chlorophyll c, and fucoxanthin, there is a group of photoprotective carotenoids which includes β-carotene and the xanthophylls, diatoxanthin, diadinoxanthin, violaxanthin, antheraxanthin, and zeaxanthin, which are engaged in the xanthophyll cycle. Additionally, some intermediate products of biosynthetic pathways have been identified in diatoms as well as unusual pigments, e.g., marennine. Marine algae have become widely recognized as a source of unique bioactive compounds for potential industrial, pharmaceutical, and medical applications. In this review, we summarize current knowledge on diatom photosynthetic pigments complemented by some new insights regarding their physico-chemical properties, biological role, and biosynthetic pathways, as well as the regulation of pigment level in the cell, methods of purification, and significance in industries. PMID:26389924

Multi-class of endocrine disrupting compounds in aquaculture ecosystems and health impacts in exposed biota.

PubMed

Ismail, Nur Afifah Hanun; Wee, Sze Yee; Aris, Ahmad Zaharin

2017-12-01

Fishes are a major protein food source for humans, with a high economic value in the aquaculture industry. Because endocrine disrupting compounds (EDCs) have been introduced into aquatic ecosystems, the exposure of humans and animals that depend on aquatic foods, especially fishes, should be seriously considered. EDCs are emerging pollutants causing global concern because they can disrupt the endocrine system in aquatic organisms, mammals, and humans. These pollutants have been released into the environment through many sources, e.g., wastewater treatment plants, terrestrial run-off (industrial activities, pharmaceuticals, and household waste), and precipitation. The use of pharmaceuticals, pesticides, and fertilizers for maintaining and increasing fish health and growth also contributes to EDC pollution in the water body. Human and animal exposure to EDCs occurs via ingestion of contaminated matrices, especially aquatic foodstuffs. This paper aims to review human EDC exposure via fish consumption. In respect to the trace concentration of EDCs in fish, types of instrument and clean-up method are of great concerns. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using containerless methods to develop amorphous pharmaceuticals.

PubMed

Weber, J K R; Benmore, C J; Suthar, K J; Tamalonis, A J; Alderman, O L G; Sendelbach, S; Kondev, V; Yarger, J; Rey, C A; Byrn, S R

2017-01-01

Many pipeline drugs have low solubility in their crystalline state and require compounding in special dosage forms to increase bioavailability for oral administration. The use of amorphous formulations increases solubility and uptake of active pharmaceutical ingredients. These forms are rapidly gaining commercial importance for both pre-clinical and clinical use. Synthesis of amorphous drugs was performed using an acoustic levitation containerless processing method and spray drying. The structure of the products was investigated using in-situ high energy X-ray diffraction. Selected solvents for processing drugs were investigated using acoustic levitation. The stability of amorphous samples was measured using X-ray diffraction. Samples processed using both spray drying and containerless synthesis were compared. We review methods for making amorphous pharmaceuticals and present data on materials made by containerless processing and spray drying. It was shown that containerless processing using acoustic levitation can be used to make phase-pure forms of drugs that are known to be difficult to amorphize. The stability and structure of the materials was investigated in the context of developing and making clinically useful formulations. Amorphous compounds are emerging as an important component of drug development and for the oral delivery of drugs with low solubility. Containerless techniques can be used to efficiently synthesize small quantities of pure amorphous forms that are potentially useful in pre-clinical trials and for use in the optimization of clinical products. Developing new pharmaceutical products is an essential enterprise to improve patient outcomes. The development and application of amorphous pharmaceuticals to increase absorption is rapidly gaining importance and it provides opportunities for breakthrough research on new drugs. There is an urgent need to solve problems associated with making formulations that are both stable and that provide high bioavailability. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo. Copyright © 2016 Elsevier B.V. All rights reserved.

Bioaccumulation of pharmaceutically active compounds and endocrine disrupting chemicals in aquatic macrophytes: Results of hydroponic experiments with Echinodorus horemanii and Eichhornia crassipes.

PubMed

Pi, N; Ng, J Z; Kelly, B C

2017-12-01

Information regarding the bioaccumulation behaviour of pharmaceutically active compounds (PhACs) and endocrine disrupting chemicals (EDCs) in aquatic plants is limited. The present study involved controlled hydroponic experiments to assess uptake and elimination rate constants (k u , k e ), bioconcentration factors (BCFs) and translocation factors (TFs) of several PhACs and EDCs in two aquatic macrophyte species, including one submerged species (Echinodorus horemanii) and one free-floating species (Eichhornia crassipes). The results revealed that the studied compounds are readily taken up in these aquatic plants. While bioconcentration factors (BCFs) and translocation factors (TFs) of the test compounds varied substantially, no discernible relationship with physicochemical properties such as octanol-water distribution coefficient (D ow ), membrane-water distribution coefficient (D mw ) and organic carbon-water partition coefficient (K oc ). Diphenhydramine and triclosan exhibited the highest degree of uptake and bioaccumulation potential. For example, the whole-plant BCF of triclosan in E. horemanii was 4390L/kg, while the whole-plant BCF of diphenhydramine in E. crassipes was 6130L/kg. BCFs of 17β-estradiol (E2), 17α-ethinylestradiol (EE2), estrone (E1) and bisphenol A (BPA) were relatively low (2-150L/kg). BCFs were generally higher in free-floating aquatic macrophyte species compared to the submerged species. For the free-floating species, E. crassipes, the majority of PhACs and EDCs were more allocated in roots compared to leaves, with TFs<1. However, some compounds such as caffeine, atrazine, diphenhydramine, E2 and carbamazepine were more allocated in leaf tissue (TFs>1). The study findings may be useful for design and implementation of phytoremediation systems, as well as aid future modeling and risk assessment initiatives for these emerging organic contaminants. Copyright © 2017 Elsevier B.V. All rights reserved.

Understanding the potential benefits of thyme and its derived products for food industry and consumer health: From extraction of value-added compounds to the evaluation of bioaccessibility, bioavailability, anti-inflammatory, and antimicrobial activities.

PubMed

Lorenzo, Jose M; Mousavi Khaneghah, Amin; Gavahian, Mohsen; Marszałek, Krystian; Eş, Ismail; Munekata, Paulo E S; Ferreira, Isabel C F R; Barba, Francisco J

2018-05-17

Natural bioactive compounds isolated from several aromatic plants have been studied for centuries due to their unique characteristics that carry great importance in food, and pharmaceutical, and cosmetic industries. For instance, several beneficial activities have been attributed to some specific compounds found in Thymus such as anti-inflammatory, antioxidant, antimicrobial, and antiseptic properties. Moreover, these compounds are classified as Generally Recognized as Safe (GRAS) which means they can be used as an ingrident of may food producs. Conventional extraction processes of these compounds and their derived forms from thyme leaves are well established. Hoewever, they present some important drawbacks such as long extraction time, low yield, high solvent consumption and degradation thermolabile compounds. Therefore, innovative extraction techniques such as ultrasound, microwave, enzyme, ohmic and heat-assisted methods can be useful strategies to enhance the exytraction yield and to reduce processing temperature, extraction time, and energy and solvent consumption. Furthermore, bioaccessibility and bioavailability aspects of these bioactive compounds as well as their metabolic fates are crucial for developing novel functional foods. Additionally, immobilization methods to improve stability, solubility, and the overall bioavailability of these valuable compounds are necessary for their commercial applications. This review aims to give an overall perspective of innovative extraction techniques to extract the targeted compounds with anti-inflammatory and antimicrobial activities. Moreover, the bioaccessi-bility and bioavailability of these compounds before and after processing discussed. In addition, some of the most important characteristics of thyme and their derived products discussed in this paper.

Pharmaceutical compounding or pharmaceutical manufacturing? A regulatory perspective.

PubMed

Timko, Robert J; Crooker, Philip E M

2014-01-01

At one time, nearly all prescriptions were compounded preparations. There is an ongoing demand for compounded prescription medications because manufacturers cannot fulfill the needs of all individual patients. Compounding pharmacies are a long standing yet less frequently discussed element in the complex matrix of prescription drug manufacturing, distribution, and patient use. The drug shortage situation for many necessary and life-saving drug products is a complicating factor that has led to the numerous quality issues that currently plague large-scale compounding pharmacies. The states are the primary regulator of pharmacies, including community drug stores, large chains, and specialty pharmacies. Pharmacies making and distributing drugs in a way that is outside the bounds of traditional pharmacy compounding are of great concern to the U.S. Food and Drug Administration. The U.S. Congress has recently passed the Drug Quality and Security Act. This legislation establishes a clear boundary between traditional compounders and compounding manufacturers. It clarifies a national, uniform set of rules for compounding manufacturers while preserving the states' primary role in traditional pharmacy regulation. It clarifies the U.S. Food and Drug Administration's authority over the compounding of human drugs while requiring the Agency to engage and coordinate with states to ensure the safety of compounded drugs.

Surfactants, Aromatic and Isoprenoid Compounds, and Fatty Acid Biosynthesis Inhibitors Suppress Staphylococcus aureus Production of Toxic Shock Syndrome Toxin 1▿

PubMed Central

McNamara, Peter J.; Syverson, Rae Ellen; Milligan-Myhre, Kathy; Frolova, Olga; Schroeder, Sarah; Kidder, Joshua; Hoang, Thanh; Proctor, Richard A.

2009-01-01

Menstrual toxic shock syndrome is a rare but potentially life-threatening illness manifest through the actions of Staphylococcus aureus toxic shock syndrome toxin 1 (TSST-1). Previous studies have shown that tampon additives can influence staphylococcal TSST-1 production. We report here on the TSST-1-suppressing activity of 34 compounds that are commonly used additives in the pharmaceutical, food, and perfume industries. Many of the tested chemicals had a minimal impact on the growth of S. aureus and yet were potent inhibitors of TSST-1 production. The TSST-1-reducing compounds included surfactants with an ether, amide, or amine linkage to their fatty acid moiety (e.g., myreth-3-myristate, Laureth-3, disodium lauroamphodiacetate, disodium lauramido monoethanolamido, sodium lauriminodipropionic acid, and triethanolamine laureth sulfate); aromatic compounds (e.g. phenylethyl and benzyl alcohols); and several isoprenoids and related compounds (e.g., terpineol and menthol). The membrane-targeting and -altering effects of the TSST-1-suppressing compounds led us to assess the activity of molecules that are known to inhibit fatty acid biosynthesis (e.g., cerulenin, triclosan, and hexachlorophene). These compounds also reduced S. aureus TSST-1 production. This study suggests that more additives than previously recognized inhibit the production of TSST-1. PMID:19223628

Potential exposure to human prescription pharmaceutical residues from wastewater

EPA Science Inventory

Pharmaceuticals in the environment (PiE) pose a complicated problem, involving multiple dissimilar compounds, multiple routes of potential exposure, and a range of potentially affected organisms that span the tree of life. Key uncertainties include not knowing which of the thous...

Characterisation and Antioxidant Activity of Crude Extract and Polyphenolic Rich Fractions from C. incanus Leaves

PubMed Central

Gori, Antonella; Ferrini, Francesco; Marzano, Maria Cristina; Tattini, Massimiliano; Centritto, Mauro; Baratto, Maria Camilla; Pogni, Rebecca; Brunetti, Cecilia

2016-01-01

Cistus incanus (Cistaceae) is a Mediterranean evergreen shrub. Cistus incanus herbal teas have been used as a general remedy in traditional medicine since ancient times. Recent studies on the antioxidant properties of its aqueous extracts have indicated polyphenols to be the most active compounds. However, a whole chemical characterisation of polyphenolic compounds in leaves of Cistus incanus (C. incanus) is still lacking. Moreover, limited data is available on the contribution of different polyphenolic compounds towards the total antioxidant capacity of its extracts. The purpose of this study was to characterise the major polyphenolic compounds present in a crude ethanolic leaf extract (CEE) of C. incanus and develop a method for their fractionation. Superoxide anion, hydroxyl and DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging assays were also performed to evaluate the antioxidant properties of the obtained fractions. Three different polyphenolic enriched extracts, namely EAC (Ethyl Acetate Fraction), AF1 and AF2 (Aqueos Fractions), were obtained from CEE. Our results indicated that the EAC, enriched in flavonols, exhibited a higher antiradical activity compared to the tannin enriched fractions (AF1 and AF2). These findings provide new perspectives for the use of the EAC as a source of antioxidant compounds with potential uses in pharmaceutical preparations. PMID:27548139

Enzymatic synthesis of 1,3-dihydroxyphenylacetoyl-sn-glycerol: Optimization by response surface methodology and evaluation of its antioxidant and antibacterial activities.

PubMed

Kharrat, Nadia; Aissa, Imen; Dgachi, Youssef; Aloui, Fatma; Chabchoub, Fakher; Bouaziz, Mohamed; Gargouri, Youssef

2017-12-01

In this study, the enzymatic synthesis of phenylacetoyl glycerol ester was carried out as a response to the increasing consumer demand for natural compounds. 1,3-dihydroxyphenylacetoyl-sn-Glycerol (1,3-di-HPA-Gly), labeled as "natural" compound with interesting biological properties, has been successfully synthesized for the first time in good yield by a direct esterification of glycerol (Gly) with p-hydroxyphenylacetic acid (p-HPA) using immobilized Candida antarctica lipase as a biocatalyst. Spectroscopic analyses of purified esters showed that the glycerol was mono- or di-esterified on the primary hydroxyl group. These compounds were evaluated for their antioxidant activity using two different tests. The glycerol di-esters (1,3-di-HPA-Gly) showed a higher antiradical capacity than that of the butyl hydroxytoluene. Furthermore, compared to the p-HPA, synthesized ester (1,3-di-HPA-Gly) exhibited the most antibacterial effect mainly against Gram + bacteria. Among synthesized esters the 1,3-di-HPA-Gly was most effective as antioxidant and antibacterial compound. These findings could be the basis for a further exploitation of the new compound, 1,3-di-HPA-Gly, as antioxidant and antibacterial active ingredient in the cosmetic and pharmaceutical fields. Copyright © 2017. Published by Elsevier Inc.

Analysis of Antibacterial Activity and Bioactive Compounds of the Giant Mushroom, Macrocybe gigantea (Agaricomycetes), from India.

PubMed

Gaur, Tanvi; Rao, P B

2017-01-01

The antibacterial activity, phenolic profile, and bioactive compounds of fruiting bodies from 2 strains (MA1 and MA2) of the giant mushroom Macrocybe gigantea were evaluated to access their nutraceutical efficacy. The antibacterial activity was higher in MA2 against all selected pathogenic bacteria. Selected phenolics were analyzed by high-performance liquid chromatography coupled with ultraviolet-visible detection. Gallic acid, ferulic acid, quercetin, p-hydroxy benzoic acid, cinnamic acid, and rutin contents (micrograms per gram dry weight) were quantified. Quercetin and rutin were absent in both strains of M. gigantea. M. gigantea MA2 showed relatively higher phenolic content (915.8 μg/g dry weight) than M. gigantea MA1 (854.4 μg/g dry weight). Among the phenolics, gallic acid is found in the largest amount; in M. gigantea MA2, it was 847.9 ± 2.67 μg/g dry weight. Gas chromatography-mass spectrometry analysis showed the presence of bioactive compounds in both strains; most compounds were antibacterial. Thus, the selected strains of M. gigantea can combat oxidative damage and can be used in foods, pharmaceuticals, and cosmetics because of their antioxidant potential.

Papain-like protease (PLpro) inhibitory effects of cinnamic amides from Tribulus terrestris fruits.

PubMed

Song, Yeong Hun; Kim, Dae Wook; Curtis-Long, Marcus John; Yuk, Heung Joo; Wang, Yan; Zhuang, Ningning; Lee, Kon Ho; Jeon, Kwon Seok; Park, Ki Hun

2014-01-01

Tribulus terrestris fruits are well known for their usage in pharmaceutical preparations and food supplements. The methanol extract of T. terrestris fruits showed potent inhibition against the papain-like protease (PLpro), an essential proteolylic enzyme for protection to pathogenic virus and bacteria. Subsequent bioactivity-guided fractionation of this extract led to six cinnamic amides (1-6) and ferulic acid (7). Compound 6 emerged as new compound possessing the very rare carbinolamide motif. These compounds (1-7) were evaluated for severe acute respiratory syndrome coronavirus (SARS-CoV) PLpro inhibitory activity to identify their potencies and kinetic behavior. Compounds (1-6) displayed significant inhibitory activity with IC50 values in the range 15.8-70.1 µM. The new cinnamic amide 6 was found to be most potent inhibitor with an IC50 of 15.8 µM. In kinetic studies, all inhibitors exhibited mixed type inhibition. Furthermore, the most active PLpro inhibitors (1-6) were proven to be present in the native fruits in high quantities by HPLC chromatogram and liquid chromatography with diode array detection and electrospray ionization mass spectrometry (LC-DAD-ESI/MS).

Occurrence and fate of pharmaceutically active compounds in the largest municipal wastewater treatment plant in Southwest China: mass balance analysis and consumption back-calculated model.

PubMed

Yan, Qing; Gao, Xu; Huang, Lei; Gan, Xiu-Mei; Zhang, Yi-Xin; Chen, You-Peng; Peng, Xu-Ya; Guo, Jin-Song

2014-03-01

The occurrence and fate of twenty-one pharmaceutically active compounds (PhACs) were investigated in different steps of the largest wastewater treatment plant (WWTP) in Southwest China. Concentrations of these PhACs were determined in both wastewater and sludge phases by a high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Results showed that 21 target PhACs were present in wastewater and 18 in sludge. The calculated total mass load of PhACs per capita to the influent, the receiving water and sludge were 4.95mgd(-1)person(-1), 889.94μgd(-1)person(-1) and 78.57μgd(-1)person(-1), respectively. The overall removal efficiency of the individual PhACs ranged from "negative removal" to almost complete removal. Mass balance analysis revealed that biodegradation is believed to be the predominant removal mechanism, and sorption onto sludge was a relevant removal pathway for quinolone antibiotics, azithromycin and simvastatin, accounting for 9.35-26.96% of the initial loadings. However, the sorption of the other selected PhACs was negligible. The overall pharmaceutical consumption in Chongqing, China, was back-calculated based on influent concentration by considering the pharmacokinetics of PhACs in humans. The back-estimated usage was in good agreement with usage of ofloxacin (agreement ratio: 72.5%). However, the back-estimated usage of PhACs requires further verification. Generally, the average influent mass loads and back-calculated annual per capita consumption of the selected antibiotics were comparable to or higher than those reported in developed countries, while the case of other target PhACs was opposite. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of radical scavenging activity, intestinal cell viability and antifungal activity of Brazilian propolis by-product.

PubMed

de Francisco, Lizziane; Pinto, Diana; Rosseto, Hélen; Toledo, Lucas; Santos, Rafaela; Tobaldini-Valério, Flávia; Svidzinski, Terezinha; Bruschi, Marcos; Sarmento, Bruno; Oliveira, M Beatriz P P; Rodrigues, Francisca

2018-03-01

Propolis is a natural adhesive resinous compound produced by honeybees to protect hives from bacteria and fungi, being extremely expensive for food industry. During propolis production, a resinous by-product is formed. This resinous waste is currently undervalued and underexploited. Accordingly, in this study the proximate physical and chemical quality, as well as the antioxidant activity, radical scavenging activity and cell viability of this by-product were evaluated and compared with propolis in order to boost new applications in food and pharmaceutical industries. The results revealed that the by-product meets the physical and chemical quality standards expected and showed that the propolis waste contains similar amounts of total phenolic content (TPC) and total flavonoid content (TFC) to propolis. Also, a good scavenging activity against reactive oxygen and nitrogen species (ROS and RNS, respectively) determined by the assays of superoxide anion radical (O 2 - ), hydrogen peroxide (H 2 O 2 ), hypochlorous acid (HOCl), nitric oxide (NO) and peroxyl radical (ROO) were determined. Linear positive correlations were established between the TPC of both samples and the antioxidant activity evaluated by three different methods (DPPH, ABTS and FRAP assays). The extracts were also screened for cell viability assays in two different intestinal cell lines (HT29-MTX and Caco-2), showing a viability concentration-dependent. Similarly, the Artemia salina assay, used to assess toxicity, demonstrated the concentration influence on results. Finally, the antifungal activity against ATCC species of Candida was demonstrated. These results suggest that propolis by-product can be used as a new rich source of bioactive compounds for different areas, such as food or pharmaceutical. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using ultraviolet absorbance and color to assess pharmaceutical oxidation during ozonation of wastewater.

PubMed

Wert, Eric C; Rosario-Ortiz, Fernando L; Snyder, Shane A

2009-07-01

The reduction of ultraviolet (UV) absorbance at 254 nm (UV254) and true color were identified as appropriate surrogates to assess the oxidation of six pharmaceuticals (i.e., carbamazepine, meprobamate, dilantin, primidone, atenolol, and iopromide) during ozonation of wastewater. Three tertiary-treated wastewaters were evaluated during oxidation with ozone (O3) and O3 coupled with hydrogen peroxide (O3/H2O2). The correlation between pharmaceutical oxidation and removal of UV254 was dependent upon the reactivity of each specific compound toward ozone, as measured by the second-order rate constant (k'(O3)). Oxidation of compounds with k'(O3) > 10(3) M(-1) s(-1) correlated well (R2 > 0.73) with UV254 reduction between 0-50%. Oxidation of compounds with apparent k'(O3) < 10 M(-1) s(-1) resulted primarily from hydroxyl radicals and correlated well (R2 > 0.80) with the UV254 reduction of 15-85%. The removal of true color also correlated well (R2 > 0.85) with the oxidation of pharmaceuticals during the ozonation of two wastewaters. These correlations demonstrate that UV254 reduction and true color removal may be used as surrogates to evaluate pharmaceutical oxidation in the presence or absence of dissolved ozone residual during advanced wastewater treatment with O3 or O3/H2O2. The use of online UV254 measurements would allow wastewater utilities to optimize the ozone dose required to meet their specific treatment objectives.

Effects of acetylacetone on the photoconversion of pharmaceuticals in natural and pure waters.

PubMed

Zhang, Guoyang; Wu, Bingdang; Zhang, Shujuan

2017-06-01

Acetylacetone (AcAc) has proven to be a potent photo-activator in the degradation of color compounds. The effects of AcAc on the photochemical conversion of five colorless pharmaceuticals were for the first time investigated in both pure and natural waters with the UV/H 2 O 2 process as a reference. In most cases, AcAc played a similar role to H 2 O 2 . For example, AcAc accelerated the photodecomposition of carbamazepine, oxytetracycline, and tetracycline in pure water. Meanwhile, the toxicity of tetracyclines and carbamazepine were reduced to a similar extent to that in the UV/H 2 O 2 process. However, AcAc worked in a way different from that of H 2 O 2 . Based on the degradation kinetics, solvent kinetic isotope effect, and the inhibiting effect of O 2 , the underlying mechanisms for the degradation of pharmaceuticals in the UV/AcAc process were believed mainly to be direct energy transfer from excited AcAc to pharmaceuticals rather than reactive oxygen species-mediated reactions. In natural waters, dissolved organic matter (DOM) played a crucial role in the photoconversion of pharmaceuticals. The role of H 2 O 2 became negligible due to the scavenging effects of DOM and inorganic ions. Interestingly, in natural waters, AcAc first accelerated the photodecomposition of pharmaceuticals and then led to a dramatic reduction with the depletion of dissolved oxygen. Considering the natural occurrence of diketones, the results here point out a possible pathway in the fate and transport of pharmaceuticals in aquatic ecosystems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Temporal and spatial variation in pharmaceutical concentrations in an urban river system

USGS Publications Warehouse

Burns, Emily E.; Carter, Laura J.; Kolpin, Dana W.; Thomas-Oates, Jane; Boxall, Alistair B.A.

2018-01-01

Many studies have quantified pharmaceuticals in the environment, few however, have incorporated detailed temporal and spatial variability due to associated costs in terms of time and materials. Here, we target 33 physico-chemically diverse pharmaceuticals in a spatiotemporal exposure study into the occurrence of pharmaceuticals in the wastewater system and the Rivers Ouse and Foss (two diverse river systems) in the city of York, UK. Removal rates in two of the WWTPs sampled (a conventional activated sludge (CAS) and trickling filter plant) ranged from not eliminated (carbamazepine) to >99% (paracetamol). Data comparisons indicate that pharmaceutical exposures in river systems are highly variable regionally, in part due to variability in prescribing practices, hydrology, wastewater management, and urbanisation and that select annual median pharmaceutical concentrations observed in this study were higher than those previously observed in the European Union and Asia thus far. Significant spatial variability was found between all sites in both river systems, while seasonal variability was significant for 86% and 50% of compounds in the River Foss and Ouse, respectively. Seasonal variations in flow, in-stream attenuation, usage and septic effluent releases are suspected drivers behind some of the observed temporal exposure variability. When the data were used to evaluate a simple environmental exposure model for pharmaceuticals, mean ratios of predicted environmental concentrations (PECs), obtained using the model, to measured environmental concentrations (MECs) were 0.51 and 0.04 for the River Foss and River Ouse, respectively. Such PEC/MEC ratios indicate that the model underestimates actual concentrations in both river systems, but to a much greater extent in the larger River Ouse.

Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer

DTIC Science & Technology

2015-10-01

BGJ398; Novartis Pharmaceuticals ), is the lead compound being tested as anticancer therapy by Novartis. In addition, in an agreement with Janssen... Pharmaceutical Companies of Johnson & Johnson we obtained a pan-FGFR inhibitor from (JNJS 42756493) to test in a preclinical setting. For this...10ml/kg x BID) according to Janssen Pharmaceutical instructions. Treatment started 10 days after cell injection. After 3 weeks of treatment, we

When to Compound Medications for Veterinary Patients.

PubMed

Forsythe, Lauren Eichstadt

2017-01-01

This article serves as a brief discussion about some of the restrictions applicable to compounding medications for veterinary patients based on U. S. Food and Drug Administration compliance policy guidelines and provides a brief summary of when it is appropriate to compound medications for veterinary patients. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Bioactivities from Marine Algae of the Genus Gracilaria

PubMed Central

de Almeida, Cynthia Layse F.; Falcão, Heloina de S.; Lima, Gedson R. de M.; Montenegro, Camila de A.; Lira, Narlize S.; de Athayde-Filho, Petrônio F.; Rodrigues, Luis C.; de Souza, Maria de Fátima V.; Barbosa-Filho, José M.; Batista, Leônia M.

2011-01-01

Seaweeds are an important source of bioactive metabolites for the pharmaceutical industry in drug development. Many of these compounds are used to treat diseases like cancer, acquired immune-deficiency syndrome (AIDS), inflammation, pain, arthritis, as well as viral, bacterial, and fungal infections. This paper offers a survey of the literature for Gracilaria algae extracts with biological activity, and identifies avenues for future research. Nineteen species of this genus that were tested for antibacterial, antiviral, antifungal, antihypertensive, cytotoxic, spermicidal, embriotoxic, and anti-inflammatory activities are cited from the 121 references consulted. PMID:21845096

Layered Structure and Swelling Behavior of a Multiple Hydrate-Forming Pharmaceutical Compound

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiang, Y.; Xu, W; Stephens, P

2009-01-01

Investigation of one anhydrous and four hydrated forms of a pharmaceutical compound (1) using both single-crystal and high-resolution powder X-ray diffraction methods revealed a two-dimensional framework which, upon exposure to moisture, absorbed water between the layers, causing the lattice to expand by as much as 20% of the axial length along a. The single-crystal structure was solved and refined for the pentahydrate form in space group C2 with unit cell parameters a = 36.961(5) Angstroms, b = 7.458(2) Angstroms, c = 20.691(4) Angstroms, e = 99.461(1), and V = 5626(4) Angstroms3. In the single-crystal structure the water layers were parallelmore » to the bc plane and sandwiched by the crystalline compound 1 framework. Upon a change of relative humidity, water goes in and out of the interlayer space with the retention of the layer structure of the development compound. Starting from the anhydrous form, each additional water of hydration increased the interlayer spacing of the pharmaceutical solid by 1.3 Angstroms, half the size of a water molecule. In an exploratory formulation, this expansion of interlayer spacing caused tablets to crack upon storage at high relative humidity.« less

Reconnaissance of Pharmaceutical Chemicals in Urban Streams of the Tualatin River Basin, Oregon, 2002

USGS Publications Warehouse

Rounds, Stewart A.; Doyle, Micelis C.; Edwards, Patrick M.; Furlong, Edward T.

2009-01-01

A reconnaissance of pharmaceutical chemicals in urban streams of the Tualatin River basin was conducted in July 2002 in an effort to better understand the occurrence and distribution of such compounds, and to determine whether they might be useful indicators of human-related stream contamination. Of the 21 pharmaceutical chemicals and metabolites tested, only 6 (acetaminophen, caffeine, carbamazepine, codeine, cotinine, and sulfamethoxazole) were detected in filtered stream samples from 10 sites. The concentrations of most of the detected compounds were relatively low (less than 0.05 microgram per liter). The most frequently detected compounds were cotinine (a nicotine metabolite, 8 of 10 samples) and caffeine (a stimulant, 7 of 10 samples). More compounds were detected in urban stream samples than in samples from forested or agricultural drainages. Filtered water samples also were collected from four locations within an advanced wastewater treatment facility to quantify the relative amounts of these chemicals in a municipal waste stream and to determine the degree to which those chemicals are removed by treatment processes. Fifteen pharmaceutical chemicals or metabolites were detected in wastewater treatment facility influent, with concentrations far exceeding those measured in streams. Only five of those compounds, however, were detected in the treated effluent (carbamazepine, cotinine, ibuprofen, metformin, and sulfamethoxazole) and most of those were at concentrations less than 0.2 microgram per liter. The target pharmaceutical chemicals and metabolites showed limited potential for use as tracers of specific types of human-related contamination in Tualatin River basin streams because of widespread sources (caffeine, for example) or extremely low concentrations. Caffeine and cotinine are likely to be good indicators of sources that can occur in urban areas, such as sewage spills or leaks or the widespread use and careless disposal of tobacco products and caffeine-containing beverages. Neither compound, however, is likely to be a good tracer for a specific source unless that source is large. The presence of 1,7-dimethylxanthine (a caffeine metabolite) concurrently with caffeine might indicate the presence of untreated wastewater; in contrast, the absence of the metabolite might help rule out that source. Acetaminophen might make a good tracer for untreated wastewater because of its common usage, high concentration in raw wastewater, and effective removal via treatment. Carbamazepine and sulfamethoxazole have the potential to be good indicators of treated wastewater because of their incomplete removal in treatment facilities. Some of these pharmaceutical chemicals, either singly or in combination, might prove useful as tracers of contamination after further study.

Placental ABC Transporters: Biological Impact and Pharmaceutical Significance.

PubMed

Joshi, Anand A; Vaidya, Soniya S; St-Pierre, Marie V; Mikheev, Andrei M; Desino, Kelly E; Nyandege, Abner N; Audus, Kenneth L; Unadkat, Jashvant D; Gerk, Phillip M

2016-12-01

The human placenta fulfills a variety of essential functions during prenatal life. Several ABC transporters are expressed in the human placenta, where they play a role in the transport of endogenous compounds and may protect the fetus from exogenous compounds such as therapeutic agents, drugs of abuse, and other xenobiotics. To date, considerable progress has been made toward understanding ABC transporters in the placenta. Recent studies on the expression and functional activities are discussed. This review discusses the placental expression and functional roles of several members of ABC transporter subfamilies B, C, and G including MDR1/P-glycoprotein, the MRPs, and BCRP, respectively. Since placental ABC transporters modulate fetal exposure to various compounds, an understanding of their functional and regulatory mechanisms will lead to more optimal medication use when necessary in pregnancy.

Placental ABC Transporters: Biological Impact and Pharmaceutical Significance

PubMed Central

Joshi, Anand A.; Vaidya, Soniya S.; St-Pierre, Marie V.; Mikheev, Andrei M.; Desino, Kelly E.; Nyandege, Abner N.; Audus, Kenneth L.; Unadkat, Jashvant D.; Gerk, Phillip M.

2017-01-01

The human placenta fulfills a variety of essential functions during prenatal life. Several ABC transporters are expressed in the human placenta, where they play a role in the transport of endogenous compounds and may protect the fetus from exogenous compounds such as therapeutic agents, drugs of abuse, and other xenobiotics. To date, considerable progress has been made toward understanding ABC transporters in the placenta. Recent studies on the expression and functional activities are discussed. This review discusses the placental expression and functional roles of several members of ABC transporter subfamilies B, C, and G including MDR1/P-glycoprotein, the MRPs, and BCRP, respectively. Since placental ABC transporters modulate fetal exposure to various compounds, an understanding of their functional and regulatory mechanisms will lead to more optimal medication use when necessary in pregnancy. PMID:27644937

Pharmaceuticals and Related Drugs.

ERIC Educational Resources Information Center

Gilpin, R. K.; Pachla, L. A.

1989-01-01

This review is divided into these topics: alkaloids, antibiotics, inorganics, nitrogen and oxygen containing compounds, steroids, sulfur containing compounds, vitamins, techniques, and miscellaneous methods. The review covers from November 1986, to October 1988. (MVL)

Predicting targets of compounds against neurological diseases using cheminformatic methodology

NASA Astrophysics Data System (ADS)

Nikolic, Katarina; Mavridis, Lazaros; Bautista-Aguilera, Oscar M.; Marco-Contelles, José; Stark, Holger; do Carmo Carreiras, Maria; Rossi, Ilaria; Massarelli, Paola; Agbaba, Danica; Ramsay, Rona R.; Mitchell, John B. O.

2015-02-01

Recently developed multi-targeted ligands are novel drug candidates able to interact with monoamine oxidase A and B; acetylcholinesterase and butyrylcholinesterase; or with histamine N-methyltransferase and histamine H3-receptor (H3R). These proteins are drug targets in the treatment of depression, Alzheimer's disease, obsessive disorders, and Parkinson's disease. A probabilistic method, the Parzen-Rosenblatt window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Molecular structures were represented based on the circular fingerprint methodology. The same approach was used to build a "predictor" model from the DrugBank dataset to determine the main pharmacological groups of the compound. The study of off-target interactions is now recognised as crucial to the understanding of both drug action and toxicology. Primary pharmaceutical targets and off-targets for the novel multi-target ligands were examined by use of the developed cheminformatic method. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. The cheminformatic targets identifications were in agreement with four 3D-QSAR (H3R/D1R/D2R/5-HT2aR) models and by in vitro assays for serotonin 5-HT1a and 5-HT2a receptor binding of the most promising ligand ( 71/MBA-VEG8).

Identifying and assessing highly hazardous drugs within quality risk management programs.

PubMed

Sussman, Robert G; Schatz, Anthony R; Kimmel, Tracy A; Ader, Allan; Naumann, Bruce D; Weideman, Patricia A

2016-08-01

Historically, pharmaceutical industry regulatory guidelines have assigned certain active pharmaceutical ingredients (APIs) to various categories of concern, such as "cytotoxic", "hormones", and "steroids". These categories have been used to identify APIs requiring segregation or dedication in order to prevent cross-contamination and protect the quality and safety of drug products. Since these terms were never defined by regulatory authorities, and many novel pharmacological mechanisms challenge these categories, there is a recognized need to modify the historical use of these terms. The application of a risk-based approach using a health-based limit, such as an acceptable daily exposure (ADE), is more appropriate for the development of a Quality Risk Management Program (QRMP) than the use of categories of concern. The toxicological and pharmacological characteristics of these categories are discussed to help identify and prioritize compounds requiring special attention. Controlling airborne concentrations and the contamination of product contact surfaces in accordance with values derived from quantitative risk assessments can prevent adverse effects in workers and patients, regardless of specific categorical designations to which these APIs have been assigned. The authors acknowledge the movement away from placing compounds into categories and, while not yet universal, the importance of basing QRMPs on compound-specific ADEs and risk assessments. Based on the results of a risk assessment, segregation and dedication may also be required for some compounds to prevent cross contamination during manufacture of APIs. Copyright © 2016 Elsevier Inc. All rights reserved.

Metabolite profiling and isolation of biologically active compounds from Scadoxus puniceus, a highly traded South African medicinal plant.

PubMed

Naidoo, Devashan; Slavětínská, Lenka Poštová; Aremu, Adeyemi O; Gruz, Jiri; Biba, Ondrej; Doležal, Karel; Van Staden, Johannes; Finnie, Jeffrey F

2018-04-01

Scadoxus puniceus (Amaryllidaceae), a medicinal plant of high value in South Africa, is used as a component of a traditional herbal tonic prescribed to treat several ailments. Ultra-high performance liquid chromatography-tandem mass spectrometry quantified the phenolic compounds in different organs of S. puniceus. Gravity column chromatography was used to separate fractions and active compounds. The structure of these compounds was determined using 1D and 2D nuclear magnetic resonance and mass spectroscopic techniques. A microplate technique was used to determine the acetylcholinesterase inhibitory activity of the pure compounds. Metabolite profiling revealed a greater profusion of hydroxycinnamic acids (69.5%), as opposed to hydroxybenzoic acids (30.5%). Chlorogenic acid was the most abundant (49.6% of hydroxycinnamic acids) compound. In addition to chlorogenic acid, the study is the first to report the presence of sinapic, gallic, and m-hydroxybenzoic acids in the Amaryllidaceae. Chromatographic separation of S. puniceus led to the isolation of haemanthamine (1), haemanthidine (2), and a rare chlorinated amide, metolachlor (3), the natural occurrence of which is described for the first time. Haemanthamine, haemanthidine, and metolachlor displayed strong acetylcholinesterase inhibitory activity (IC 50 ; 23.1, 23.7, and 11.5 μM, respectively). These results substantiate the frequent use of S. puniceus as a medicinal plant and hold much promise for further pharmaceutical development. Copyright © 2017 John Wiley & Sons, Ltd.

Prospective Source of Antimicrobial Compounds From Pigment Produced by Bacteria associated with Brown Alga ( Phaeophyceae ) Isolated from Karimunjawa island, Indonesia

NASA Astrophysics Data System (ADS)

Lunggani, A. T.; Darmanto, Y. S.; Radjasa, O. K.; Sabdono, A.

2018-02-01

Brown algae or Phaeophyceae characterized by their natural pigments that differ from other important algal classes. Several publications proves that brown algae - associated bacteria have great potential in developing marine pharmaceutical industry since they are capable to synthesized numerous bioactive metabolite compounds. However the potency of marine pigmented microbes associated with brown alga to produce natural pigments and antimicrobials has been less studied. Marine pigmented bacteria associated with brown algae collected from Karimunjawa Island were successfully isolated and screened for antimicrobial activity. The aim of this research was evaluated of the antimicrobial activity of pigments extracted from culturable marine pigmented bacteria on some pathogenic bacteria and yeast. The results showed that all isolates had antimicrobial activity and could be prospectively developed as antimicrobial agent producing pigments. The 6 marine pigmented bacteria was identified to genus level as Pseudoalteromonas, Sphingomonas, Serratia, Paracoccus, Vibrio.

Mannich Bases: An Important Pharmacophore in Present Scenario

PubMed Central

Sharma, Neha; Kajal, Anu; Saini, Vipin

2014-01-01

Mannich bases are the end products of Mannich reaction and are known as beta-amino ketone carrying compounds. Mannich reaction is a carbon-carbon bond forming nucleophilic addition reaction and is a key step in synthesis of a wide variety of natural products, pharmaceuticals, and so forth. Mannich reaction is important for the construction of nitrogen containing compounds. There is a number of aminoalkyl chain bearing Mannich bases like fluoxetine, atropine, ethacrynic acid, trihexyphenidyl, and so forth with high curative value. The literature studies enlighten the fact that Mannich bases are very reactive and recognized to possess potent diverse activities like anti-inflammatory, anticancer, antifilarial, antibacterial, antifungal, anticonvulsant, anthelmintic, antitubercular, analgesic, anti-HIV, antimalarial, antipsychotic, antiviral activities and so forth. The biological activity of Mannich bases is mainly attributed to α, β-unsaturated ketone which can be generated by deamination of hydrogen atom of the amine group. PMID:25478226

GC-MS characterization of n-hexane soluble fraction from dandelion (Taraxacum officinale Weber ex F.H. Wigg.) aerial parts and its antioxidant and antimicrobial properties.

PubMed

Ivanov, Ivan; Petkova, Nadezhda; Tumbarski, Julian; Dincheva, Ivayla; Badjakov, Ilian; Denev, Panteley; Pavlov, Atanas

2018-01-26

A comparative investigation of n-hexane soluble compounds from aerial parts of dandelion (Taraxacum officinale Weber ex F.H. Wigg.) collected during different vegetative stages was carried out. The GC-MS analysis of the n-hexane (unpolar) fraction showed the presence of 30 biologically active compounds. Phytol [14.7% of total ion current (TIC)], lupeol (14.5% of TIC), taraxasteryl acetate (11.4% of TIC), β-sitosterol (10.3% of TIC), α-amyrin (9.0% of TIC), β-amyrin (8.3% of TIC), and cycloartenol acetate (5.8% of TIC) were identified as the major components in n-hexane fraction. The unpolar fraction exhibited promising antioxidant activity - 46.7 mmol Trolox equivalents/g extract (determined by 1,1-diphenyl-2-picrylhydrazyl method). This fraction demonstrated insignificant antimicrobial activity and can be used in cosmetic and pharmaceutical industries.

Attenuation of pharmaceuticals and their transformation products in a wastewater treatment plant and its receiving river ecosystem.

PubMed

Aymerich, I; Acuña, V; Barceló, D; García, M J; Petrovic, M; Poch, M; Rodriguez-Mozaz, S; Rodríguez-Roda, I; Sabater, S; von Schiller, D; Corominas, Ll

2016-09-01

Pharmaceuticals are designed to improve human and animal health, but may also be a threat to freshwater ecosystems, particularly after receiving urban or wastewater treatment plant (WWTP) effluents. Knowledge on the fate and attenuation of pharmaceuticals in engineered and natural ecosystems is rather fragmented, and comparable methods are needed to facilitate the comprehension of those processes amongst systems. In this study the dynamics of 8 pharmaceuticals (acetaminophen, sulfapyridine, sulfamethoxazole, carbamazepine, venlafaxine, ibuprofen, diclofenac, diazepam) and 11 of their transformation products were investigated in a WWTP and the associated receiving river ecosystem. During 3 days, concentrations of these compounds were quantified at the influents, effluents, and wastage of the WWTP, and at different distances downstream the effluent at the river. Attenuation (net balance between removal and release from and to the water column) was estimated in both engineered and natural systems using a comparable model-based approach by considering different uncertainty sources (e.g. chemical analysis, sampling, and flow measurements). Results showed that pharmaceuticals load reduction was higher in the WWTP, but attenuation efficiencies (as half-life times) were higher in the river. In particular, the load of only 5 out of the 19 pharmaceuticals was reduced by more than 90% at the WWTP, while the rest were only partially or non-attenuated (or released) and discharged into the receiving river. At the river, only the load of ibuprofen was reduced by more than 50% (out of the 6 parent compounds present in the river), while partial and non-attenuation (or release) was observed for some of their transformation products. Linkages in the routing of some pharmaceuticals (venlafaxine, carbamazepine, ibuprofen and diclofenac) and their corresponding transformation products were also identified at both WWTP and river. Finally, the followed procedure showed that dynamic attenuation in the coupled WWTP-river system could be successfully predicted with simple first order attenuation kinetics for most modeled compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antimicrobial compounds from seaweeds-associated bacteria and fungi.

PubMed

Singh, Ravindra Pal; Kumari, Puja; Reddy, C R K

2015-02-01

In recent decade, seaweeds-associated microbial communities have been significantly evaluated for functional and chemical analyses. Such analyses let to conclude that seaweeds-associated microbial communities are highly diverse and rich sources of bioactive compounds of exceptional molecular structure. Extracting bioactive compounds from seaweed-associated microbial communities have been recently increased due to their broad-spectrum antimicrobial activities including antibacterial, antifungal, antiviral, anti-settlement, antiprotozoan, antiparasitic, and antitumor. These allelochemicals not only provide protection to host from other surrounding pelagic microorganisms, but also ensure their association with the host. Antimicrobial compounds from marine sources are promising and priority targets of biotechnological and pharmaceutical applications. This review describes the bioactive metabolites reported from seaweed-associated bacterial and fungal communities and illustrates their bioactivities. Biotechnological application of metagenomic approach for identifying novel bioactive metabolites is also dealt, in view of their future development as a strong tool to discover novel drug targets from seaweed-associated microbial communities.

Concentration and risk of pharmaceuticals in freshwater systems are related to the population density and the livestock units in Iberian Rivers.

PubMed

Osorio, Victoria; Larrañaga, Aitor; Aceña, Jaume; Pérez, Sandra; Barceló, Damià

2016-01-01

Considerable amounts of pharmaceuticals are used in human and veterinary medicine, which are not efficiently removed during wastewater and slurries treatment and subsequently entering continuously into freshwater systems. The intrinsic biological activity of these non-regulated pollutants turns their presence in the aquatic environment into an ecological matter of concern. We present the first quantitative study relating the presence of pharmaceuticals and their predicted ecotoxicological effects with human population and livestock units. Four representative Iberian River basins (Spain) were studied: Llobregat, Ebro, Júcar and Guadalquivir. The levels of pharmaceuticals were determined in surface water and sediment samples collected from 77 locations along their stream networks. Predicted total toxic units to algae, Daphnia and fish were estimated for pharmaceuticals detected in surface waters. The use of chemometrics enabled the study of pharmaceuticals for: their spatial distribution along the rivers in two consecutive years; their potential ecotoxicological risk to aquatic organisms; and the relationships among their occurrence and predicted ecotoxicity with human population and animal farming pressure. The Llobregat and the Ebro River basins were characterized as the most polluted and at highest ecotoxicological risk, followed by Júcar and Guadalquivir. No significant acute risks of pharmaceuticals to aquatic organisms were observed. However potential chronic ecotoxicological effects on algae could be expected at two hot spots of pharmaceuticals pollution identified in the Llobregat and Ebro basins. Analgesics/antiinflammatories, antibiotics and diuretics were the most relevant therapeutic groups across the four river basins. Among them, hydrochlorothiazide and gemfibrozil, as well as azithromycin and ibuprofen were widely spread and concentrated pharmaceuticals in surface waters and sediments, respectively. Regarding their predicted ecotoxicity, sertraline, gemfibrozil and loratidine were identified as the more concerning compounds. Significantly positive relationships were found among levels of pharmaceuticals and toxic units and population density and livestock units in both surface water and sediment matrices. Copyright © 2015. Published by Elsevier B.V.

Controlled field evaluation of water flow rate effects on sampling polar organic compounds using polar organic chemical integrative samplers.

PubMed

Li, Hongxia; Vermeirssen, Etiënne L M; Helm, Paul A; Metcalfe, Chris D

2010-11-01

The uptake of polar organic contaminants into polar organic chemical integrative samplers (POCIS) varies with environmental factors, such as water flow rate. To evaluate the influence of water flow rate on the uptake of contaminants into POCIS, flow-controlled field experiments were conducted with POCIS deployed in channel systems through which treated sewage effluent flowed at rates between 2.6 and 37 cm/s. Both pharmaceutical POCIS and pesticide POCIS were exposed to effluent for 21 d and evaluated for uptake of pharmaceuticals and personal care products (PPCPs) and endocrine disrupting substances (EDS). The pesticide POCIS had higher uptake rates for PPCPs and EDS than the pharmaceutical POCIS, but there are some practical advantages to using pharmaceutical POCIS. The uptake of contaminants into POCIS increased with flow rate, but these effects were relatively small (i.e., less than twofold) for most of the test compounds. There was no relationship observed between the hydrophobicity (log octanol/water partition coefficient, log K(OW)) of model compounds and the effects of flow rate on the uptake kinetics by POCIS. These data indicate that water flow rate has a relatively minor influence on the accumulation of PPCPs and EDS into POCIS. © 2010 SETAC.

Biotechnological and industrial significance of cyanobacterial secondary metabolites.

PubMed

Rastogi, Rajesh P; Sinha, Rajeshwar P

2009-01-01

Cyanobacteria are considered to be a rich source of novel metabolites of a great importance from a biotechnological and industrial point of view. Some cyanobacterial secondary metabolites (CSMs), exhibit toxic effects on living organisms. A diverse range of these cyanotoxins may have ecological roles as allelochemicals, and could be employed for the commercial development of compounds with applications such as algaecides, herbicides and insecticides. Recently, cyanobacteria have become an attractive source of innovative classes of pharmacologically active compounds showing interesting and exciting biological activities ranging from antibiotics, immunosuppressant, and anticancer, antiviral, antiinflammatory to proteinase-inhibiting agents. A different but not less interesting property of these microorganisms is their capacity of overcoming the toxicity of ultraviolet radiation (UVR) by means of UV-absorbing/screening compounds, such as mycosporine-like amino acids (MAAs) and scytonemin. These last two compounds are true 'multipurpose' secondary metabolites and considered to be natural photoprotectants. In this sense, they may be biotechnologically exploited by the cosmetic industry. Overall CSMs are striking targets in biotechnology and biomedical research, because of their potential applications in agriculture, industry, and especially in pharmaceuticals.

A Comprehensive Review on Pharmacotherapeutics of Herbal Bioenhancers

PubMed Central

Dudhatra, Ghanshyam B.; Mody, Shailesh K.; Awale, Madhavi M.; Patel, Hitesh B.; Modi, Chirag M.; Kumar, Avinash; Kamani, Divyesh R.; Chauhan, Bhavesh N.

2012-01-01

In India, Ayurveda has made a major contribution to the drug discovery process with new means of identifying active compounds. Recent advancement in bioavailability enhancement of drugs by compounds of herbal origin has produced a revolutionary shift in the way of therapeutics. Thus, bibliographic investigation was carried out by analyzing classical text books and peer-reviewed papers, consulting worldwide-accepted scientific databases from last 30 years. Herbal bioenhancers have been shown to enhance bioavailability and bioefficacy of different classes of drugs, such as antibiotics, antituberculosis, antiviral, antifungal, and anticancerous drugs at low doses. They have also improved oral absorption of nutraceuticals like vitamins, minerals, amino acids, and certain herbal compounds. Their mechanism of action is mainly through absorption process, drug metabolism, and action on drug target. This paper clearly indicates that scientific researchers and pharmaceutical industries have to give emphasis on experimental studies to find out novel active principles from such a vast array of unexploited plants having a role as a bioavailability and bioefficacy enhancer. Also, the mechanisms of action by which bioenhancer compounds exert bioenhancing effects remain to be explored. PMID:23028251

Developing an Activity and Absorption-based Quality Control Platform for Chinese Traditional Medicine: Application to Zeng-Sheng-Ping

PubMed Central

Yin, Taijun; Yang, Guanyi; Ma, Yong; Xu, Beibei; Hu, Ming; You, Ming; Gao, Song

2015-01-01

Ethnopharmacological relevance Zeng-Sheng-Ping (ZSP) is a marketed Chinese traditional medicine used for cancer prevention. Aim of the study Currently, for the quality control of Chinese traditional medicines, marker compounds are not selected based on bioactivities and pharmaceutical behaviors in most of the cases. Therefore, even if the “quality” of the medicine is controlled, the pharmacological effect could still be inconsistent. The aim of this study is to establish an activity and absorption-based platform to select marker compound(s) for the quality control of Chinese traditional medicines. Materials and methods We used ZSP as a reference Chinese traditional medicine to establish the platform. Activity guided fractionation approach was used to purify the major components from ZSP. NMR and MS spectra were used to elucidate the structure of the isolated compounds. MTT assay against oral carcinoma cell line (SCC2095) was performed to evaluate the activities. UPLC-MS/MS was used to quantify the pure compounds in ZSP and the active fraction. The permeabilities of the identified compounds were evaluated in the Caco-2 cell culture model. The intracellular accumulation of the isolated compounds was evaluated in the SCC2095 cells. Results The major compounds were identified from ZSP. The contents, anti-proliferation activities, permeabilities, and intracellular accumulations of these compounds were also evaluated. The structure of these purified compounds were identified by comparing the NMR and MS data with those of references as rutaevine (1), limonin (2) , evodol (3), obacunone (4), fraxinellone (5), dictamnine (6), maackiain (7), trifolirhizin (8), and matrine (9). The IC50 of compounds 5, 6, and 7 against SCC2095 cells were significantly lower than that of ZSP. The uptake permeability of compounds 5, 6, and 7 were 2.58 ± 0. 3 × 10−5, 4.33 ± 0.5 × 10−5, and 4.27 ± 0.8 × 10−5 respectively in the Caco-2 cell culture model. The intracellular concentrations of these compounds showed that compounds 5, 6, and 7 were significantly accumulated inside the cells. Conclusion Based on the activity against oral carcinoma cell line as well as the absorption permeability, compound 5, 6, and 7 are selected as quality control markers for ZSP. A activity and absorption-based platform was established and successfully used for the quality control of ZSP. PMID:26099633

Pharmaceuticals, hormones, anthropogenic waste indicators, and total estrogenicity in liquid and solid samples from municipal sludge stabilization and dewatering

USGS Publications Warehouse

Furlong, Edward T.; Gray, James L.; Quanrud, David M.; Teske, Sondra S.; Werner, Stephen L.; Esposito, Kathleen; Marine, Jeremy; Ela, Wendell P.; Zaugg, Steven D.; Phillips, Patrick J.; Stinson, Beverley

2012-01-01

The ubiquitous presence of pharmaceuticals and other emerging contaminants, or trace organic compounds, in surface water has resulted in research and monitoring efforts to identify contaminant sources to surface waters and to better understand loadings from these sources. Wastewater treatment plant discharges have been identified as an important point source of trace organic compounds to surface water and understanding the transport and transformation of these contaminants through wastewater treatment process is essential to controlling their introduction to receiving waters.

Basics of Compounding: 3D Printing--Pharmacy Applications, Part 1.

PubMed

Allen, Loyd V

2017-01-01

Three-dimensional printing quickly became a standard tool in the automotive, aerospace, and consumer goods industries and, recently, has begun gaining traction in pharmaceutical manufacturing. 3D printing has steadily grown, introducing a new element into dosage form development, and has received a boost with U.S. Food and Drug Administration (FDA) approval of the 3D-printed orodispersible tablet, Spritam (levetiracetam). This part 1 of a 3-part article introduces 3D printing and its application to pharmacy. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Modern Approaches for Asymmetric Construction of Carbon-Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs.

PubMed

Zhu, Yi; Han, Jianlin; Wang, Jiandong; Shibata, Norio; Sodeoka, Mikiko; Soloshonok, Vadim A; Coelho, Jaime A S; Toste, F Dean

2018-04-11

New methods for preparation of tailor-made fluorine-containing compounds are in extremely high demand in nearly every sector of chemical industry. The asymmetric construction of quaternary C-F stereogenic centers is the most synthetically challenging and, consequently, the least developed area of research. As a reflection of this apparent methodological deficit, pharmaceutical drugs featuring C-F stereogenic centers constitute less than 1% of all fluorine-containing medicines currently on the market or in clinical development. Here we provide a comprehensive review of current research activity in this area, including such general directions as asymmetric electrophilic fluorination via organocatalytic and transition-metal catalyzed reactions, asymmetric elaboration of fluorine-containing substrates via alkylations, Mannich, Michael, and aldol additions, cross-coupling reactions, and biocatalytic approaches.

Marine Polysaccharides in Pharmaceutical Applications: An Overview

PubMed Central

Laurienzo, Paola

2010-01-01

The enormous variety of polysaccharides that can be extracted from marine plants and animal organisms or produced by marine bacteria means that the field of marine polysaccharides is constantly evolving. Recent advances in biological techniques allow high levels of polysaccharides of interest to be produced in vitro. Biotechnology is a powerful tool to obtain polysaccharides from a variety of micro-organisms, by controlling the growth conditions in a bioreactor while tailoring the production of biologically active compounds. Following an overview of the current knowledge on marine polysaccharides, with special attention to potential pharmaceutical applications and to more recent progress on the discovering of new polysaccharides with biological appealing characteristics, this review will focus on possible strategies for chemical or physical modification aimed to tailor the final properties of interest. PMID:20948899

Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

PubMed

Ioset, Jean-Robert; Chang, Shing

2011-09-01

The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

Isolation and structure elucidation of avocado seed (Persea americana) lipid derivatives that inhibit Clostridium sporogenes endospore germination.

PubMed

Rodríguez-Sánchez, Dariana Graciela; Pacheco, Adriana; García-Cruz, María Isabel; Gutiérrez-Uribe, Janet Alejandra; Benavides-Lozano, Jorge Alejandro; Hernández-Brenes, Carmen

2013-07-31

Avocado fruit extracts are known to exhibit antimicrobial properties. However, the effects on bacterial endospores and the identity of antimicrobial compounds have not been fully elucidated. In this study, avocado seed extracts were tested against Clostridium sporogenes vegetative cells and active endospores. Bioassay-guided purification of a crude extract based on inhibitory properties linked antimicrobial action to six lipid derivatives from the family of acetogenin compounds. Two new structures and four compounds known to exist in nature were identified as responsible for the activity. Structurally, most potent molecules shared features of an acetyl moiety and a trans-enone group. All extracts produced inhibition zones on vegetative cells and active endospores. Minimum inhibitory concentrations (MIC) of isolated molecules ranged from 7.8 to 15.6 μg/mL, and bactericidal effects were observed for an enriched fraction at 19.5 μg/mL. Identified molecules showed potential as natural alternatives to additives and antibiotics used by the food and pharmaceutical industries to inhibit Gram-positive spore-forming bacteria.

Exploration of avocado by-products as natural sources of bioactive compounds.

PubMed

Tremocoldi, Maria Augusta; Rosalen, Pedro Luiz; Franchin, Marcelo; Massarioli, Adna Prado; Denny, Carina; Daiuto, Érica Regina; Paschoal, Jonas Augusto Rizzato; Melo, Priscilla Siqueira; Alencar, Severino Matias de

2018-01-01

This study aimed to evaluate the antioxidant, anti-inflammatory, and cytotoxic properties and phenolic composition of peel and seed of avocado varieties Hass and Fuerte using green solvents. Ethanol soluble compounds were identified in peel and seed of both varieties using HPLC-MS/MS and quantified using HPLC-DAD. Agro-industrial by-products of both varieties exhibited high radical scavenging activity against synthetic free radicals (DPPH and ABTS) and reactive oxygen species (peroxyl, superoxide, and hypochlorous acid) and high ability to reduce Fe3+ to Fe2+. The main compounds with significant contribution to the antioxidant activity determined by online HPLC-ABTS●+ analyses were procyanidin B2 and epicatechin in the peel and trans-5-O-caffeoyl-D-quinic acid, procyanidin B1, catechin, and epicatechin in the seed. Peel of Fuerte significantly suppressed TNF-α and nitric oxide (NO) release (459.3 pg/mL and 8.5 μM, respectively), possibly because of the high phenolic content and antioxidant activity detected. Avocado agro-industrial by-products can be used for food and pharmaceutical purposes due to their antioxidant and anti-inflammatory properties.

Exploration of avocado by-products as natural sources of bioactive compounds

PubMed Central

Tremocoldi, Maria Augusta; Rosalen, Pedro Luiz; Franchin, Marcelo; Massarioli, Adna Prado; Denny, Carina; Daiuto, Érica Regina; Paschoal, Jonas Augusto Rizzato; Melo, Priscilla Siqueira

2018-01-01

This study aimed to evaluate the antioxidant, anti-inflammatory, and cytotoxic properties and phenolic composition of peel and seed of avocado varieties Hass and Fuerte using green solvents. Ethanol soluble compounds were identified in peel and seed of both varieties using HPLC-MS/MS and quantified using HPLC-DAD. Agro-industrial by-products of both varieties exhibited high radical scavenging activity against synthetic free radicals (DPPH and ABTS) and reactive oxygen species (peroxyl, superoxide, and hypochlorous acid) and high ability to reduce Fe3+ to Fe2+. The main compounds with significant contribution to the antioxidant activity determined by online HPLC-ABTS●+ analyses were procyanidin B2 and epicatechin in the peel and trans-5-O-caffeoyl-D-quinic acid, procyanidin B1, catechin, and epicatechin in the seed. Peel of Fuerte significantly suppressed TNF-α and nitric oxide (NO) release (459.3 pg/mL and 8.5 μM, respectively), possibly because of the high phenolic content and antioxidant activity detected. Avocado agro-industrial by-products can be used for food and pharmaceutical purposes due to their antioxidant and anti-inflammatory properties. PMID:29444125

Novel biphenyl ester derivatives as tyrosinase inhibitors: Synthesis, crystallographic, spectral analysis and molecular docking studies.

PubMed

Kwong, Huey Chong; Chidan Kumar, C S; Mah, Siau Hui; Chia, Tze Shyang; Quah, Ching Kheng; Loh, Zi Han; Chandraju, Siddegowda; Lim, Gin Keat

2017-01-01

Biphenyl-based compounds are clinically important for the treatments of hypertension and inflammatory, while many more are under development for pharmaceutical uses. In the present study, a series of 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl benzoates, 2(a-q), and 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl pyridinecarboxylate, 2(r-s) were synthesized by reacting 1-([1,1'-biphenyl]-4-yl)-2-bromoethan-1-one with various carboxylic acids using potassium carbonate in dimethylformamide at ambient temperature. Single-crystal X-ray diffraction studies revealed a more closely packed crystal structure can be produced by introduction of biphenyl moiety. Five of the compounds among the reported series exhibited significant anti-tyrosinase activities, in which 2p, 2r and 2s displayed good inhibitions which are comparable to standard inhibitor kojic acid at concentrations of 100 and 250 μg/mL. The inhibitory effects of these active compounds were further confirmed by computational molecular docking studies and the results revealed the primary binding site is active-site entrance instead of inner copper binding site which acted as the secondary binding site.

Comparative studies on extracts from Hericium erinaceus by different polarity reagents to gain higher antioxidant activities.

PubMed

Jiang, Shengjuan; Wang, Yuliang; Zhang, Xiaolong

2016-07-01

Hericium erinaceus (H. erinaceus) is a source of exogenous antioxidants that has been traditionally used in China for the prevention and treatment of oxidative stress-associated disease. In the present study, the bioactive compounds of H. erinaceus were extracted with the following eight representative reagents: n-Hexane, xylene, chloroform, anhydrous ether, ethyl acetate, acetone, anhydrous ethanol and distilled water. The in vitro antioxidant activities were also evaluated. All of the extracted compounds exhibited reducing power and scavenging activity against 1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion free radicals. In addition, the antioxidant capacities varied with the used chemical reagents and exhibited dose-dependent effects. Extracts from anhydrous ethanol, chloroform and acetone were capable of inhibiting lipid peroxidation. The anhydrous ethanol extracts were observed to have significant levels of antioxidant compounds since they had a strong reducing power, high scavenging rates against DPPH and superoxide anion-free radicals (>90%), and high inhibition rates on lipid peroxidation (>60%). The present study will provide reference data for the antioxidant applications of H. erinaceus in pharmaceutical use and disease prevention.

Comparative studies on extracts from Hericium erinaceus by different polarity reagents to gain higher antioxidant activities

PubMed Central

JIANG, SHENGJUAN; WANG, YULIANG; ZHANG, XIAOLONG

2016-01-01

Hericium erinaceus (H. erinaceus) is a source of exogenous antioxidants that has been traditionally used in China for the prevention and treatment of oxidative stress-associated disease. In the present study, the bioactive compounds of H. erinaceus were extracted with the following eight representative reagents: n-Hexane, xylene, chloroform, anhydrous ether, ethyl acetate, acetone, anhydrous ethanol and distilled water. The in vitro antioxidant activities were also evaluated. All of the extracted compounds exhibited reducing power and scavenging activity against 1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion free radicals. In addition, the antioxidant capacities varied with the used chemical reagents and exhibited dose-dependent effects. Extracts from anhydrous ethanol, chloroform and acetone were capable of inhibiting lipid peroxidation. The anhydrous ethanol extracts were observed to have significant levels of antioxidant compounds since they had a strong reducing power, high scavenging rates against DPPH and superoxide anion-free radicals (>90%), and high inhibition rates on lipid peroxidation (>60%). The present study will provide reference data for the antioxidant applications of H. erinaceus in pharmaceutical use and disease prevention. PMID:27347087

Environmental risk analysis and prioritization of pharmaceuticals in a developing world context.

PubMed

Mansour, Fatima; Al-Hindi, Mahmoud; Saad, Walid; Salam, Darine

2016-07-01

The impact of residual pharmaceuticals on the aquatic environment has gained widespread attention over the past years. Various studies have established the occurrence of pharmaceutical compounds in different water bodies throughout the world. In view of the absence of occurrence data in a number of developing world countries, and given the limited availability of analytical resources in these countries, it is prudent to devise methodologies to prioritize pharmaceuticals for environmental monitoring purposes that are site specific. In this work, several prioritization approaches are used to rank the 88 most commonly consumed pharmaceuticals in Lebanon. A simultaneous multi-criteria decision analysis method utilizing the exposure, persistence, bioaccumulation, and toxicity (EPBT) approach is applied to a smaller subset of the original list (69 pharmaceuticals). Several base cases are investigated and sensitivity analysis is applied to one of these base case runs. The similarities and differences in the overall ranking of individual, and classes of, pharmaceuticals for the base cases and the sensitivity runs are elucidated. An environmental risk assessment (ERA), where predicted environmental concentrations (PEC) and risk quotients (RQ) are determined at different dilution factors, is performed as an alternative method of prioritization for a total of 84 pharmaceuticals. The ERA results indicate that metformin and amoxicillin have the highest PECs while 17β-estradiol, naftidrofuryl and dimenhydrinate have the highest RQs. The two approaches, EPBT prioritization and ERA, are compared and a priority list consisting of 26 pharmaceuticals of various classes is developed. Nervous system and alimentary tract and metabolism pharmaceuticals (9/26 and 5/26 respectively) constitute more than half of the numbers on the priority list with the balance consisting of anti-infective (4/26), musculo-skeletal (3/26), genito-urinary (2/26), respiratory (2/26) and cardiovascular (1/26) pharmaceuticals. This list will serve as a basis for the selection of candidate compounds to focus on for future monitoring campaigns. Copyright © 2016 Elsevier B.V. All rights reserved.

Perfluorinated Compounds In The Ohio River Basin

EPA Science Inventory

Contaminants of emerging concern (CECs) in waterways include pharmaceuticals and personal care products (PPCPs), alkylphenols, endocrine disrupting chemicals (EDCs) and perfluorinated alkyl compounds (PFCs). Their distributions and persistence in the aquatic environment remain p...

Bioidentical Hormones and Menopause

MedlinePlus

... made products. These are made in a compounding pharmacy (a pharmacy that mixes medications according to a doctor’s instructions). ... that bioidentical hormones, whether prepared by a compounding pharmacy or pharmaceutical company, are safer to use than ...

Determination of phenolic endocrine disrupting chemicals and acidic pharmaceuticals in surface water of the Pearl Rivers in South China by gas chromatography-negative chemical ionization-mass spectrometry.

PubMed

Zhao, Jian-Liang; Ying, Guang-Guo; Wang, Li; Yang, Ji-Feng; Yang, Xiao-Bing; Yang, Li-Hua; Li, Xu

2009-01-01

An analytical method for phenolic endocrine disrupting chemicals and acidic pharmaceuticals in river water was developed using gas chromatography mass spectrometry (GC-MS) coupled with negative chemical ionization (NCI) technique, and used for the determination of these compounds in the Pearl Rivers (Liuxi, Zhujiang and Shijing Rivers). Derivatization using pentafluorobenzoyl chloride (PFBOCl) and pentafluorobenzyl bromide (PFBBr) before GC-MS analysis were applied and optimized for phenolic compounds and acidic compounds, respectively. The target compounds were analyzed for river waters from the upstream to downstream of the Pearl Rivers. Phenolic compounds 4-tert-octylphenol (4-t-OP), 4-nonylphenol (4-NP), bisphenol-A (BPA), estrone (E1), estradiol (E2) and triclosan (TCS) were detected at trace or low levels in the water samples from Liuxi River and Zhujiang River. Diethylstilbestrol (DES) was not detected in the Pearl Rivers. The highest concentrations of the phenolic compounds were found in Shijing River, and they were 3150 ng/L for 4-t-OP, 11,300 ng/L for 4-NP, 1040 ng/L for BPA, 79 ng/L for E1, 7.7 ng/L for E2 and 355 ng/L for TCS, respectively. Only a few acidic pharmaceuticals were detected at low concentrations in water from Liuxi River and Zhujiang River, but the highest concentrations for the acidic pharmaceuticals were also found in Shijing River. The highest concentrations detected for clofibric acid, ibuprofen, gemfibrozil, naproxen, mefenamic acid and diclofenac were 17 ng/L, 685 ng/L, 19.8 ng/L, 125 ng/L, 24.6 ng/l and 150 ng/L, respectively. The results suggest Liuxi and Zhujiang Rivers are only slightly contaminated and can be used as drinking water sources, but Shijing River is heavily polluted by the wastewater from nearby towns.

Removal of pharmaceuticals from wastewater by biological processes, hydrodynamic cavitation and UV treatment.

PubMed

Zupanc, Mojca; Kosjek, Tina; Petkovšek, Martin; Dular, Matevž; Kompare, Boris; Širok, Brane; Blažeka, Željko; Heath, Ester

2013-07-01

To augment the removal of pharmaceuticals different conventional and alternative wastewater treatment processes and their combinations were investigated. We tested the efficiency of (1) two distinct laboratory scale biological processes: suspended activated sludge and attached-growth biomass, (2) a combined hydrodynamic cavitation-hydrogen peroxide process and (3) UV treatment. Five pharmaceuticals were chosen including ibuprofen, naproxen, ketoprofen, carbamazepine and diclofenac, and an active metabolite of the lipid regulating agent clofibric acid. Biological treatment efficiency was evaluated using lab-scale suspended activated sludge and moving bed biofilm flow-through reactors, which were operated under identical conditions in respect to hydraulic retention time, working volume, concentration of added pharmaceuticals and synthetic wastewater composition. The suspended activated sludge process showed poor and inconsistent removal of clofibric acid, carbamazepine and diclofenac, while ibuprofen, naproxen and ketoprofen yielded over 74% removal. Moving bed biofilm reactors were filled with two different types of carriers i.e. Kaldnes K1 and Mutag BioChip™ and resulted in higher removal efficiencies for ibuprofen and diclofenac. Augmentation and consistency in the removal of diclofenac were observed in reactors using Mutag BioChip™ carriers (85%±10%) compared to reactors using Kaldnes carriers and suspended activated sludge (74%±22% and 48%±19%, respectively). To enhance the removal of pharmaceuticals hydrodynamic cavitation with hydrogen peroxide process was evaluated and optimal conditions for removal were established regarding the duration of cavitation, amount of added hydrogen peroxide and initial pressure, all of which influence the efficiency of the process. Optimal parameters resulted in removal efficiencies between 3-70%. Coupling the attached-growth biomass biological treatment, hydrodynamic cavitation/hydrogen peroxide process and UV treatment resulted in removal efficiencies of >90% for clofibric acid and >98% for carbamazepine and diclofenac, while the remaining compounds were reduced to levels below the LOD. For ibuprofen, naproxen, ketoprofen and diclofenac the highest contribution to overall removal was attributed to biological treatment, for clofibric acid UV treatment was the most efficient, while for carbamazepine hydrodynamic cavitation/hydrogen peroxide process and UV treatment were equally efficient. Copyright © 2012 Elsevier B.V. All rights reserved.

FATE OF PHARMACEUTICALS: EFFECTS OF CHLORINATION AND ENVIRONMENTAL PERSISTENCE

EPA Science Inventory

The presence of pharmaceuticals in environmental waters has become an area of concern around the world. To maximize the impact of occurrence studies, pre-screening can help determine which compounds are likely to survive waste water treatment, as well as what by-products are for...

DETERMINATION OF THE POTENTIAL FOR ANAEROBIC DEGRADATION OF UNUSED PHARMACEUTICALS IN MUNICIPAL SOLID WASTE LANDFILLS

EPA Science Inventory

For many years the recommended method of disposal for unused household medications was the sewage system. However, research studies have emerged showing that many pharmaceuticals and endocrine disrupting compounds are not fully removed by wastewater treatment systems and enter t...

Analysis of pharmaceutical and other organic wastewater compounds in filtered and unfiltered water samples by gas chromatography/mass spectrometry

USGS Publications Warehouse

Zaugg, Steven D.; Phillips, Patrick J.; Smith, Steven G.

2014-01-01

Research on the effects of exposure of stream biota to complex mixtures of pharmaceuticals and other organic compounds associated with wastewater requires the development of additional analytical capabilities for these compounds in water samples. Two gas chromatography/mass spectrometry (GC/MS) analytical methods used at the U.S. Geological Survey National Water Quality Laboratory (NWQL) to analyze organic compounds associated with wastewater were adapted to include additional pharmaceutical and other organic compounds beginning in 2009. This report includes a description of method performance for 42 additional compounds for the filtered-water method (hereafter referred to as the filtered method) and 46 additional compounds for the unfiltered-water method (hereafter referred to as the unfiltered method). The method performance for the filtered method described in this report has been published for seven of these compounds; however, the addition of several other compounds to the filtered method and the addition of the compounds to the unfiltered method resulted in the need to document method performance for both of the modified methods. Most of these added compounds are pharmaceuticals or pharmaceutical degradates, although two nonpharmaceutical compounds are included in each method. The main pharmaceutical compound classes added to the two modified methods include muscle relaxants, opiates, analgesics, and sedatives. These types of compounds were added to the original filtered and unfiltered methods largely in response to the tentative identification of a wide range of pharmaceutical and other organic compounds in samples collected from wastewater-treatment plants. Filtered water samples are extracted by vacuum through disposable solid-phase cartridges that contain modified polystyrene-divinylbenzene resin. Unfiltered samples are extracted by using continuous liquid-liquid extraction with dichloromethane. The compounds of interest for filtered and unfiltered sample types were determined by use of the capillary-column gas chromatography/mass spectrometry. The performance of each method was assessed by using data on recoveries of compounds in fortified surface-water, wastewater, and reagent-water samples. These experiments (referred to as spike experiments) consist of fortifying (or spiking) samples with known amounts of target analytes. Surface-water-spike experiments were performed by using samples obtained from a stream in Colorado (unfiltered method) and a stream in New York (filtered method). Wastewater spike experiments for both the filtered and unfiltered methods were performed by using a treated wastewater obtained from a single wastewater treatment plant in New York. Surface water and wastewater spike experiments were fortified at both low and high concentrations and termed low- and high-level spikes, respectively. Reagent water spikes were assessed in three ways: (1) set spikes, (2) a low-concentration fortification experiment, and (3) a high-concentration fortification experiment. Set spike samples have been determined since 2009, and consist of analysis of fortified reagent water for target compounds included for each group of 10 to18 environmental samples analyzed at the NWQL. The low-concentration and high-concentration reagent spike experiments, by contrast, represent a one-time assessment of method performance. For each spike experiment, mean recoveries ranging from 60 to 130 percent indicate low bias, and relative standard deviations (RSDs) less than ( Of the compounds included in the filtered method, 21 had mean recoveries ranging from 63 to 129 percent for the low-level and high-level surface-water spikes, and had low ()132 percent]. For wastewater spikes, 24 of the compounds included in the filtered method had recoveries ranging from 61 to 130 percent for the low-level and high-level spikes. RSDs were 130 percent) or variable recoveries (RSDs >30 percent) for low-level wastewater spikes, or low recoveries ( Of the compounds included in the unfiltered method, 17 had mean spike recoveries ranging from 74 to 129 percent and RSDs ranging from 5 to 25 percent for low-level and high-level surface water spikes. The remaining compounds had poor mean recoveries (130 percent), or high RSDs (>29 percent) for these spikes. For wastewater, 14 of the compounds included in the unfiltered method had mean recoveries ranging from 62 to 127 percent and RSDs 130 percent), or low mean recoveries (33 percent) for the low-level wastewater spikes. Of the compounds found in wastewater, 24 had mean set spike recoveries ranging from 64 to 104 percent and RSDs Separate method detection limits (MDLs) were computed for surface water and wastewater for both the filtered and unfiltered methods. Filtered method MDLs ranged from 0.007 to 0.14 microgram per liter (μg/L) for the surface water matrix and from 0.004 to 0.62 μg/L for the wastewater matrix. Unfiltered method MDLs ranged from 0.014 to 0.33 μg/L for the surface water matrix and from 0.008 to 0.36 μg/L for the wastewater matrix.

Target specific compound identification using a support vector machine.

PubMed

Plewczynski, Dariusz; von Grotthuss, Marcin; Spieser, Stephane A H; Rychlewski, Leszek; Wyrwicz, Lucjan S; Ginalski, Krzysztof; Koch, Uwe

2007-03-01

In many cases at the beginning of an HTS-campaign, some information about active molecules is already available. Often known active compounds (such as substrate analogues, natural products, inhibitors of a related protein or ligands published by a pharmaceutical company) are identified in low-throughput validation studies of the biochemical target. In this study we evaluate the effectiveness of a support vector machine applied for those compounds and used to classify a collection with unknown activity. This approach was aimed at reducing the number of compounds to be tested against the given target. Our method predicts the biological activity of chemical compounds based on only the atom pairs (AP) two dimensional topological descriptors. The supervised support vector machine (SVM) method herein is trained on compounds from the MDL drug data report (MDDR) known to be active for specific protein target. For detailed analysis, five different biological targets were selected including cyclooxygenase-2, dihydrofolate reductase, thrombin, HIV-reverse transcriptase and antagonists of the estrogen receptor. The accuracy of compound identification was estimated using the recall and precision values. The sensitivities for all protein targets exceeded 80% and the classification performance reached 100% for selected targets. In another application of the method, we addressed the absence of an initial set of active compounds for a selected protein target at the beginning of an HTS-campaign. In such a case, virtual high-throughput screening (vHTS) is usually applied by using a flexible docking procedure. However, the vHTS experiment typically contains a large percentage of false positives that should be verified by costly and time-consuming experimental follow-up assays. The subsequent use of our machine learning method was found to improve the speed (since the docking procedure was not required for all compounds from the database) and also the accuracy of the HTS hit lists (the enrichment factor).