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Sample records for drug residues

  1. Safety assessment of drug residues

    SciTech Connect

    Jackson, B.A.

    1980-05-15

    The safety assessment of drug residues is part of the process for defining the conditions for the safe use of drugs in food-producing animals. The information needed to assess the safety of drug residues is provided by chemical and toxicity tests. Toxicity tests are conducted to identify the type of effect produced and to determine the exposure concentrations that would be expected not to produce the effect. These tests include acute, subacute, and chronic toxicity tests, as well as reproduction studies and other special tests. The results are used to find an acceptable daily intake for drug residues that can be used to set a tolerance.

  2. Distribution of veterinary drug residues among muscles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The U.S. Food and Drug Administration sets tolerances for veterinary drug residues in muscle, but does not specify which muscle should be sampled for analysis. The goal of this research was to determine if antibiotic residue levels are dependent on muscle type. In this study, penicillin G (Pen G) d...

  3. Evaluation of certain veterinary drug residues in food.

    PubMed

    2009-01-01

    This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers general principles regarding the evaluation of veterinary drugs within the terms of reference of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), including a hypothesis-driven decision tree approach for the safety evaluation of residues of veterinary drugs; comments on the Committee for Veterinary Products for Medicinal Use reflection paper on the new approach developed by JECFA for exposure and maximum residue limit (MRL) assessment of residues; residues of veterinary drugs in honey and possible approaches to derive MRLs for this commodity; comments on a paper entitled "Risk-assessment policies: Differences among jurisdictions"; and the use of no-observed-effect level (NOEL) and no-observed-adverse-effect level (NOAEL) in JECFA assessments. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: three antimicrobial agents (avilamycin, tilmicosin, tylosin), one anthelminthic (triclabendazole), one production aid (melengestrol acetate), two antimicrobial agents and production aids (monensin and narasin), a glucocarticosteroid (dexamethasone) and an antimicrobial agent and contaminant (malachite green). Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes (ADIs) and proposed MRLs. PMID:20112498

  4. Evaluation of certain veterinary drug residues in food.

    PubMed

    2001-01-01

    This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers the interpretation of data on inhibition of cholinesterase activity and recommendations arising from an informal meeting on harmonization with the Joint FAO/WHO Meeting on Pesticide Residues. A summary follows of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: one anthelminthic agent (ivermectin); four antimicrobial agents (flumequine, lincomycin, oxytetracycline and tilmicosin); six insecticides (cyhalothrin, cypermethrin, alpha-cypermethrin, dicyclanil, permethrin and metrifonate (trichlorfon)); and one production aid (melengestrol acetate). Annexed to the report are a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and Maximum Residue Limits and further information required. PMID:11402526

  5. 75 FR 45640 - Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Residual Drug in Transdermal... guidance for industry entitled ``Residual Drug in Transdermal and Related Drug Delivery Systems.'' This... of a draft guidance for industry entitled ``Residual Drug in Transdermal and Related Drug...

  6. Stability during cooking of anthelmintic veterinary drug residues in beef.

    PubMed

    Cooper, K M; Whelan, M; Danaher, M; Kennedy, D G

    2011-02-01

    Anthelmintic drugs are widely used for treatment of parasitic worms in livestock, but little is known about the stability of their residues in food under conventional cooking conditions. As part of the European Commission-funded research project ProSafeBeef, cattle were medicated with commercially available anthelmintic preparations, comprising 11 active ingredients (corresponding to 21 marker residues). Incurred meat and liver were cooked by roasting (40 min at 190°C) or shallow frying (muscle 8-12 min, liver 14-19 min) in a domestic kitchen. Raw and cooked tissues and expressed juices were analysed using a novel multi-residue dispersive solid-phase extraction method (QuEChERS) coupled with ultra-performance liquid chromatography-tandem mass spectrometry. After correction for sample weight changes during cooking, no major losses were observed for residues of oxyclozanide, clorsulon, closantel, ivermectin, albendazole, mebendazole or fenbendazole. However, significant losses were observed for nitroxynil (78% in fried muscle, 96% in roast muscle), levamisole (11% in fried muscle, 42% in fried liver), rafoxanide (17% in fried muscle, 18% in roast muscle) and triclabendazole (23% in fried liver, 47% in roast muscle). Migration of residues from muscle into expressed cooking juices varied between drugs, constituting 0% to 17% (levamisole) of total residues remaining after cooking. With the exception of nitroxynil, residues of anthelmintic drugs were generally resistant to degradation during roasting and shallow frying. Conventional cooking cannot, therefore, be considered a safeguard against ingestion of residues of anthelmintic veterinary drugs in beef. PMID:21240825

  7. Evaluation of certain veterinary drug residues in food.

    PubMed

    2002-01-01

    This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers risk assessment principles and presents the views of the Committee on the FAO/WHO Project to update principles and methods for the risk assessment of chemicals in food. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: three anthelminthic agents (doramectin, ivermectin and tiabendazole), seven antimicrobial agents (cefuroxime, dihydrostreptomycin and streptomycin, lincomycin, neomycin, oxytetracycline and thiamphenicol), four insecticides (cyhalothrin, cypermethrin and alpha-cypermethrin, and phoxim) and one production aid (melengestrol acetate). Annexed to the report is a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and Maximum Residue Limits and further information required. PMID:12592988

  8. Small molecule microarrays for drug residue detection in foodstuffs.

    PubMed

    Peng, Zuo; Bang-Ce, Ye

    2006-09-20

    Microarrays have been used as tools for analyzing biological compositions at different levels. In this study, we proposed a small molecule microarray (SMM) method for detection of three veterinary drug residues, chloramphenicol, clenbuterol, and tylosin, in foodstuffs simultaneously and quantitatively. The small drug molecules were immobilized on the surface of the modified glass slides. Then the mixture of drug corresponding antibodies and standards or samples was added to the reaction area. After incubation, the antigen-antibody binding was detected using cy5 labeled secondary antibody. The calibration curves of the residues were drawn, and they indicated the lowest detection limit the linearity range. The detectable concentrations of the three residues are lower than the maximum residue levels (MRLs). No cross reactivity was found among the three residues. The coefficient of variation of the spot intensities was below 5% in a subarray, and below 15% among subarrays. The spike sample test and the comparison of detection results by SMMs and ELISA demonstrated the accuracy of the proposed SMMs method. PMID:16968051

  9. Residues of antibacterial drugs in honey from the Italian market.

    PubMed

    Baggio, A; Gallina, A; Benetti, C; Mutinelli, F

    2009-01-01

    Antibacterial drugs are used worldwide for the control of American and, less often, European foulbrood. Their administration is mostly uncontrolled and applied without approved protocols and instructions for use as well as precautionary recommendations. Consequently, this practice is responsible for the contamination of beehive products and contributes to the problem of food safety. According to this situation, 4672 analyses were carried out on 5303 honeys collected from 2001 to 2007. These samples were investigated for antibacterial residues of tetracyclines, sulphonamides, streptomycin, chloramphenicol and tylosin. Honeys were classified according to their origin: imported honey and honey from the Italian market. In the last group (only for samples collected from 2001 to 2004), another type of honey was distinguished: that of local honey. A total of 6.3% of all samples were positive for the antibacterial drugs analysed; in particular, 6.8% of imported honeys and 6.1% of honeys on the Italian market. Only 1.7% of local honey had antibacterial residues. These results are indicative of a rather frequent presence of antibacterial drug residues in both Italian and imported honeys. Furthermore, the data showed that among the active substances analysed, sulphonamides are the most used antibacterial substance followed by tetracyclines, streptomycin, tylosin, and chloramphenicol. Finally, a continuous monitoring programme is needed, accompanied by an education programme to beekeepers on proper hive management. PMID:24784967

  10. Kinetic modelling and residue depletion of drugs in eggs.

    PubMed

    Hekman, P; Schefferlie, G J

    2011-06-01

    1. A physiologically-based pharmacokinetic model was developed for the purpose of describing the relationship between plasma concentration of drugs and their deposition into eggs. 2. By incorporating the physiology of egg formation into the model, the transfer of drugs into the egg albumen and yolk could be described using rate constants. 3. The model was used to describe concentrations in albumen and yolk of sulphanilamide, sulphaquinoxaline and pyrimethamine as a function of time using datasets from the literature. 4. The model could be used as a tool to obtain an insight into those properties of a drug which are responsible for the amount of residue in eggs, and could help in the design of critical studies for determining withdrawal periods for eggs. PMID:21732884

  11. Estimating provisional acceptable residues for extralabel drug use in livestock.

    PubMed

    Baynes, R E; Martín-Jiménez, T; Craigmill, A L; Riviere, J E

    1999-06-01

    In 1996, the United States Congress passed legislation (Animal Medicinal Drug Use Clarification Act, AMDUCA), which allows some veterinary or human drugs to be used off label in food-producing animals. In order to implement this Act and protect the U.S. consumer, tolerances or safe concentrations are required before a withdrawal time can be estimated for extralabel drug use. Use of foreign MRLs to satisfy these data needs may not be applicable because of differences in safety standards between the U.S. and other countries. This paper presents strategies that can be used to derive equivalent safe concentrations, referred to as provisional acceptable residues (PARs), that may then be used to estimate drug withdrawal times. Health-based methods are proposed for calculating a PAR for a tissue. Procedure A partitions 50% of the acceptable daily intake (ADI) to edible tissues and reserves the remainder for milk. Procedure B equally partitions the ADI into all edible tissues. Procedure C partitions 50% of the ADI to milk and equally partitions the remaining 50% ADI into edible tissues. Simulations were performed for florfenicol, tetracycline, dexamethasone, azaperone, ivermectin, eprinomectin, and doramectin. In general, these simulations resulted in derivation of conservative PARs, which did not result in daily intakes of residues greater than the health-based ADI. These simulations demonstrated that provided the safe concentrations or equivalent PARs are based on rigorous toxicology safety data (e.g., NOELs, ADIs), the safety of food animal products will not be compromised. It is proposed that these PARs can be used for estimating withdrawal times after extralabel drug use or inadvertent exposure to an environmental contaminant where no approved withdrawal time exists. Finally, implementing similar transparent methods could have a positive impact on international harmonization and trade. PMID:10388614

  12. Antibiotic residues and drug resistance in human intestinal flora.

    PubMed Central

    Corpet, D E

    1987-01-01

    The effect of residual levels of ampicillin on the drug resistance of fecal flora was studied in human volunteers given 1.5 mg of ampicillin orally per day for 21 days. This treatment failed to have any significant reproducible effect on the number of resistant Escherichia coli in their feces. The effect of continuous administration of small doses of ampicillin, chlortetracycline, or streptomycin in the drinking water was studied in gnotobiotic mice inoculated with a human fecal flora. In this animal model, which is free of many interfering factors, an increase in the fecal concentration of resistant E. coli was observed when the mice were given 0.5 microgram of ampicillin or chlortetracycline per ml of water. This model is therefore a sensitive system for testing the effect of antimicrobial drugs on the resistance characteristics of the intestinal flora. PMID:3300533

  13. 21 CFR 556.1 - General considerations; tolerances for residues of new animal drugs in food.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... new animal drugs in food. 556.1 Section 556.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD General Provisions § 556.1 General considerations; tolerances...

  14. Protein microarray: sensitive and effective immunodetection for drug residues

    PubMed Central

    2010-01-01

    Background Veterinary drugs such as clenbuterol (CL) and sulfamethazine (SM2) are low molecular weight (<1000 Da) compounds, or haptens, that are difficult to develop immunoassays due to their low immunogenicity. In this study, we conjugated the drugs to ovalbumin to increase their immunogenicity for antiserum production in rabbits and developed a protein microarray immunoassay for detection of clenbuterol and sulfamethazine. The sensitivity of this approach was then compared to traditional ELISA technique. Results The artificial antigens were spotted on microarray slides. Standard concentrations of the compounds were added to compete with the spotted antigens for binding to the antisera to determine the IC50. Our microarray assay showed the IC50 were 39.6 ng/ml for CL and 48.8 ng/ml for SM2, while the traditional competitive indirect-ELISA (ci-ELISA) showed the IC50 were 190.7 ng/ml for CL and 156.7 ng/ml for SM2. We further validated the two methods with CL fortified chicken muscle tissues, and the protein microarray assay showed 90% recovery while the ci-ELISA had 76% recovery rate. When tested with CL-fed chicken muscle tissues, the protein microarray assay had higher sensitivity (0.9 ng/g) than the ci-ELISA (0.1 ng/g) for detection of CL residues. Conclusions The protein microarrays showed 4.5 and 3.5 times lower IC50 than the ci-ELISA detection for CL and SM2, respectively, suggesting that immunodetection of small molecules with protein microarray is a better approach than the traditional ELISA technique. PMID:20158905

  15. 75 FR 75482 - Draft Guidance for Industry on Residual Solvents in Animal Drug Products; Questions and Answers...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-03

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Residual Solvents in Animal... guidance for industry 211 entitled ``Residual Solvents in Animal Drug Products; Questions and Answers... availability of a draft guidance for industry 211 entitled ``Residual Solvents in Animal ] Drug...

  16. 77 FR 3653 - Import Tolerances for Residues of Unapproved New Animal Drugs in Food

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... the Federal Register of August 10, 2001 (66 FR 42167), the Agency published an advance notice of... Effects Abroad of Major Federal Actions,'' of January 4, 1979 (44 FR 1957, January 9, 1979); and 21 CFR 25... Tolerances for Residues of Unapproved New Animal Drugs in Food AGENCY: Food and Drug Administration,...

  17. 21 CFR 530.24 - Procedure for announcing analytical methods for drug residue quantification.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Procedure for announcing analytical methods for...-Producing Animals § 530.24 Procedure for announcing analytical methods for drug residue quantification. (a) FDA may issue an order announcing a specific analytical method or methods for the quantification...

  18. Determination of anthelmintic drug residues in milk using UPLC-MS/MS with rapid polarity switching

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A new UPLC-MS/MS (ultra-performance liquid chromatography coupled to tandem mass spectrometry) method was developed and validated to detect 38 anthelmintic drug residues, consisting of benzimidazoles, avermectins and flukicides. A modified QuEChERS-type extraction method was developed with an added...

  19. Development of Analytical Method and Monitoring of Veterinary Drug Residues in Korean Animal Products

    PubMed Central

    Song, Jae-Sang; Park, Su-Jeong; Choi, Jung-Yun; Kim, Jin-Sook; Kang, Myung-Hee; Choi, Bo-Kyung

    2016-01-01

    This study was conducted to determine the residual amount of veterinary drugs such as meloxicam, flunixin, and tulathromycin in animal products (beef, pork, horsemeat, and milk). Veterinary drugs have been widely used in the rearing of livestock to prevent and treat diseases. A total of 152 samples were purchased from markets located in major Korean cities (Seoul, Busan, Incheon, Daegu, Daejeon, Gwangju, Ulsan and Jeju), including Jeju. Veterinary drugs were analyzed by liquid chromatography-tandem mass spectrometry according to the Korean Food Standards Code. The resulting data, which are located within 70-120% of recovery range and less than 20% of relative standard deviations, are in compliance with the criteria of CODEX. A total of five veterinary drugs were detected in 152 samples, giving a detection rate of approximately 3.3%; and no food source violated the guideline values. Our result indicated that most of the veterinary drug residues in animal products were below the maximum residue limits specified in Korea. PMID:27433102

  20. Development of Analytical Method and Monitoring of Veterinary Drug Residues in Korean Animal Products.

    PubMed

    Song, Jae-Sang; Park, Su-Jeong; Choi, Jung-Yun; Kim, Jin-Sook; Kang, Myung-Hee; Choi, Bo-Kyung; Hur, Sun Jin

    2016-01-01

    This study was conducted to determine the residual amount of veterinary drugs such as meloxicam, flunixin, and tulathromycin in animal products (beef, pork, horsemeat, and milk). Veterinary drugs have been widely used in the rearing of livestock to prevent and treat diseases. A total of 152 samples were purchased from markets located in major Korean cities (Seoul, Busan, Incheon, Daegu, Daejeon, Gwangju, Ulsan and Jeju), including Jeju. Veterinary drugs were analyzed by liquid chromatography-tandem mass spectrometry according to the Korean Food Standards Code. The resulting data, which are located within 70-120% of recovery range and less than 20% of relative standard deviations, are in compliance with the criteria of CODEX. A total of five veterinary drugs were detected in 152 samples, giving a detection rate of approximately 3.3%; and no food source violated the guideline values. Our result indicated that most of the veterinary drug residues in animal products were below the maximum residue limits specified in Korea. PMID:27433102

  1. The effect of cooking on veterinary drug residues in food: nicarbazin (dinitrocarbanilide component).

    PubMed

    Tarbin, J A; Bygrave, J; Bigwood, T; Hardy, D; Rose, M; Sharman, M

    2005-11-01

    The change of concentration of residues of the marker compound for the anti-coccidial drug nicarbazin, N,N'-bis(4-nitrophenyl)urea (dinitrocarbanilide, DNC), was investigated in model oil and aqueous solutions and in chicken muscle and egg. In model aqueous solutions, DNC decreased rapidly in concentration upon heating followed by a much more gradual decomposition. The curves produced when this information was plotted were not typical of exponential decay. In model cooking oil solutions, DNC generally showed a slower decrease in concentration over time when compared with aqueous solutions. DNC residues in egg were stable to microwave cooking and residues in chicken muscle were stable to stewing and microwaving. Other cooking procedures led to a decrease in amount of DNC by 22% to 48% of the total amount of analyte present. Only a small amount (<2%) of residue leached with juices which exuded as the food was cooked. PMID:16332636

  2. Novel in vitro systems for prediction of veterinary drug residues in ovine milk and dairy products.

    PubMed

    González-Lobato, L; Real, R; Herrero, D; de la Fuente, A; Prieto, J G; Marqués, M M; Alvarez, A I; Merino, G

    2014-01-01

    A new in vitro tool was developed for the identification of veterinary substrates of the main drug transporter in the mammary gland. These drugs have a much higher chance of being concentrated into ovine milk and thus should be detectable in dairy products. Complementarily, a cell model for the identification of compounds that can inhibit the secretion of drugs into ovine milk, and thus reduce milk residues, was also generated. The ATP-binding cassette transporter G2 (ABCG2) is responsible for the concentration of its substrates into milk. The need to predict potential drug residues in ruminant milk has prompted the development of in vitro cell models over-expressing ABCG2 for these species to detect veterinary drugs that interact with this transporter. Using these models, several substrates for bovine and caprine ABCG2 have been found, and differences in activity between species have been reported. However, despite being of great toxicological relevance, no suitable in vitro model to predict substrates of ovine ABCG2 was available. New MDCKII and MEF3.8 cell models over-expressing ovine ABCG2 were generated for the identification of substrates and inhibitors of ovine ABCG2. Five widely used veterinary antibiotics (marbofloxacin, orbifloxacin, sarafloxacin, danofloxacin and difloxacin) were discovered as new substrates of ovine ABCG2. These results were confirmed for the bovine transporter and its Y581S variant using previously generated cell models. In addition, the avermectin doramectin was described as a new inhibitor of ruminant ABCG2. This new rapid assay to identify veterinary drugs that can be concentrated into ovine milk will potentially improve detection and monitoring of veterinary drug residues in ovine milk and dairy products. PMID:24679113

  3. 76 FR 51038 - Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... August 3, 2010 (75 FR 45640), FDA announced the availability of the draft version of this guidance. The... prolonged pharmacological effect of the drug. Also, some children have died from inadvertent exposure...

  4. Tools to evaluate pharmacokinetics data for establishing maximum residue limits for approved veterinary drugs: examples from JECFA's work.

    PubMed

    Sanders, P; Henri, J; Laurentie, M

    2016-05-01

    Maximum residue limits (MRLs) for residues of veterinary drugs are the maximum concentrations of residues permitted in or on a food by national or regional legislation. In the process of MRLs recommendations by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), analysis of pharmacokinetic data describing the ADME process (absorption, distribution, metabolism and excretion) is a crucial step and requires the use of different pharmacokinetic tools. The results of animal metabolism studies are the prime determinants of the residue definition in food commodities. Substances labelled with radioactive isotopes are used so that the disposition of the residue can be followed as total residue and main metabolites concentrations. Residue depletion studies with radiolabelled parent drug will lead to the estimate of the time course of the total residue and to determine a marker residue. Depletion studies with an unlabelled drug provide more information on the time course of the marker residue in raw commodities after administration under approved practical conditions of use. By use of this information and after conversion with the total/residue marker ratio, MRLs are derived by comparison of the acceptable daily intake with the daily intakes calculated with different scenarios of dietary exposure. Progress in pharmacokinetic model such as physiologically based pharmacokinetics and population pharmacokinetics will drive the future research in this field to improved veterinary drug development. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27443212

  5. Electrochemical oxidation of drug residues in water by the example of tetracycline, gentamicine and aspirin.

    PubMed

    Weichgrebe, D; Danilova, E; Rosenwinkel, K H; Vedenjapin, A A; Baturova, M

    2004-01-01

    Electro-chemical oxidation as a method to destroy drug residues like aspirin, tetracycline or gentamicine in water was investigated with C-anodes (modified by manganese oxides) and Pt anodes. The mechanism of aspirin and tetracycline oxidation and the influence of the biocide effect was observed using GC-MS and three different microbiological tests. In general, the biological availability increases with progressive oxidation of the antibiotics. PMID:15077972

  6. Residual activity of anticoccidial drugs in chickens after withdrawal of medicated feeds.

    PubMed

    McDougald, L R; Seibert, B P

    1998-01-31

    Seven anticoccidial drugs commonly used in poultry (diclazuri), monensin, salinomycin, halofuginone, nicarbazin, robenidine, amprolium, and lasalocid) were tested for residual activity after withdrawal. In each test, the products were given at the recommended level to cages of 10 broiler chickens. Oral inoculation with coccidia was given after withdrawal of medication. Birds pretreated with 1 ppm of diclazuril and inoculated with Eimeria tenella after drug withdrawal had normal weight gain and very low lesion scores. Residual activity depleted gradually over several days, as shown by higher lesion scores when medication was withdrawn for up to 3 days before inoculation. Similar results were observed when young birds were inoculated with a mixture of E. tenella, E. maxima and E. acervulina, and also when birds were given diclazuril to market weight (6 weeks of age) and inoculated with a mixture of six species of Eiméria (The above species plus E. brunetti, E. mitis, and E. necatrix) after withdrawal of medication for 2 days. In contrast, there was no evidence of residual anticoccidial activity with nicarbazin, halofuginone, lasalocid, amprolium, salinomycin or monensin. Overall, the residual activity was unique to diclazuril. PMID:9561697

  7. Assessment of antimicrobial drug residues in beef in Abuja, the Federal Capital Territory, Nigeria.

    PubMed

    Omeiza, Gabriel K; Ajayi, Itopa E; Ode, Okwoche J

    2012-01-01

    Drugs administered to food-producing animals close to the time of slaughter often result in prohibited antimicrobial residues in the animal tissues at slaughter. Evidence based on the Premi® test confirmed the occurrence of antimicrobial drug residues in 89.3% of kidney and urine samples from cattle slaughtered within Abuja town where the residents rely heavily on beef as a source of protein. The administration of antibiotics close to the time of slaughter by marketers/herd owners and transporters was found to be significantly (p<0.05) higher when compared with butchers and abattoir workers. The practice of administering antibiotics to animals close to the time of slaughter was believed to be profit-motivated. The research suggests that awareness campaigns amongst the stakeholders, the enactment of appropriate laws for the control of antibiotic use and the empowerment of veterinary public health practitioners in food regulatory agencies as some of the strategies which may positively reduce the risk of antimicrobial drug residues in food animals in Nigeria. PMID:23038074

  8. Effective management tools for participants at Codex Committee on Residues of Veterinary Drugs meetings.

    PubMed

    Kay, Jack F

    2016-05-01

    The Codex Committee on Residues of Veterinary Drugs in Food (CCRVDF) fulfils a number of functions revolving around standard setting. The core activities of the CCRVDF include agreeing priorities for assessing veterinary drug residues, recommending maximum residue limits for veterinary drugs in foods of animal origin, considering methods of sampling and analyses, and developing codes of practice. Draft standards are developed and progress through an agreed series of steps common to all Codex Alimentarius Commission Committees. Meetings of the CCRVDF are held at approximately 18-month intervals. To ensure effective progress is made with meetings at this frequency, the CCRVDF makes use of a number of management tools. These include circular letters to interested parties, physical and electronic drafting groups between plenary sessions, meetings of interested parties immediately prior to sessions, as well as break out groups within sessions and detailed discussions within the CCRVDF plenary sessions. A range of these approaches is required to assist advances within the standards setting process and can be applied to other Codex areas and international standard setting more generally. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27443198

  9. [Do pharmaceutical waste and drug residue pose a risk to public health?].

    PubMed

    Haguenoer, Jean-Marie

    2010-01-01

    Recently, awareness has developed of the environmental consequences of drug waste and disposal. These residues are identified as coming from either diffuse sources, the most significant of which is via the discharge of these residues in urine and feces, and thus the sewage system and water contains these drug remnants and their metabolites, or from point sources, sometimes with very high levels of concentration in waste from chemical and pharmaceutical industries, health care settings, but also from intensive livestock farming and aquaculture. Depending on their physical chemistry properties, these substances are more or less naturally biodegradable and easily treated in sewage purification plants. The effectiveness of these treatment processes is highly random and unpredictable, but is overall around 60%, nevertheless with variations of 2-99% according to the molecules. The silt from these treatment plants, sometimes very rich in lipophilic substances is on occasion reused for agricultural application as fertilizer, paving the way for a possible contamination of crops. Furthermore, the use of veterinary drugs in animals can lead to soil contamination either directly or through manure and slurry. The contamination can equally reach and affect surface water, groundwater and sometimes the water intended for human consumption. The National academy of Pharmacy has established some general recommendations on the proper use of drugs, environmental monitoring and surveillance, risk assessment for humans and the environment, prevention and the need for prevention. Several categories of drugs are more worrying: cancer treatments, antibiotics as well as transfers of anti-bio-resistance, and hormonal derivatives which has been previously demonstrated to contribute, along with other molecules, to detrimental effects on endocrines. PMID:20858332

  10. A generic static headspace gas chromatography method for determination of residual solvents in drug substance.

    PubMed

    Cheng, Chang; Liu, Shaorong; Mueller, Bradford J; Yan, Zimeng

    2010-10-01

    In order to increase productivity of drug analysis in the pharmaceutical industry, an efficient and sensitive generic static headspace gas chromatography (HSGC) method was successfully developed and validated for the determination of 44 classes 2 and 3 solvents of International Conference of Harmonization (ICH) guideline Q3C, as residual solvents in drug substance. In order to increase the method sensitivity and efficiency in sample equilibration, dimethylsulfoxide (DMSO) was selected as the sample diluent based on its high capacity of dissolving drug substance, stability and high boiling point. The HS sample equilibration temperature and equilibration time are assessed in ranges of 125-150°C and 8-15 min, respectively. The results indicate that the residual solvents in 200mg of drug substance can be equilibrated efficiently in HS sampler at 140°C for 10 min. The GC parameters, e.g. sample split ratio, carrier flow rate and oven temperature gradient are manipulated to enhance the method sensitivity and separation efficiency. The two-stage gradient GC run from 35 to 240°C, using an Agilent DB-624 capillary column (30 m long, 0.32 mm I.D., 1.8 μm film thickness), is suitable to determine 44 ICH classes 2 and 3 solvents in 30 min. The method validation results indicate that the method is accurate, precise, linear and sensitive for solvents assessed. The recoveries of most of these solvents from four drug substances are greater than 80% within the method determination ranges. However, this method is not suitable for the 10 remaining ICH classes 2 and 3 solvents, because they are too polar (e.g. formic acid and acidic acid), or have boiling points higher than 150°C, (e.g. anisol and cumene). In comparison with the previous published methods, this method has a much shorter sample equilibration time, a better separation for many solvents, a higher sensitivity and a broader concentration range. PMID:20801455

  11. Protonation of a Glutamate Residue Modulates the Dynamics of the Drug Transporter EmrE

    PubMed Central

    Gayen, Anindita; Leninger, Maureen; Traaseth, Nathaniel J.

    2015-01-01

    Secondary active transport proteins play a central role in conferring bacterial multidrug resistance. In this work, we investigated the proton-coupled transport mechanism for the Escherichia coli drug efflux pump EmrE using nuclear magnetic resonance (NMR) spectroscopy. Our results show that the global conformational motions necessary for transport are modulated in an allosteric fashion by the protonation state of a membrane-embedded glutamate residue. These observations directly correlate with the resistance phenotype for EmrE and the E14D mutant as a function of pH. Furthermore, our results support a model in which the pH gradient across the inner membrane of E. coli may be used on a mechanistic level to shift the equilibrium of the transporter in favor of an inward-open resting conformation poised for drug binding. PMID:26751516

  12. Protonation of a glutamate residue modulates the dynamics of the drug transporter EmrE.

    PubMed

    Gayen, Anindita; Leninger, Maureen; Traaseth, Nathaniel J

    2016-03-01

    Secondary active transport proteins play a central role in conferring bacterial multidrug resistance. In this work, we investigated the proton-coupled transport mechanism for the Escherichia coli drug efflux pump EmrE using NMR spectroscopy. Our results show that the global conformational motions necessary for transport are modulated in an allosteric fashion by the protonation state of a membrane-embedded glutamate residue. These observations directly correlate with the resistance phenotype for wild-type EmrE and the E14D mutant as a function of pH. Furthermore, our results support a model in which the pH gradient across the inner membrane of E. coli may be used on a mechanistic level to shift the equilibrium of the transporter in favor of an inward-open resting conformation poised for drug binding. PMID:26751516

  13. EU sampling strategies for the detection of veterinary drug residues in aquaculture species: are they working?

    PubMed

    Morris, D J; Gray, A J; Kay, J F; Gettinby, G

    2012-08-01

    Over the past 50 years, the culture of aquatic species in controlled conditions to enhance production has grown in importance and now provides nearly 50% of the world's seafood supply. In part, this expansion has been made possible by the use of antibiotics, antifungals, and other veterinary medicines to control disease and improve welfare. Despite guidelines being available, the sampling programmes for drug residue surveillance of aquaculture products recommended by the CODEX Alimentarius Commission were withdrawn in 2008 and put under review. Directive 96/23/EC sets out legislation to govern how sampling programmes for drug residue surveillance should be conducted within the EU. This directive applies both to produce raised within the EU and also imported products from third countries. This communication examines the existing EU sampling regimen for aquaculture products and comments on its possible application in a global context. We examine UK statutory sampling data that, while indicating the effectiveness of the directive, also suggests that the directive may lead to unnecessary sampling. Regarding imports, examination of the Rapid Alert System for Food and Feed (RASFF) database using process control charts and statistical modelling suggests that the sampling regimen described in the directive is effective but not sufficiently flexible for the range of aquaculture practices that exist. Limitations of the directive, datasets, and practices are further discussed. PMID:22851354

  14. [Simple determination of residual anticoccidial drugs (diclazuril and nicarbazin) in chicken tissues by HPLC].

    PubMed

    Kanda, Maki; Ushiyama, Keiko; Igusa, Kyoko; Murayama, Mitsunori; Horie, Masakazu; Hirokado, Masako; Miyazaki, Tomoyuki

    2003-04-01

    A simple and rapid determination of anticoccidial drug residues, diclazuril (DCZ) and nicarbazin (NCZ), in chicken tissues has been developed. DCZ and NCZ were extracted with acetonitrile from chicken liver, muscle, and fat. The extract was rinsed with n-hexane saturated with acetonitrile and then evaporated. The residue was dissolved in 1.4 mL of acetonitrile-methanol (1:1), then 1.0 mL of n-hexane saturated with acetonitrile-methanol (1:1) was added, and the mixture was partitioned by the addition of 0.6 mL of water. DCZ and NCZ in the aqueous layers were determined by HPLC on an Xterra RP-18 column with acetonitrile-0.5% ammonium acetate containing 0.01 mol/L tetra-n-butylammonium hydrogen sulfate (43:57) as the mobile phase. The mean recoveries (n = 5) of DCZ and NCZ spiked in chicken tissues at the maximum residue levels were 92.0-95.6% (CV 2.4-3.0%) and 87.3-89.4% (CV 1.7-2.8%), respectively. The detection limits of DCZ and NCZ were 0.01 and 0.004 microgram/g, respectively. PMID:12846158

  15. Veterinary drug residues in seafood inspected by the European Union, United States, Canada, and Japan from 2000 to 2009.

    PubMed

    Love, David C; Rodman, Sarah; Neff, Roni A; Nachman, Keeve E

    2011-09-01

    Veterinary drugs are used to treat or prevent a wide array of production-related diseases in aquaculture. Residues of these drugs in seafood products may pose risks to consumers, prompting governments to set drug residue tolerance levels and inspect seafood for violations of these standards. This study characterizes veterinary drug inspection policies and violations among four inspecting bodies (European Union (E.U.), United States (U.S.), Canada, and Japan), using government-collected veterinary drug violation data from 2000 to 2009. Most veterinary drug violations were detected in species that are commonly farm-raised. Asian seafood products, including shrimp and prawns, catfish (or fish sold as catfish), crab, tilapia, eel, and Chilean salmon were most frequently in violation of veterinary drug residue standards. Vietnam had the greatest number of violations among exporting countries. Concentrations of most veterinary drugs in seafood found in violation did not differ between inspecting bodies that reported drug concentrations. Transparency in seafood inspection reporting varied widely among inspecting bodies. Estimation of violations in the untested fraction of seafood was precluded by a lack of information from inspecting bodies regarding the distinction between targeted and random sampling. Increased transparency could facilitate a more rigorous characterization of public health risks from consuming imported seafood. PMID:21797221

  16. Determination of macrocyclic lactone drug residues in animal muscle by liquid chromatography/tandem mass spectrometry.

    PubMed

    He, Limin; Zhao, Donghao; Su, Yijuan; Liu, Yahong; Nie, Jianrong; Lian, Jin

    2009-01-01

    A robust, credible, and practical multiresidue method based on liquid chromatography/tandem/mass spectrometry (LC/MS/MS) was developed for the simultaneous determination of 9 macrocyclic lactone drugs (abamectin B1a, doramectin, erythromycin, ivermectin B1a, josamycin, kitasamycin, roxithromycin, tilmicosin, and tylosin A) in bovine, porcine, chicken, and sheep muscles. The drugs were extracted with acetonitrile, and the extracts were defatted with n-hexane and further cleaned up on a C18 solid-phase extraction cartridge. LC/MS/MS data acquisition was achieved by using the multiple-reaction monitoring (MRM) mode, i.e., 2 transitions, to provide a high degree of sensitivity and repeatability. Matrix-matched standard calibration curves were used to achieve the best accuracy of the method by compensating for the matrix effect. The calibration graphs were linear (r > 0.998) from 10 to 1000 ng/mL for erythromycin, josamycin, kitasamycin, roxithromycin, tilmicosin, and tylosin, and from 5 to 250 ng/mL for abamectin, doramectin, and ivermectin. The average recoveries of the 9 drugs were between 64.5 and 105%, calculated by using matrix-matched calibration, with relative standard deviation values ranging from 1.6 to 14%. The limits of detection were 0.1 microg/kg for erythromycin, josamycin, roxithromycin, and tylosin; 0.2 microg/kg for tilmicosin and kitasamycin; and 0.5 microg/kg for abamectin, doramectin, and ivermectin. For confirmation, the MRM ratios for the 9 drug residues in the samples and the solvent were evaluated and found to be within the ratio criteria set by the guidelines of the European Union. PMID:19382593

  17. Dielectric properties of residual water in amorphous lyophilized mixtures of sugar and drug

    NASA Astrophysics Data System (ADS)

    El Moznine, R.; Smith, G.; Polygalov, E.; Suherman, P. M.; Broadhead, J.

    2003-02-01

    Dielectric relaxation spectroscopy was used to investigate the properties of residual water in lyophilized formulations of a proprietary tri-phosphate drug containing a sugar (trehalose, lactose or sucrose) or dextran. The dielectric properties of each formulation were determined in the frequency range (0.1 Hz-0.1 MHz) and temperature range (30°C-Tg). The temperature dependence of the relaxation times for all samples showed Arrhenuis behaviour, from which the activation energy was derived. Proton hopping through the hydrogen-bonded network (clusters) of water molecules was suggested as the principle mode of charge transport. Significant differences in dielectric relaxation kinetics and activation energy were observed for the different formulations, which were found to correlate with the amount of monophosphate degradation product.

  18. Immunology-Based Techniques for the Detection of Veterinary Drug Residues in Foods

    NASA Astrophysics Data System (ADS)

    Reig, Milagro; Toldrá, Fidel

    Veterinary drugs are used in farm animals, via the feed or the drinking water, to prevent the outbreak of diseases or even for the treatment of diseases. However, the growth of animals may be promoted through the use of hormones and antibiotics. Depending on the type of residue and the application and washing conditions, these substances or its metabolites may remain in meat and other foods of animal origin and may cause adverse effects on consumers’ health. This is the main reason why its use is strictly regulated or even banned (case of the European Union) in different countries. Antibiotics typically used for growth promotion include chloramphenicol, nitrofurans, and enrofloxacin but others like sulphonamides, macrolides etc. may also be used (Reig & Toldrá, 2007).

  19. Simultaneous and rapid detection of multiple pesticide and veterinary drug residues by suspension array technology.

    PubMed

    Liu, Nan; Gao, Zhixian; Ma, Hongwei; Su, Pu; Ma, Xinhua; Li, Xiaoli; Ou, Guorong

    2013-03-15

    Suspension array technology is proposed for the simultaneous quantitative determination of seven kinds of pesticide and veterinary drug residues, namely, atrazine, chloramphenicol, carbaryl, clenbuterol, 17-β-estradiol, imidacloprid, and tylosin. The assay is simple and can be accomplished within 2h without repeated pumping and washing steps unlike conventional suspension arrays. The hapten-protein conjugate-coated beads bind to their complementary biotinylated antibodies using a competitive immunoassay format. The coefficients of determination R(2) for six targets were greater than 0.992, whereas that for atrazine was 0.961, which indicate good logistic correlations. The dynamic ranges for the seven targets in the 7-plex assay ranged from 2 log units to 4 log units(1.60×10(0)-1.64×10(3), 5.12×10(-2)-1.60×10(2), 1.00×10(0)-3.13×10(3), 4.00×10(-1)-4.10×10(2), 4.00×10(-1)-4.10×10(2), 5.12×10(-2)-1.60×10(2), and 2.00×10(0)-4.00×10(2)ngmL(-1)). The minimum detection concentrations of chloramphenicol, carbaryl, clenbuterol and 17-β-estradiol in the suspension array (0.05, 1.00, 0.40 and 0.40 ng mL(-1)) were lower than the corresponding limits of detection (0.25, 6.60, 24.23 and 13.96 ng mL(-1)) of using an indirect competitive enzyme-linked immunosorbent assay. Environmental scanning electron microscope was employed to characterize the bead surface, which directly confirmed the reactions on the beads. The suspension array is more flexible and feasible than ELISA for the fast quantitative analysis of pesticide and veterinary drug residues. PMID:23084755

  20. The effect of cooking on veterinary drug residues in food: 4. Oxytetracycline.

    PubMed

    Rose, M D; Bygrave, J; Farrington, W H; Shearer, G

    1996-04-01

    The heat stability of oxytetracycline (OTC) in water and vegetable oil was investigated. Results showed that the drug was unstable in water at 100 degrees C with a half-life of about 2 min, but more stable in oil at 180 degrees C where the half-life was about 8 min. The effect of a range of cooking processes including microwaving, boiling, roasting, grilling, braising and frying on OTC residues in incurred animal tissues was investigated. Substantial net reductions in OTC of 35-94% were observed, with temperature during cooking having the largest impact on the loss. Migration from the tissue into the surrounding liquid or meat juices was observed during the cooking processes. Diode-array analysis of heat-treated OTC standard solutions indicated that no individual closely related compound such as 4-epioxytetracycline, alpha- or beta-apooxytetracycline formed a significant proportion of the breakdown products. OTC was not evenly distributed throughout the tissue, but the effects of this were minimized by selecting adjacent samples for cooking and for the raw control. The findings of this investigation showed that the effect of cooking on residues of OTC should be considered before data obtained from measurements on raw tissue are used for consumer exposure estimates and dietary intake calculations. PMID:8718742

  1. A direct droplet digital PCR method for quantification of residual DNA in protein drugs produced in yeast cells.

    PubMed

    Hussain, Musaddeq; Fantuzzo, Rebecca; Mercorelli, Suzanne; Cullen, Constance

    2016-05-10

    Yeast cells, in particular Pichia pastoris, are the host cell of choice for manufacturing several protein therapeutic agents in the biopharmaceutical industry. Host cell DNA is an impurity of such manufacturing process and the residual DNA after the purification process of the drug must be monitored to ensure drug purity and safety. Currently, real-time PCR (qPCR) based methods are widely employed for quantification of host residual DNA. At the same time the digital PCR technology is coming into prominence with promise of higher sensitivity. Here we report a method where the protein drug is directly added to the droplet digital PCR (ddPCR) reaction including yeast-specific primers and fluorescent-tagged probe and nanoliter-sized droplets are generated. The droplets are then subjected to PCR followed by analysis for fluorescence. This Pichia residual DNA direct ddPCR method for yeast can be used to test higher amount of drug compared to the corresponding qPCR method thereby increasing sensitivity, retaining high precision and accuracy and has a wide linear range of determination. The method has been successfully tested with three batches of a recombinant human IgG1-Fc-based drug (RP-1) and with commercially available human insulin, both manufactured in yeast cells. This method simplifies the residual DNA quantification protocol by eliminating DNA extraction or protease digestion and eliminates use of DNA standards in day-to-day running of the method. PMID:26896631

  2. Fourier transform infared spectroscopic imaging for the identification of concealed drug residue particles and fingerprints

    NASA Astrophysics Data System (ADS)

    Ricci, Camilla; Chan, K. L. Andrew; Kazarian, Sergei G.

    2006-09-01

    Conventional FTIR spectroscopy and microscopy has been widely used in forensic science. New opportunities exist to obtain rapid chemical images and to enhance the sensitivity of detection of trace materials using attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy coupled with a focal-plane array (FPA) detector. In this work, the sensitivity of ATR-FTIR spectroscopic imaging using three different kinds of ATR crystals (Ge coupled with an infrared microscope, ZnSe and diamond) and resulting in three different optical arrangements for the detection of model drug particles is discussed. Model systems of ibuprofen and paracetamol particles having a size below 32 micrometers have been prepared by sieving. The sensitivity level in the three different approaches has been compared and it has been found that both micro and macro-ATR imaging methods have proven to be a promising techniques for the identification of concealed drug particles. To demonstrate the power and applicability of FTIR chemical imaging to forensic research, various examples are discussed. This includes investigation of the changes of chemical nature of latent fingerprint residue under controlled conditions of humidity and temperature studied by ATR-FTIR imaging. This study demonstrates the potential of spectroscopic imaging for visualizing the chemical changes of fingerprints.

  3. Comparison of different agar diffusion methods for the detection of residues in the kidneys of pigs treated with antimicrobial drugs.

    PubMed

    Korkeala, H; Sorvettula, O; Mäki-Petäys, O; Hirn, J

    1983-01-01

    Residue analyses of the kidneys of twenty-six pigs treated with various antimicrobial drugs 20 h before slaughter and of eleven untreated pigs were performed. The effects of storage temperature of the kidneys, and of sampling location, on the residue analysis were also studied. No method alone was sufficient for the detection of residues. Oxytetracycline residues could be detected at pH 6, dihydrostreptomycin residues at pH 8, and sulphonamide residues if trimethoprim was present in the medium. Chloramphenicol, penicillin G procaine, tylosin and lincomycin residues were not detectable with the methods used. The concentration of ampicillin decreased during the storage of samples at +4°C. Most methods also yielded zones of inhibition for the frozen kidneys from untreated pigs. It seems necessary to use agar media of two different pH values: the addition of trimethoprim to the medium is also needed. The use of fresh pig kidneys, and samples containing both kidney medulla and kidney cortex, is recommended in residue analysis. PMID:22055926

  4. 77 FR 16806 - Codex Alimentarius Commission: Meeting of the Codex Committee on Residues of Veterinary Drugs in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-22

    ... from FAO/WHO and from the 75th Meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA... Food Safety and Inspection Service Codex Alimentarius Commission: Meeting of the Codex Committee on Residues of Veterinary Drugs in Food AGENCY: Office of the Under Secretary for Food Safety, USDA....

  5. 75 FR 48928 - Codex Alimentarius Commission: Meeting of the Codex Committee on Residues of Veterinary Drugs in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-12

    ... requiring evaluation or re-evaluation by the Joint FAO/WHO Expert Committee on Food Additives (JECFA... Food Safety and Inspection Service Codex Alimentarius Commission: Meeting of the Codex Committee on Residues of Veterinary Drugs in Food AGENCY: Office of the Acting Under Secretary for Food Safety,...

  6. 21 CFR 556.1 - General considerations; tolerances for residues of new animal drugs in food.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... drug, has been shown to induce cancer in man or animal; however, such drug will not adversely affect... new animal drugs in food. 556.1 Section 556.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES...

  7. 21 CFR 556.1 - General considerations; tolerances for residues of new animal drugs in food.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... drug, has been shown to induce cancer in man or animal; however, such drug will not adversely affect... new animal drugs in food. 556.1 Section 556.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES...

  8. 21 CFR 556.1 - General considerations; tolerances for residues of new animal drugs in food.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... drug, has been shown to induce cancer in man or animal; however, such drug will not adversely affect... new animal drugs in food. 556.1 Section 556.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES...

  9. 21 CFR 556.1 - General considerations; tolerances for residues of new animal drugs in food.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... drug, has been shown to induce cancer in man or animal; however, such drug will not adversely affect... new animal drugs in food. 556.1 Section 556.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES...

  10. Determination of pesticides and veterinary drug residues in food by liquid chromatography-mass spectrometry: A review.

    PubMed

    Masiá, Ana; Suarez-Varela, Maria Morales; Llopis-Gonzalez, Agustin; Picó, Yolanda

    2016-09-14

    Monitoring of pesticides and veterinary drug residues is required to enforce legislation and guarantee food safety. Liquid chromatography-mass spectrometry (LC-MS) is the prevailing technique for assessing both types of residues because LC offers a versatile and universal separation mechanism suitable for non-gas chromatography (GC) amenable and the majority of GC-amenable compounds. This characteristic becomes more relevant when LC is coupled to MS because the high sensitivity and specificity of the detector allows to apply generic sample preparation procedures, which simultaneously extract a wide variety of residues with different physico-chemical properties. Determination of metabolites and degradation products, non-target suspected screening of an increasing number of residues, and even unknowns identification are also becoming inherent LC-MS advantages thanks to the latest advances. For routine analysis and, in particular, for official surveillance purposes in food control, analytical methods properly validated following strict guidelines are needed. After a brief introduction and an outline of the legislation applicable around the world, aspects such as improvement of specificity of high-throughput methods, resolution and mass accuracy of identification strategies and quantitative accuracy are critically reviewed in this article. In them, extraction, separation and determination are emphasized. The main objective is to offer an assessment of the state of the art and identify research needs and future trends in determining pesticide and veterinary drug residues in food by LC-MS. PMID:27566339

  11. A direct qPCR method for residual DNA quantification in monoclonal antibody drugs produced in CHO cells.

    PubMed

    Hussain, Musaddeq

    2015-11-10

    Chinese hamster ovary (CHO) cells are the host cell of choice for manufacturing of monoclonal antibody (mAb) drugs in the biopharmaceutical industry. Host cell DNA is an impurity of such manufacturing process and must be controlled and monitored in order to ensure drug purity and safety. A conventional method for quantification of host residual DNA in drug requires extraction of DNA from the mAb drug substance with subsequent quantification of the extracted DNA using real-time PCR (qPCR). Here we report a method where the DNA extraction step is eliminated prior to qPCR. In this method, which we have named 'direct resDNA qPCR', the mAb drug substance is digested with a protease called KAPA in a 96-well PCR plate, the protease in the digest is then denatured at high temperature, qPCR reagents are added to the resultant reaction wells in the plate along with standards and controls in other wells of the same plate, and the plate subjected to qPCR for analysis of residual host DNA in the samples. This direct resDNA qPCR method for CHO is sensitive to 5.0fg of DNA with high precision and accuracy and has a wide linear range of determination. The method has been successfully tested with four mAbs drug, two IgG1 and two IgG4. Both the purified drug substance as well as a number of process intermediate samples, e.g., bioreactor harvest, Protein A column eluate and ion-exchange column eluates were tested. This method simplifies the residual DNA quantification protocol, reduces time of analysis and leads to increased assay sensitivity and development of automated high-throughput methods. PMID:25850374

  12. Identification of residues in the drug translocation pathway of the human multidrug resistance P-glycoprotein by arginine mutagenesis.

    PubMed

    Loo, Tip W; Bartlett, M Claire; Clarke, David M

    2009-09-01

    P-glycoprotein (P-gp, ATP-binding cassette B1) is a drug pump that extracts toxic drug substrates from the plasma membrane and catalyzes their ATP-dependent efflux. To map the residues in the drug translocation pathway, we performed arginine-scanning mutagenesis on all transmembrane (TM) segments (total = 237 residues) of a P-gp processing mutant (G251V) defective in folding (15% maturation efficiency) (glycosylation state used to monitor folding). The rationale was that arginines introduced into the drug-binding sites would mimic drug rescue and enhance maturation of wild-type or processing mutants of P-gp. It was found that 38 of the 89 mutants that matured had enhanced maturation. Enhancer mutations were found in 11 of the 12 TM segments with the largest number found in TMs 6 and 12 (seven in each), TMs that are critical for P-gp-drug substrate interactions. Modeling of the TM segments showed that the enhancer arginines were found on the hydrophilic face, whereas inhibitory arginines were located on a hydrophobic face that may be in contact with the lipid bilayer. It was found that many of the enhancer arginines caused large alterations in P-gp-drug interactions in ATPase assays. For example, mutants A302R (TM5), L339R (TM6), G872R (TM10), F942R (TM11), Q946R (TM11), V982R (TM12), and S993R (TM12) reduced the apparent affinity for verapamil by approximately 10-fold, whereas the F336R (TM6) and M986R (TM12) mutations caused at least a 10-fold increase in apparent affinity for rhodamine B. The results suggest that P-gp contains a large aqueous-filled drug translocation pathway with multiple drug-binding sites that can accommodate the bulky arginine side chains to promote folding of the protein. PMID:19581304

  13. A multi-residue method for the determination of seven polypeptide drug residues in chicken muscle tissues by LC-MS/MS.

    PubMed

    Boison, Joe O; Lee, Stephen; Matus, Johanna

    2015-05-01

    A new multi-residue method for the determination of seven polypeptides, namely, polymixin B1, polymixin B2, polymixin E1 (colistin A), polymixin E2 (colistin B), enduracidin A (enramycin A), enduracidin B (enramycin B), and bacitracin A, in food of animal origin was developed and validated for chicken muscle tissue. Chicken muscle tissue was extracted with acidified methanol (1 % TFA). After homogenization, shaking, and centrifugation, the acidified methanol extract was decanted. A second extraction was performed with methanol (1 % TFA) and formic acid (1 %) 25:75, v/v. The pooled extract was cleaned up and concentrated on a solid-phase extraction cartridge. The retained analytes were eluted with methanol/acetonitrile. The extract was evaporated to dryness, reconstituted in mobile phase, filtered, and quantified by LC-MS/MS under ESI conditions. The method has a LOQ of 50.0 μg/kg for polymixin E2 (colistin B), 39.0 μg/kg for polymixin E1 (colistin A), 74.0 μg/kg for polymixin B1, 71.0 μg/kg for polymixin B2, 66.0 μg/kg for enduracidin A, 50.0 μg/kg for enduracidin B, and 30.0 μg/kg for bacitracin A in chicken muscle tissues. This is the first sensitive, suitable, multi-residue method reported for the seven polypeptide drug residues in chicken muscle tissue. PMID:25832483

  14. Distribution of phthalates, pesticides and drug residues in the dissolved, particulate and sedimentary phases from transboundary rivers (France-Belgium).

    PubMed

    Net, Sopheak; Rabodonirina, Suzanah; Sghaier, Rafika Ben; Dumoulin, David; Chbib, Chaza; Tlili, Ines; Ouddane, Baghdad

    2015-07-15

    Various drug residues, pesticides and phthalates are ubiquitous in the environment. Their presence in the environment has attracted considerable attention due to their potential impacts on ecosystem functioning and on public health. In this work, 14 drug residues, 24 pesticides and 6 phthalates have been quantified in three matrices (in the dissolved phase, associated to suspended solid matter (SSM), and in sediment) collected from fifteen watercourses and rivers located in a highly industrialized zone at the cross-border area of Northern France and Belgium. The extractions have been carried out using accelerated solvent extraction (ASE) for solid matrices (SSM and sediment) and using solid phase extraction (SPE) for liquid matrix. The final extract was analyzed using GC-MS technique. Among the three classes of compounds, phthalates have been found at highest level compared to pesticides and drug residues. The Σ6PAE concentrations were ranging from 17.2±2.58 to 179.1±26.9μgL(-1) in dissolved phase, from 2.9±0.4 to 21.1±3.2μgL(-1) in SSM and from 1.1±0.2 to 11.9±1.8μgg(-1)dw in sediment. The Σ14drug residue concentrations were lower than 1.3μgL(-1) in the dissolved phases, lower than 30ngL(-1) associated to SSM and from nondetectable levels to 60.7±9.1ngg(-1)dw in sediment. For pesticides, all compounds were below the LOQ values in dissolved phase and in sediment, and only EPTC could be quantified in SSM. PMID:25829293

  15. Evaluation of certain veterinary drug residues in food. Sixty-second report of the Joint FAO/WHO Expert Committee on food additives.

    PubMed

    2004-01-01

    This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers conclusions on specific toxicological end-points, lipid-soluble residues of veterinary drugs with MRLs in milk, statistical methods for the estimation of MRLs, and the Committee's review and comments on documents provided by Codex Committees. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: five antibacterial agents (cefuroxime, chloramphenicol, flumequine, lincomycin, pirlimycin), four insecticides (cyhalothrin, cypermethrin and alpha-cypermethrin, doramectin, phoxim), and two production aids (melengestrol acetate, ractopamine). The Committee's comments on chloramphenicol found at low levels in animal products are also summarized. Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes and proposed maximum residue limits. PMID:15587045

  16. Analytical method for simultaneous determination of pesticide and veterinary drug residues in milk by CE-MS.

    PubMed

    Blasco, Cristina; Picó, Yolanda; Andreu, Vicente

    2009-05-01

    This study reports a method based on CE-MS/MS detection developed for the multiresidue determination of seven pesticides (amidosulfuron, cyprodinil, cyromazine, imazaquin, pirimicarb, demethyl pirimicarb, procymidone) and eight residues of veterinary drugs (ciprofloxacin, enrofloxacin, sulfacetamide, sulfabenzamide, sulfachlorpyridazine, sulfaquinoxaline, sulfathiazole, sulfisoxazole), whose contents are regulated by the EU Council Regulations no. 396/2005 and no. 2377/90, in animal edible tissues. Milk samples were extracted with ACN and the extract was cleaned up using an Oasis hydrophilic-lipophilic balance SPE cartridge. The proposed method was validated in accordance with the European Commission Decision 657/2002. MS/MS experiments, using an IT analyzer, operating in multiple reaction monitoring mode, were carried out to achieve the minimum number of required identification points. Recovery data were also satisfactory, with values higher than 78% for most pesticides and veterinary drugs extracted from milk spiked at half the maximum residue limit established for the studied compounds. The RSD% (n = 5) were lower than 13 and 15% for intra-day and inter-day assays, respectively. The method was applied to establish the occurrence of the studied pesticides in 100 milk samples, attaining the determination of pesticide and veterinary drug residues in milk in the low microg/kg range. PMID:19384986

  17. Surface wipe sampling for antineoplastic (chemotherapy) and other hazardous drug residue in healthcare settings: Methodology and recommendations.

    PubMed

    Connor, Thomas H; Zock, Matthew D; Snow, Amy H

    2016-09-01

    Surface wipe sampling for various hazardous agents has been employed in many occupational settings over the years for various reasons such as evaluation of potential dermal exposure and health risk, source determination, quality or cleanliness, compliance, and others. Wipe sampling for surface residue of antineoplastic and other hazardous drugs in healthcare settings is currently the method of choice to determine surface contamination of the workplace with these drugs. The purpose of this article is to review published studies of wipe sampling for antineoplastic and other hazardous drugs, to summarize the methods in use by various organizations and researchers, and to provide some basic guidance for conducting surface wipe sampling for these drugs in healthcare settings.  Recommendations on wipe sampling methodology from several government agencies and organizations were reviewed. Published reports on wipe sampling for hazardous drugs in numerous studies were also examined. The critical elements of a wipe sampling program and related limitations were reviewed and summarized.  Recommendations and guidance are presented concerning the purposes of wipe sampling for antineoplastic and other hazardous drugs in the healthcare setting, technical factors and variables, sampling strategy, materials required, and limitations. The reporting and interpretation of wipe sample results is also discussed.  It is recommended that all healthcare settings where antineoplastic and other hazardous drugs are handled consider wipe sampling as part of a comprehensive hazardous drug "safe handling" program. Although no standards exist for acceptable or allowable surface concentrations for these drugs in the healthcare setting, wipe sampling may be used as a method to characterize potential occupational dermal exposure risk and to evaluate the effectiveness of implemented controls and the overall safety program. A comprehensive safe-handling program for antineoplastic drugs may

  18. Multi-residue determination of 210 drugs in pork by ultra-high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Yin, Zhiqiang; Chai, Tingting; Mu, Pengqian; Xu, Nana; Song, Yue; Wang, Xinlu; Jia, Qi; Qiu, Jing

    2016-09-01

    This paper presents a multi-residue analytical method for 210 drugs in pork using ultra-high-performance liquid chromatography-Q-Trap tandem mass spectrometry (UPLC-MS/MS) within 20min via positive ESI in scheduled multi-reaction monitoring (MRM) mode. The 210 drugs, belonging to 21 different chemical classes, included macrolides, sulfonamides, tetracyclines, β-lactams, β-agonists, aminoglycosides, antiviral drugs, glycosides, phenothiazine, protein anabolic hormones, non-steroidal anti-inflammatory drugs (NSAIDs), quinolones, antifungal drugs, corticosteroids, imidazoles, piperidines, piperazidines, insecticides, amides, alkaloids and others. A rapid and simple preparation method was applied to process the animal tissues, including solvent extraction with an acetonitrile/water mixture (80/20, v/v), defatting and clean-up processes. The recoveries ranged from 52% to 130% with relative standard deviations (RSDs)<20% for spiked concentrations of 10, 50 and 250μg/kg. More than 90% of the analytes achieved low limits of quantification (LOQs)<10μg/kg. The decision limit (CCα), detection capability (CCβ) values were in the range of 2-502μg/kg and 4-505μg/kg, respectively. This method is significant for food safety monitoring and controlling veterinary drug use. PMID:27499107

  19. Multi-residue determination of 115 veterinary drugs and pharmaceutical residues in milk powder, butter, fish tissue and eggs using liquid chromatography-tandem mass spectrometry.

    PubMed

    Dasenaki, Marilena E; Thomaidis, Nikolaos S

    2015-06-23

    A simple and sensitive multi-residue method for the determination of 115 veterinary drugs and pharmaceuticals, belonging in more than 20 different classes, in butter, milk powder, egg and fish tissue has been developed. The method involves a simple generic solid-liquid extraction step (solvent extraction, SE) with 0.1% formic acid in aqueous solution of EDTA 0.1% (w/v)-acetonitrile (ACN)-methanol (MeOH) (1:1:1, v/v) with additional ultrasonic-assisted extraction. Precipitation of lipids and proteins was promoted by subjecting the extracts at very low temperature (-23°C) for 12h. Further cleanup with hexane ensures fat removal from the matrix. Analysis was performed by liquid chromatography coupled with electrospray ionization and tandem mass spectrometry (LC-ESI-MS/MS). Two separate runs were performed for positive and negative ionization in multiple reaction monitoring mode (MRM). Particular attention was devoted to extraction optimization: different sample-to-extracting volume ratios, different concentrations of formic acid in the extraction solvent and different ultrasonic extraction temperatures were tested in butter, egg and milk powder samples. The method was also applied in fish tissue samples. It was validated, on the basis of international guidelines, for all four matrices. Quantitative analysis was performed by means of standard addition calibration. For over 80% of the analytes, the recoveries were between 50% and 120% in all matrices studied, with RSD values in the range of 1-18%. Limits of detection (LODs) and quantification (LOQs) ranged from 0.008 μg kg(-1) (oxfendazole in butter) to 3.15 μg kg(-1) (hydrochlorthiazide in egg). The evaluated method provides reliable screening, quantification, and identification of 115 veterinary drug and pharmaceutical residues in foods of animal origin and has been successfully applied in real samples. PMID:26092343

  20. Evaluation of certain veterinary drug residues in food. Fiftieth report of the joint FAO/WHO Expert Committee on Food Additives.

    PubMed

    1999-01-01

    This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues. The first part of the report considers the neurotoxicity of anthelminthics belonging to the avermectin and milbemycin classes of compounds and the evaluation policy of the Committee in establishing Maximum Residue Levels (MRLs) for veterinary drugs in food. A summary follows of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: five anthelminthic agents (eprinomectin, febantel, fenbendazole, oxfendazole and moxidectin), seven antimicrobial agents (gentamicin, procaine benzylpenicillin, sarafloxacin, spectinomycin, chlortetracycline, oxytetracycline and tetracycline), three antiprotozoal agents (diclazuril, imidocarb and nicarbazin), one glucocorticosteroid (dexamethasone), one production aid (recombinant bovine somatotropins) and one tranquilizing agent (azaperone). Annexed to the report are a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and MRLs, and further toxicological studies and other information required. PMID:10416362

  1. Development and validation of a streamlined method designed to detech residues of 62 veterinary drugs in bovine kidney using ultrahigh performance liquid chromatography - tandem mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the USA, the US Department of Agriculture’s Food Safety Inspection Service (FSIS) conducts the National Residue Program designed to monitor veterinary drug and other chemical residues in beef and other slaughtered food animals. Currently, FSIS uses a 7-plate bioassay in the laboratory to screen f...

  2. Access channel residues Ser315 and Asp137 in Mycobacterium tuberculosis catalase-peroxidase (KatG) control peroxidatic activation of the pro-drug isoniazid

    PubMed Central

    Zhao, Xiangbo; Hersleth, Hans-Petter; Zhu, Janan; Andersson, K. Kristoffer; Magliozzo, Richard S.

    2013-01-01

    Peroxidatic activation of the anti-tuberculosis pro-drug isoniazid by Mycobacterium tuberculosis catalase-peroxidase (KatG) is regulated by gating residues of a heme access channel. The steric restriction at the bottleneck of this channel is alleviated by replacement of residue Asp137 with Ser, according to crystallographic and kinetic studies. PMID:24185282

  3. Evaluation of certain veterinary drug residues in food. Eighty-first report of the Joint FAO/WHO Expert Committee on Food Additives.

    PubMed

    2016-01-01

    This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers general principles regarding the evaluation of residues of veterinary drugs within the terms of reference of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), including MRLs for generic fish species, acute reference doses (ARfDs) for veterinary drugs, an approach for dietary exposure assessment of compounds used for multiple purposes (i.e veterinary drugs and pesticides), dietary exposure assessment for less-than-lifetime exposure, and the assessment of short-term (90-day and 12-month) studies in dogs. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: two insecticides (diflubenzuron and teflubenzuron), an antiparasitic agent (ivermectin), an ectoparasiticide (sisapronil) and a β2-adrenoceptor agonist (zilpaterol hydrochloride). In addition, the Committee considered issues raised in concern forms from the Codex Committee on Residues of Veterinary Drugs in Foods on lasalocid sodium, an antiparasitic agent. Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes (ADIs), ARfDs and proposed MRLs. PMID:27509597

  4. Drug residues recovered in feed after various feedlot mixer truck cleanout procedures.

    PubMed

    Van Donkersgoed, Joyce; Sit, Dan; Gibbons, Nicole; Ramogida, Caterina; Hendrick, Steve

    2010-01-01

    A study was conducted to determine the effectiveness of two methods of equipment cleanout, sequencing or flushing, for reducing drug carryover in feedlot mixer trucks. Feed samples were collected from total mixed rations before and after various feed mixer equipment cleanout procedures. Medicated rations contained either 11 ppm of tylosin or 166 or 331 ppm of chlortetracycline. There were no differences between sequencing and flushing or between flushing with dry barley and flushing with barley silage in the median proportion of drug recovered in the next ration. A larger drug reduction was achieved using flush material at a volume of 10 versus 5% of the mixer capacity and mixing the flush material for 3 versus 4 min. Regardless of the drug or prescription concentrations in the total mixed rations or the equipment cleanout procedure used, concentrations of chlortetracycline and tylosin recovered were very low. PMID:20051207

  5. Simultaneous screening and confirmation of multiple classes of drug residues in fish by liquid chromatography-ion trap mass spectrometry.

    PubMed

    Smith, Shani; Gieseker, Charles; Reimschuessel, Renate; Decker, Christie-Sue; Carson, Mary C

    2009-11-13

    LC-ion trap mass spectrometry was used to screen and confirm 38 compounds from a variety of drug classes in four species of fish: trout, salmon, catfish, and tilapia. Samples were extracted with acetonitrile and hexane. The acetonitrile phase was evaporated, redissolved in water and acetonitrile, and analyzed by gradient chromatography on a phenyl column. MS(2) or MS(3) spectra were monitored for each compound. Qualitative method performance was evaluated by the analysis over several days of replicate samples of control fish, fish fortified with a drug mixture at 1 ppm, 0.1 ppm and 0.01 ppm, and fish dosed with a representative from each drug class. Half of the 38 drugs were confirmed at 0.01 ppm, the lowest fortification level. This included all of the quinolones and fluoroquinolones, the macrolides, malachite green, and most of the imidazoles. Florfenicol amine, metronidazole, sulfonamides, tetracyclines, and most of the betalactams were confirmed at 0.1 ppm. Ivermectin and penicillin G were only detectable in the 1 ppm fortified samples. With the exception of amoxicillin, emamectin, metronidazole, and tylosin, residue presence was confirmed in all the dosed fish. PMID:19616215

  6. Global connectivity of hub residues in Oncoprotein structures encodes genetic factors dictating personalized drug response to targeted Cancer therapy

    PubMed Central

    Soundararajan, Venky; Aravamudan, Murali

    2014-01-01

    The efficacy and mechanisms of therapeutic action are largely described by atomic bonds and interactions local to drug binding sites. Here we introduce global connectivity analysis as a high-throughput computational assay of therapeutic action – inspired by the Google page rank algorithm that unearths most “globally connected” websites from the information-dense world wide web (WWW). We execute short timescale (30 ps) molecular dynamics simulations with high sampling frequency (0.01 ps), to identify amino acid residue hubs whose global connectivity dynamics are characteristic of the ligand or mutation associated with the target protein. We find that unexpected allosteric hubs – up to 20Å from the ATP binding site, but within 5Å of the phosphorylation site – encode the Gibbs free energy of inhibition (ΔGinhibition) for select protein kinase-targeted cancer therapeutics. We further find that clinically relevant somatic cancer mutations implicated in both drug resistance and personalized drug sensitivity can be predicted in a high-throughput fashion. Our results establish global connectivity analysis as a potent assay of protein functional modulation. This sets the stage for unearthing disease-causal exome mutations and motivates forecast of clinical drug response on a patient-by-patient basis. We suggest incorporation of structure-guided genetic inference assays into pharmaceutical and healthcare Oncology workflows. PMID:25465236

  7. Global connectivity of hub residues in Oncoprotein structures encodes genetic factors dictating personalized drug response to targeted Cancer therapy

    NASA Astrophysics Data System (ADS)

    Soundararajan, Venky; Aravamudan, Murali

    2014-12-01

    The efficacy and mechanisms of therapeutic action are largely described by atomic bonds and interactions local to drug binding sites. Here we introduce global connectivity analysis as a high-throughput computational assay of therapeutic action - inspired by the Google page rank algorithm that unearths most ``globally connected'' websites from the information-dense world wide web (WWW). We execute short timescale (30 ps) molecular dynamics simulations with high sampling frequency (0.01 ps), to identify amino acid residue hubs whose global connectivity dynamics are characteristic of the ligand or mutation associated with the target protein. We find that unexpected allosteric hubs - up to 20Å from the ATP binding site, but within 5Å of the phosphorylation site - encode the Gibbs free energy of inhibition (ΔGinhibition) for select protein kinase-targeted cancer therapeutics. We further find that clinically relevant somatic cancer mutations implicated in both drug resistance and personalized drug sensitivity can be predicted in a high-throughput fashion. Our results establish global connectivity analysis as a potent assay of protein functional modulation. This sets the stage for unearthing disease-causal exome mutations and motivates forecast of clinical drug response on a patient-by-patient basis. We suggest incorporation of structure-guided genetic inference assays into pharmaceutical and healthcare Oncology workflows.

  8. Evaluation of certain veterinary drug residues in food. Sixty-sixth report of the Joint FAO/WHO Expert Committee on Food Additives.

    PubMed

    2006-01-01

    This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers general principles regarding the evaluation of veterinary drugs within the terms of reference of JECFA, including compounds without an ADI or MRL; recommendations on principles and methods in derivation of MRLs, including a new procedure for estimating chronic dietary intakes; the use of a spreadsheet-based procedure for the statistical evaluation of residue depletion data; a revised approach for the derivation of microbiological ADIs; and the Committee's review of and comments on documents provided by the Codex Committee on Residues of Veterinary Drugs. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: three antimicrobial agents (colistin, erythromycin, flumequine), two production aids (melengestrol acetate, ractopamine hydrochloride), an insecticide (trichlorfon (metrifonate)) and an anthelminthic (triclabendazole). In addition, the attempt by the Committee to use tylosin as an example to investigate if evaluations are possible based on published data in the absence of data submissions from sponsors is described. Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes and proposed maximum residue limits. PMID:17373572

  9. Effect In Vitro of Antiparasitic Drugs on Microbial Inhibitor Test Responses for Screening Antibiotic Residues in Goat's Milk.

    PubMed

    Romero, T; Beltrán, M C; Reybroeck, W; Molina, M P

    2015-09-01

    Microbial inhibitor tests are widely used to screen antibiotic residues in milk; however, these tests are nonspecific and may be affected by various substances capable of inhibiting the growth of the test microorganism. The objective of this study was to determine the effect of antiparasitic drugs in goat's milk on the microbial inhibitor test response. Raw antibiotic-free milk from Murciano-Granadina goats was supplemented with eight concentrations of seven antiparasitic substances (albendazole, 10 to 170 mg/kg; closantel, 1 to 140 mg/kg; diclazuril, 8 to 45 mg/kg; febendazole, 10 to 140 mg/kg; levamisole, 40 to 440 mg/kg; diazinon, 8 to 45 mg/kg; and ivermectin, 40 to 200 mg/kg). Twelve replicates for each concentration were analyzed with three microbial inhibitor tests: BRT MRL, Delvotest SP-NT MSC, and Eclipse 100. The results were interpreted visually (negative or positive). Using a logistic regression model, the concentrations of the antiparasitic drugs producing 5% (IC5), 10% (IC10), and 50% (IC50) positive results were determined. In general, the Eclipse 100 test was less sensitive to the effect of antiparasitic substances; the inhibitory concentrations of almost all the drugs assayed were higher than those for other tests. Conversely, the BRT MRL test was most affected, with high levels of interference at lower antiparasitic drug concentrations. Closantel and diazinon interfered with all microbial tests at lower concentrations than did other drugs (IC5 = 1 to 26 and 12 to 20 mg/kg, respectively), and higher concentrations of levamisole and diclazuril (IC5 = 30 to 240 and 50 to 117 mg/kg, respectively) were required to produce 5% positive results. These findings indicate that microbial inhibitor tests can be affected by elevated concentrations of antiparasitic drugs in goat's milk. PMID:26319732

  10. Source discrimination of drug residues in wastewater: The case of salbutamol.

    PubMed

    Depaolini, Andrea Re; Fattore, Elena; Cappelli, Francesca; Pellegrino, Raffaele; Castiglioni, Sara; Zuccato, Ettore; Fanelli, Roberto; Davoli, Enrico

    2016-06-15

    Analytical methods used for pharmaceuticals and drugs of abuse in sewage play a fundamental role in wastewater-based epidemiology (WBE) studies. Here quantitative analysis of drug metabolites in raw wastewaters is used to determine consumption from general population. Its great advantage in public health studies is that it gives objective, real-time data about community use of chemicals, highlighting the relationship between environmental and human health. Within a WBE study on salbutamol use in a large population, we developed a procedure to distinguish human metabolic excretion from external source of contamination, possibly industrial, in wastewaters. Salbutamol is mainly excreted as the sulphate metabolite, which is rapidly hydrolyzed to the parent compound in the environment, so this is currently not detected. When a molecule is either excreted un-metabolized or its metabolites are unstable in the environment, studies can be completed by monitoring the parent compound. In this case it is mandatory to assess whether the drug in wastewater is present because of population use or because of a specific source of contamination, such as industrial manufacturing waste. Because commercial salbutamol mainly occurs as a racemic mixture and is stereoselective in the human metabolism, the enantiomeric relative fraction (EFrel) in wastewater samples should reflect excretion, being unbalanced towards one of two enantiomers, if the drug is of metabolic origin. The procedure described involves chiral analysis of the salbutamol enantiomers by liquid chromatography-tandem mass spectrometry (LC-MS-MS) and calculation of EFrel, to detect samples where external contamination occurs. Samples were collected daily between October and December 2013 from the Milano Nosedo wastewater treatment plant. Carbamazepine and atenolol were measured in the sewage collector, as "control" drugs. Salbutamol EFrel was highly consistent in all samples during this three-month period, but a limited

  11. Understanding Functional Residues of the Cannabinoid CB1 Receptor for Drug Discovery

    PubMed Central

    Shim, Joong-Youn

    2010-01-01

    The brain cannabinoid (CB1) receptor that mediates numerous physiological processes in response to marijuana and other psychoactive compounds is a G protein coupled receptor (GPCR) and shares common structural features with many rhodopsin class GPCRs. For the rational development of therapeutic agents targeting the CB1 receptor, understanding of the ligand-specific CB1 receptor interactions responsible for unique G protein signals is crucial. For a more than a decade, a combination of mutagenesis and computational modeling approaches has been successfully employed to study the ligand-specific CB1 receptor interactions. In this review, after a brief discussion about recent advances in understanding of some structural and functional features of GPCRs commonly applicable to the CB1 receptor, the CB1 receptor functional residues reported from mutational studies are divided into three different types, ligand binding (B), receptor stabilization (S) and receptor activation (A) residues, to delineate the nature of the binding pockets of anandamide, CP55940, WIN55212-2 and SR141716A and to describe the molecular events of the ligand-specific CB1 receptor activation from ligand binding to G protein signaling. Taken these CB1 receptor functional residues, some of which are unique to the CB1 receptor, together with the biophysical knowledge accumulated for the GPCR active state, it is possible to propose the early stages of the CB1 receptor activation process that not only provide some insights into understanding molecular mechanisms of receptor activation but also are applicable for identifying new therapeutic agents by applying the validated structure-based approaches, such as virtual high throughput screening (HTS) and fragment-based approach (FBA). PMID:20370713

  12. Toxin acidic residue evolutionary function-guided design of de novo peptide drugs for the immunotherapeutic target, the Kv1.3 channel

    PubMed Central

    Chen, Zongyun; Hu, Youtian; Hong, Jing; Hu, Jun; Yang, Weishan; Xiang, Fang; Yang, Fan; Xie, Zili; Cao, Zhijian; Li, Wenxin; Lin, Donghai; Wu, Yingliang

    2015-01-01

    During the long-term evolution of animal toxins acting on potassium channels, the acidic residues can orientate the toxin binding interfaces by adjusting the molecular polarity. Based on the evolutionary function of toxin acidic residues, de novo peptide drugs with distinct binding interfaces were designed for the immunotherapeutic target, the Kv1.3 channel. Using a natural basic toxin, BmKTX, as a template, which contains 2 acidic residues (Asp19 and Asp33), we engineered two new peptides BmKTX-19 with 1 acidic residue (Asp33), and BmKTX-196 with 2 acidic residues (Asp6 and Asp33) through only adjusting acidic residue distribution for reorientation of BmKTX binding interface. Pharmacological experiments indicated that BmKTX-19 and BmKTX-196 peptides were specific inhibitors of the Kv1.3 channel and effectively suppressed cytokine secretion. In addition to the structural similarity between the designed and native peptides, both experimental alanine-scanning mutagenesis and computational simulation further indicated that the binding interface of wild-type BmKTX was successfully reoriented in BmKTX-19 and BmKTX-196, which adopted distinct toxin surfaces as binding interfaces. Together, these findings indicate not only the promising prospect of BmKTX-19 and BmKTX-196 as drug candidates but also the desirable feasibility of the evolution-guided peptide drug design for discovering numerous peptide drugs for the Kv1.3 channel. PMID:25955787

  13. Computational Biology Tools for Identifying Specific Ligand Binding Residues for Novel Agrochemical and Drug Design.

    PubMed

    Neshich, Izabella Agostinho Pena; Nishimura, Leticia; de Moraes, Fabio Rogerio; Salim, Jose Augusto; Villalta-Romero, Fabian; Borro, Luiz; Yano, Inacio Henrique; Mazoni, Ivan; Tasic, Ljubica; Jardine, Jose Gilberto; Neshich, Goran

    2015-01-01

    The term "agrochemicals" is used in its generic form to represent a spectrum of pesticides, such as insecticides, fungicides or bactericides. They contain active components designed for optimized pest management and control, therefore allowing for economically sound and labor efficient agricultural production. A "drug" on the other side is a term that is used for compounds designed for controlling human diseases. Although drugs are subjected to much more severe testing and regulation procedures before reaching the market, they might contain exactly the same active ingredient as certain agrochemicals, what is the case described in present work, showing how a small chemical compound might be used to control pathogenicity of Gram negative bacteria Xylella fastidiosa which devastates citrus plantations, as well as for control of, for example, meningitis in humans. It is also clear that so far the production of new agrochemicals is not benefiting as much from the in silico new chemical compound identification/discovery as pharmaceutical production. Rational drug design crucially depends on detailed knowledge of structural information about the receptor (target protein) and the ligand (drug/agrochemical). The interaction between the two molecules is the subject of analysis that aims to understand relationship between structure and function, mainly deciphering some fundamental elements of the nanoenvironment where the interaction occurs. In this work we will emphasize the role of understanding nanoenvironmental factors that guide recognition and interaction of target protein and its function modifier, an agrochemical or a drug. The repertoire of nanoenvironment descriptors is used for two selected and specific cases we have approached in order to offer a technological solution for some very important problems that needs special attention in agriculture: elimination of pathogenicity of a bacterium which is attacking citrus plants and formulation of a new fungicide. Finally

  14. Assessment of MEKC suitability for residue drug monitoring on pharmaceutical manufacturing equipment.

    PubMed

    Boca, Madalina Brindusa; Pretorius, Etheresia; Kgaje, Christopher; Apostolides, Zeno

    2008-03-13

    The suitability of micellar electrokinetic chromatography for the simultaneous trace determination of several compounds (sulfamethoxazole, trimethoprim, sulfanilic acid, sulfanilamide, 3,4,5-trimethoxybenzoic acid and nonoxynol-9) was assessed. The mixture was separated within 14min at an applied voltage of 22kV by using 30mM phosphate electrolyte, containing 10mM SDS, adjusted to pH 7.8. Under optimized separation conditions acceptable levels of linearity, precision and accuracy were obtained for all compounds. The method could be used as part of a cleaning validation study when assaying trace levels of co-trimoxazole drug, some of its decomposition products and detergent in the swab samples collected from pharmaceutical manufacturing equipment, after cleaning. PMID:18178359

  15. Analysis of veterinary drug residues in cheese by ultra-high-performance LC coupled to triple quadrupole MS/MS.

    PubMed

    Gómez Pérez, María Luz; Romero-González, Roberto; Martínez Vidal, José Luis; Garrido Frenich, Antonia

    2013-04-01

    A simple, reliable, and fast multiresidue method has been developed for the determination of 17 veterinary drugs belonging to several families (macrolides, sulfonamides, and anthelmintics) in cheese at trace levels. Ultra-high-performance LC coupled to MS/MS has been used for the analysis of these compounds in less than 9 min. Veterinary drug residues have been extracted from cheese samples using a QuEChERS (quick, easy, cheap, effective, rugged, and safe)-based extraction procedure without applying any further clean-up step. Matrix-matched calibration was used for quantification and recoveries were calculated at three concentration levels (10, 50, and 100 μg/kg). The obtained values ranged from 70 to 110% for the selected compounds except for tylosin and josamycin at 100 μg/kg (111.7 and 112.7%, respectively). Intra- and interday precision were also evaluated and RSDs were lower than 25% in all the cases. LOQs ranged from 0.3 μg/kg (for thiabendazole, oxfendazole, mebendazole, josamycin, and fenbendazole) to 10.5 μg/kg (abamectin), whereas decision limit and detection capability ranged from 2.3 (thiabendazole) to 11.3 (abamectin) and 4.2 (thiabendazole) to 14.3 μg/kg (abamectin), respectively. Finally, 13 samples were analyzed and traces of thiabendazole were detected in two different cheeses. PMID:23576365

  16. Veterinary Drugs and Growth Promoters Residues in Meat and Processed Meats

    NASA Astrophysics Data System (ADS)

    Reig, Milagro; Toldrá, Fidel

    Veterinary drugs, which comprise a large number of different types of substances, are generally intended for therapeutic (to control infectious diseases) and prophylactic (to prevent against infections) purposes in farm animals. Other substances with growth promoting effect may exert antimicrobial effect against the microbial flora in the gut to take maximum profit of nutrients in the feed or by affecting the animal’s metabolism. Most of these substances are orally active and can be administered either in the feed or in the drinking water. Other active hormones are applied in the form of small implants into the subcutaneous tissue of the ears. These are slow release (several weeks or months) devices and the ears are discarded at the slaughter. Growth promoters allow a better efficiency in the feed conversion rate. The net effect is an increased protein deposition, partly due to muscle proteases inhibition (Fiems, Buts, Boucque, Demeyer, & Cottyn, 1990), usually linked to fat utilization (Brockman & Laarveld, 1986). The result is a leaner meat (Lone, 1997) with some toughness derived from the production of connective tissue and collagen crosslinking (Miller, Judge, Diekman, Hudgens, & Aberle, 1989; Miller, Judge, & Schanbacher, 1990). Some recent fraudulent practices, consisting of the use of a kind of “cocktails” or mixtures of several substances like β-agonists and corticosteroids at very low amounts (Monsón et al., 2007), are difficult to detect with modern analytical instrumentation. They try to obtain a synergistic effect for a similar growth promotion with lower probability of detection by official control laboratories (Reig & Toldrá, 2007).

  17. Analysis of veterinary drug residues in shrimp: a multi-class method by liquid chromatography-quadrupole ion trap mass spectrometry.

    PubMed

    Li, Hui; Kijak, Philip James; Turnipseed, Sherri B; Cui, Wei

    2006-05-19

    A liquid chromatography-mass spectrometry (LC-MS) method was developed to screen and confirm veterinary drug residues in raw shrimp meat. This method simultaneously monitors 18 drugs of different classes, including oxytetracycline (OTC), sulfonamides, quinolones, cationic dyes, and toltrazuril sulfone (TOLS). The homogenized shrimp meat is extracted with 5% trichloroacetic acid. The extract is further cleaned using polymer-based SPE. A 50 mm phenyl column separates the analytes, prior to analysis with an ion trap mass spectrometer interfaced with an atmospheric pressure chemical ionization source. This method is able to confirm oxytetracycline residues at 200 ng/g, toltrazuril sulfone at 50 ng/g, sulfaquinoxaline at 20 ng/g, and the other 15 drugs at 10 ng/g or lower levels. An estimate of the level of residues can also be made so that only confirmed samples above action levels will be sent for quantitation. The method is validated with both fortified and incurred samples, using multiple shrimp species as well. This multi-class method can provide a means to simultaneously monitor for a wide range of illegal drug residues in shrimp. PMID:16597519

  18. Structural characterization of fragment ions by electrospray ionization and Q-TOF mass spectrometry to support regulatory analysis of veterinary drug residues in foods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    RATIONALE: Monitoring of veterinary drug residues in foods is often conducted using liquid chromatography – tandem mass spectrometry (LC-MS/MS). Results have high economic stakes for producers, but the ions monitored are usually selected due to signal intensities without structural interpretation. ...

  19. Ruggedness testing and validation of a practical analytical method for > 100 veterinary drug residues in bovine muscle by ultrahigh performance liquid chromatography – tandem mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, optimization, extension, and validation of a streamlined, qualitative and quantitative multiclass, multiresidue method was conducted to monitor great than100 veterinary drug residues in meat using ultrahigh-performance liquid chromatography – tandem mass spectrometry (UHPLC-MS/MS). I...

  20. The effect of administering long-acting oxytetracycline and tilmicosin either by dart gun or by hand on injection site lesions and drug residues in beef cattle.

    PubMed Central

    Van Donkersgoed, J; VanderKop, M; Salisbury, C; Sears, L; Holowath, J

    1999-01-01

    Forty yearling cattle were injected intramuscularly with long-acting oxytetracycline and subcutaneously with tilmicosin by dart gun or by hand in a chute 28 days prior to slaughter. The drugs caused injection site lesions and antibiotic residues in the neck and thigh that varied by technique, dose, and site. PMID:12001341

  1. An update discussion on the current assessment of the safety of veterinary antimicrobial drug residues in food with regard to their impact on the human intestinal microbiome.

    PubMed

    Cerniglia, Carl E; Pineiro, Silvia A; Kotarski, Susan F

    2016-05-01

    The human gastrointestinal tract ecosystem consists of complex and diverse microbial communities that have now been collectively termed the intestinal microbiome. Recent scientific breakthroughs and research endeavours have increased our understanding of the important role the intestinal microbiome plays in human health and disease. The use of antimicrobial new animal drugs in food-producing animals may result in the presence of low levels of drug residues in edible foodstuffs. There is concern that antimicrobial new animal drugs in or on animal-derived food products at residue-level concentrations could disrupt the colonization barrier and/or modify the antimicrobial resistance profile of human intestinal bacteria. Therapeutic doses of antimicrobial drugs have been shown to promote shifts in the intestinal microbiome, and these disruptions promote the emergence of antimicrobial-resistant bacteria. To assess the effects of antimicrobial new animal drug residues in food on human intestinal bacteria, many national regulatory agencies and international committees follow a harmonized process, VICH GL36(R), which was issued by a trilateral organization of the European Union, the USA, and Japan called the International Cooperation on Harmonization of Technical Requirements for Veterinary Medicinal Products (VICH). The guidance describes a general approach currently used by national regulatory agencies and international committees to assess the effects of antimicrobial new animal drug residues in animal-derived food on human intestinal bacteria. The purpose of this review is to provide an overview of this current approach as part of the antimicrobial new animal drug approval process in participating countries, give insights on the microbiological endpoints used in this safety evaluation, and discuss the availability of new information. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27443209

  2. Hepatotoxicity of Pentavalent Antimonial Drug: Possible Role of Residual Sb(III) and Protective Effect of Ascorbic Acid

    PubMed Central

    Kato, Kelly C.; Morais-Teixeira, Eliane; Reis, Priscila G.; Silva-Barcellos, Neila M.; Salaün, Pascal; Campos, Paula P.; Dias Corrêa-Junior, José; Rabello, Ana; Demicheli, Cynthia

    2014-01-01

    Pentavalent antimonial drugs such as meglumine antimoniate (Glucantime [Glu; Sanofi-Aventis, São Paulo, Brazil]) produce severe side effects, including cardiotoxicity and hepatotoxicity, during the treatment of leishmaniasis. We evaluated the role of residual Sb(III) in the hepatotoxicity of meglumine antimoniate, as well as the protective effect of the antioxidant ascorbic acid (AA) during antimonial chemotherapy in a murine model of visceral leishmaniasis. BALB/c mice infected with Leishmania infantum were treated intraperitoneally at 80 mg of Sb/kg/day with commercial meglumine antimoniate (Glu) or a synthetic meglumine antimoniate with lower Sb(III) level (MA), in association or not with AA (15 mg/kg/day), for a 20-day period. Control groups received saline or saline plus AA. Livers were evaluated for hepatocytes histological alterations, peroxidase activity, and apoptosis. Increased proportions of swollen and apoptotic hepatocytes were observed in animals treated with Glu compared to animals treated with saline or MA. The peroxidase activity was also enhanced in the liver of animals that received Glu. Cotreatment with AA reduced the extent of histological changes, the apoptotic index, and the peroxidase activity to levels corresponding to the control group. Moreover, the association with AA did not affect the hepatic uptake of Sb and the ability of Glu to reduce the liver and spleen parasite loads in infected mice. In conclusion, our data supports the use of pentavalent antimonials with low residue of Sb(III) and the association of pentavalent antimonials with AA, as effective strategies to reduce side effects in antimonial therapy. PMID:24189251

  3. Pore-exposed tyrosine residues of P-glycoprotein are important hydrogen-bonding partners for drugs.

    PubMed

    Dönmez Cakil, Yaprak; Khunweeraphong, Narakorn; Parveen, Zahida; Schmid, Diethart; Artaker, Matthias; Ecker, Gerhard F; Sitte, Harald H; Pusch, Oliver; Stockner, Thomas; Chiba, Peter

    2014-03-01

    The multispecific efflux transporter, P-glycoprotein, plays an important role in drug disposition. Substrate translocation occurs along the interface of its transmembrane domains. The rotational C2 symmetry of ATP-binding cassette transporters implies the existence of two symmetry-related sets of substrate-interacting amino acids. These sets are identical in homodimeric transporters, and remain evolutionary related in full transporters, such as P-glycoprotein, in which substrates bind preferentially, but nonexclusively, to one of two binding sites. We explored the role of pore-exposed tyrosines for hydrogen-bonding interactions with propafenone type ligands in their preferred binding site 2. Tyrosine 953 is shown to form hydrogen bonds not only with propafenone analogs, but also with the preferred site 1 substrate rhodamine123. Furthermore, an accessory role of tyrosine 950 for binding of selected propafenone analogs is demonstrated. The present study demonstrates the importance of domain interface tyrosine residues for interaction of small molecules with P-glycoprotein. PMID:24366667

  4. Short communication: Drug residues in goat milk after prophylactic use of antibiotics in intravaginal sponges for estrus synchronization.

    PubMed

    Romero, T; Balado, J; Althaus, R L; Beltrán, M C; Molina, M P

    2016-01-01

    The aim of this study was to determine whether the prophylactic use of antibiotics in intravaginal sponges used for estrus synchronization in goats may result in the presence of inhibitors in milk and, therefore, of positive results by microbial screening tests. Ninety-eight Murciano-Granadina goats were used, divided into 7 groups of 14 animals. Intravaginal sponges were placed in 6 groups using 2 concentrations of 3 different antibiotics: doxycycline, oxytetracycline, and sulfathiazole-framycetin. The sponges of the control group were placed without antibiotics. Milk samples were collected daily until 7 d posttreatment and analyzed using 3 microbial tests. Positive samples were retested by specific receptor-binding assays to confirm the positive results. Vaginal status was evaluated by visual assessment of the external aspect of the sponges after removal. The microbial test response was not affected by either day posttreatment or dose of antibiotic used, except for oxytetracycline at the higher concentration. Moreover, no positive results were obtained using receptor-binding assays, suggesting that residues, if present in milk, did not exceed the regulatory (safety) levels established for these drugs. The occurrence of soiled sponges was higher in the control group. With respect to the dose of antibiotics used, no significant differences were found for the lower dose administered. However, a significant increase in the percentage of clean sponges was observed for the higher dose of doxycycline. We conclude that the prophylactic use of low doses of doxycycline, oxytetracycline, or sulfathiazole in intravaginal sponges used for synchronization of estrus helps to reduce clinical vaginitis in dairy goats and does not seem to be the cause of positive results in microbial inhibitor tests used to detect antibiotics in goat milk. PMID:26585470

  5. Determination of small halogenated carboxylic acid residues in drug substances by high performance liquid chromatography-diode array detection following derivatization with nitro-substituted phenylhydrazines.

    PubMed

    Hou, Desheng; Fan, Jingjing; Han, Lingfei; Ruan, Xiaoling; Feng, Feng; Liu, Wenyuan; Zheng, Feng

    2016-03-18

    A method for the determination of small halogenated carboxylic acid (HCA) residues in drug substances is urgently needed because of the potential of HCAs for genotoxicity and carcinogenicity in humans. We have now developed a simple method, involving derivatization followed by high performance liquid chromatography-diode array detection (HPLC-DAD), for the determination of six likely residual HCAs (monochloroacetic acid, monobromoacetic acid, dichloroacetic acid, 2-chloropropionic acid, 2-bromopropionic acid and 3-chloropropionic acid) in drug substances. Different nitro-substituted phenylhydrazines (NPHs) derivatization reagents were systematically compared and evaluated. 2-Nitrophenylhydrazine hydrochloride (2-NPH·HCl) was selected as the most suitable choice since its derivatives absorb strongly at 392 nm, a region of the spectrum where most drug substances and impurities absorb very weakly. During the derivatization process, the commonly used catalyst, pyridine, caused rapid dechlorination or chlorine substitution of α-halogenated derivatives. To avoid these unwanted side reactions, a reliable derivatization method that did not use pyridine was developed. Reaction with 2-NPH·HCl using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride as coupling agent in acetonitrile-water (70:30) at room temperature for 2h gave complete reaction and avoided degradation products. The derivatives were analyzed, without any pretreatment, using gradient HPLC with detection in the near visible region. Organic acids commonly found in drug substances and other impurities did not interfere with the analysis. Good linearity (r>0.999) and low limits of quantitation (0.05-0.12 μg mL(-1)) were obtained. The mean recoveries were in the range of 80-115% with RSD <5.81% except for 3-CPA in ibuprofen which was 78.5%. The intra- and inter-day precisions were expressed as RSD <1.98% and <4.39%, respectively. Finally, the proposed method was successfully used for the residue

  6. Development and Validation of a Multiclass Method for Analysis of Veterinary Drug Residues in Milk Using Ultrahigh Performance Liquid Chromatography Electrospray Ionization Quadrupole Orbitrap Mass Spectrometry.

    PubMed

    Wang, Jian; Leung, Daniel; Chow, Willis; Chang, James; Wong, Jon W

    2015-10-21

    This paper presents the development and validation of a multiclass method for the analysis of veterinary drug residues in milk using ultrahigh performance liquid chromatography electrospray ionization quadrupole Orbitrap mass spectrometry (UHPLC/ESI Q-Orbitrap). The 12 classes of veterinary drugs (a total of 125) included in this study were endectocides, fluoroquinolones, ionophores, macrolides, nitroimidazole, NSAIDs, β-lactams, penicillins, phenicols, sulfonamides, tetracyclines, and aminoglycosides. Veterinary drug residues in milk were extracted using a modified salting-out supported liquid extraction (SOSLE) method, which entailed the precipitation of milk proteins using an extraction buffer (oxalic acid and EDTA, pH 3) and acetonitrile, a salting-out acetonitrile/water phase separation using ammonium sulfate, and solid-phase extraction (SPE) using polymeric reversed-phase sorbent cartridges. The final extracts were concentrated and reconstituted into a buffer solution and analyzed using UHPLC/ESI Q-Orbitrap mass spectrometry. The developed method was validated using a nested experimental design to evaluate the method performance characteristics, such as overall recovery, intermediate precision, and measurement uncertainty. The method was able to quantify or screen up to 105 veterinary drugs from 11 different classes, except aminoglycosides. The limits of quantification were as low as 1.0 μg/kg, with an analytical range from 1.0 to 100.0 μg/kg in milk. PMID:26416602

  7. A sensitive and semi-quantitative method for determination of multi-drug residues in animal body fluids using multiplex dipstick immunoassay.

    PubMed

    Han, Shuaijuan; Zhou, Tianjiao; Yin, Bingjie; He, Pingli

    2016-07-13

    The objective of this research was to develop a multiplex dipstick immunoassay method for the simultaneous determination of multi-veterinary drug residues, such as β-agonists, sulfonamides, and tetracyclines in milk, urine, and serum. The multiplex dipstick assay format was based on an indirect competitive approach: Three test lines (different antigens) and one control line (goat anti-mouse IgG) were located on the strip membrane. Labeled antibodies were freeze-dried in microwells. Samples did not require pretreatment and could be directly analyzed within 10 min. Threshold levels in different sample matrices were visually estimated at 0.3-0.45 ng mL(-1) for clenbuterol; 3-4 ng mL(-1) for sulfadiazine; and 4.5-6 ng mL(-1) for tetracycline, respectively. The linear relationship between the concentrations of veterinary drug residues and the Au nanoparticles plasmon absorbance allowed quantitative determination of these veterinary drug residues. The recoveries of clenbuterol, sulfadiazine and tetracycline in spiked samples ranged from 78.4% to 112.6%, and the relative standard deviations were below 11.2%. Analysis of animal samples suggested that the proposed multiplex dipstick assay method was consistent with the LC-MS/MS method. The percentage of false results was less than or equal to 5%. Thus, the proposed multiplex dipstick assay is inexpensive, easy-to-use, and suitable for the purposes of rapid and comprehensive screening of 3 families of β-agonists, sulfonamides and tetracyclines including 26 drugs in animal body fluids. PMID:27237838

  8. Analysis of Veterinary Drug and Pesticide Residues Using the Ethyl Acetate Multiclass/Multiresidue Method in Milk by Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Imamoglu, Husniye; Oktem Olgun, Elmas

    2016-01-01

    A rapid and simple multiclass, ethyl acetate (EtOAc) multiresidue method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) detection was developed for the determination and quantification of 26 veterinary drugs and 187 total pesticide residues in milk. Sample preparation was a simple procedure based on liquid-liquid extraction with ethyl acetate containing 0.1% acetic acid, followed by centrifugation and evaporation of the supernatant. The residue was dissolved in ethyl acetate with 0.1% acetic acid and centrifuged prior to LC-MS/MS analysis. Chromatographic separation of analytes was performed on an Inertsil X-Terra C18 column with acetic acid in methanol and water gradient. The repeatability and reproducibility were in the range of 2 to 13% and 6 to 16%, respectively. The average recoveries ranged from 75 to 120% with the RSD (n = 18). The developed method was validated according to the criteria set in Commission Decision 2002/657/EC and SANTE/11945/2015. The validated methodology represents a fast and cheap alternative for the simultaneous analysis of veterinary drug and pesticide residues which can be easily extended to other compounds and matrices. PMID:27293962

  9. Determination of anthelmintic drug residues in milk using ultra high performance liquid chromatography-tandem mass spectrometry with rapid polarity switching.

    PubMed

    Whelan, Michelle; Kinsella, Brian; Furey, Ambrose; Moloney, Mary; Cantwell, Helen; Lehotay, Steven J; Danaher, Martin

    2010-07-01

    A new UHPLC-MS/MS (ultra high performance liquid chromatography coupled to tandem mass spectrometry) method was developed and validated to detect 38 anthelmintic drug residues, consisting of benzimidazoles, avermectins and flukicides. A modified QuEChERS-type extraction method was developed with an added concentration step to detect most of the analytes at <1 microg kg(-1) levels in milk. Anthelmintic residues were extracted into acetonitrile using magnesium sulphate and sodium chloride to induce liquid-liquid partitioning followed by dispersive solid phase extraction for cleanup. The extract was concentrated into dimethyl sulphoxide, which was used as a keeper to ensure analytes remain in solution. Using rapid polarity switching in electrospray ionisation, a single injection was capable of detecting both positively and negatively charged ions in a 13 min run time. The method was validated at two levels: the unapproved use level and at the maximum residue level (MRL) according to Commission Decision (CD) 2002/657/EC criteria. The decision limit (CCalpha) of the method was in the range of 0.14-1.9 and 11-123 microg kg(-1) for drugs validated at unapproved and MRL levels, respectively. The performance of the method was successfully verified for benzimidazoles and levamisole by participating in a proficiency study. PMID:20564781

  10. Analytical method for fast screening and confirmation of multi-class veterinary drug residues in fish and shrimp by LC-MS/MS.

    PubMed

    Kim, Junghyun; Suh, Joon Hyuk; Cho, Hyun-Deok; Kang, Wonjae; Choi, Yong Seok; Han, Sang Beom

    2016-01-01

    A multi-class, multi-residue analytical method based on LC-MS/MS detection was developed for the screening and confirmation of 28 veterinary drug and metabolite residues in flatfish, shrimp and eel. The chosen veterinary drugs are prohibited or unauthorised compounds in Korea, which were categorised into various chemical classes including nitroimidazoles, benzimidazoles, sulfones, quinolones, macrolides, phenothiazines, pyrethroids and others. To achieve fast and simultaneous extraction of various analytes, a simple and generic liquid extraction procedure using EDTA-ammonium acetate buffer and acetonitrile, without further clean-up steps, was applied to sample preparation. The final extracts were analysed by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The method was validated for each compound in each matrix at three different concentrations (5, 10 and 20 ng g(-1)) in accordance with Codex guidelines (CAC/GL 71-2009). For most compounds, the recoveries were in the range of 60-110%, and precision, expressed as the relative standard deviation (RSD), was in the range of 5-15%. The detection capabilities (CCβs) were below or equal to 5 ng g(-1), which indicates that the developed method is sufficient to detect illegal fishery products containing the target compounds above the residue limit (10 ng g(-1)) of the new regulatory system (Positive List System - PLS). PMID:26751111

  11. Analysis of Veterinary Drug and Pesticide Residues Using the Ethyl Acetate Multiclass/Multiresidue Method in Milk by Liquid Chromatography-Tandem Mass Spectrometry

    PubMed Central

    Imamoglu, Husniye; Oktem Olgun, Elmas

    2016-01-01

    A rapid and simple multiclass, ethyl acetate (EtOAc) multiresidue method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) detection was developed for the determination and quantification of 26 veterinary drugs and 187 total pesticide residues in milk. Sample preparation was a simple procedure based on liquid–liquid extraction with ethyl acetate containing 0.1% acetic acid, followed by centrifugation and evaporation of the supernatant. The residue was dissolved in ethyl acetate with 0.1% acetic acid and centrifuged prior to LC-MS/MS analysis. Chromatographic separation of analytes was performed on an Inertsil X-Terra C18 column with acetic acid in methanol and water gradient. The repeatability and reproducibility were in the range of 2 to 13% and 6 to 16%, respectively. The average recoveries ranged from 75 to 120% with the RSD (n = 18). The developed method was validated according to the criteria set in Commission Decision 2002/657/EC and SANTE/11945/2015. The validated methodology represents a fast and cheap alternative for the simultaneous analysis of veterinary drug and pesticide residues which can be easily extended to other compounds and matrices. PMID:27293962

  12. Structural characterization of product ions by electrospray ionization and quadrupole time-of-flight mass spectrometry to support regulatory analysis of veterinary drug residues in foods Part 2: Benzimidazoles nitromidaz.....

    Technology Transfer Automated Retrieval System (TEKTRAN)

    RATIONALE: Analysis for identification and quantification of regulated veterinary drug residues in foods are usually achieved by liquid chromatography coupled to tandem mass spectrometry. The instrument method requires the selection of characteristic ions, but structure elucidation is seldom perform...

  13. Simultaneous determination of multiveterinary drug residues in pork meat by liquid chromatography-tandem mass spectrometry combined with solid phase extraction.

    PubMed

    Xie, Wen; Han, Chao; Hou, Jianbo; Wang, Feng; Qian, Yan; Xi, Junyang

    2012-12-01

    An LC-MS/MS method developed for simultaneous analysis of 54 veterinary drug residues of six families in pork meat samples, including sulfanilamide, nitroimidazoles, quinolones, macrolide antibiotics, lincosamides, and praziquantel. The pork meat sample was prepared by extraction with ACN, and clean-up on a C(18) SPE cartridge. The sample was separated on a C(8) column and eluted with ACN, methanol, and formic acid. The MS/MS detector is operated in the multiple reaction monitoring mode, acquiring two specific precursor-product ion transitions per target compound. The method showed excellent linearity (R(2) ≥ 0.99) and high precision (relative SD, RSD ≤ 19.8%) for all compounds. The method quantification limits of 54 veterinary drug residues were in the range of 0.3-3.0 μg/kg. Recoveries for most analytes based on matrix-matched calibration in matrices were 20.9-121.0%. This method has been successfully applied for analysis of more than 100 pork meat samples from the local market; five of the 54 drugs were detected. PMID:23225712

  14. Multi-residue method for the detection of veterinary drugs in distillers grains by liquid chromatography-Orbitrap high resolution mass spectrometry.

    PubMed

    Kaklamanos, George; Vincent, Ursula; von Holst, Christoph

    2013-12-27

    Distillers Grain (DG) is an important by-product of ethanol production. The ethanol production process uses only the starch portion of the plant and all the remaining nutrients, protein, fat, minerals, and vitamins remain in DGs, a valuable feed material for livestock. The use of antimicrobial drugs is helpful to limit harmful bacterial growth during the early part of the fermentation process. This can lead to the possible presence of contaminants in the by-products that are used in the food and feed industries, resulting in a major concern for the development of bacterial resistance in both humans and animals. To facilitate the detection of antimicrobial and other commonly used veterinary drugs in DGs, a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed targeting a wide range of 12 chemical classes of anti-bacterial substances and drugs, such as ionophore and non-ionophore authorized coccidiostats, banned coccidiostats, macrolides, tetracyclines, nitroimidazoles, amphenicols, quinolones, sulphonamides, tranquilizers, non-steroidal anti-inflammatory drugs and benzimidazoles. Following a simple and fast extraction step with a mixture of organic solvents, the extract was directly injected into the LC coupled to an Orbitrap mass analyzer. The identification of residues is based on accurate mass measurement. The high mass resolution of 50,000 full width at half maximum (FWHM) and corresponding narrow mass windows permitted a very selective and sensitive detection of the analytes in such a complex matrix. A single-laboratory validation procedure was carried out evaluating selectivity, sensitivity, linearity, precision and accuracy. The method showed satisfactory analytical performance for precision and trueness, and allowed the determination of the compounds at low concentration. The proposed multi-method demonstrated that liquid chromatography coupled to an Orbitrap mass spectrometer is a promising analytical technique, suitable for

  15. Per-residue energy decomposition pharmacophore model to enhance virtual screening in drug discovery: a study for identification of reverse transcriptase inhibitors as potential anti-HIV agents

    PubMed Central

    Cele, Favourite N; Ramesh, Muthusamy; Soliman, Mahmoud ES

    2016-01-01

    A novel virtual screening approach is implemented herein, which is a further improvement of our previously published “target-bound pharmacophore modeling approach”. The generated pharmacophore library is based only on highly contributing amino acid residues, instead of arbitrary pharmacophores, which are most commonly used in the conventional approaches in literature. Highly contributing amino acid residues were distinguished based on free binding energy contributions obtained from calculation from molecular dynamic (MD) simulations. To the best of our knowledge; this is the first attempt in the literature using such an approach; previous approaches have relied on the docking score to generate energy-based pharmacophore models. However, docking scores are reportedly unreliable. Thus, we present a model for a per-residue energy decomposition, constructed from MD simulation ensembles generating a more trustworthy pharmacophore model, which can be applied in drug discovery workflow. This work is aimed at introducing a more rational approach to the field of drug design, rather than comparing the validity of this approach against those previously reported. We recommend additional computational and experimental work to further validate this approach. This approach was used to screen for potential reverse transcriptase inhibitors using the pharmacophoric features of compound GSK952. The complex was subjected to docking, thereafter, MD simulation confirmed the stability of the system. Experimentally determined inhibitors with known HIV-reverse transcriptase inhibitory activity were used to validate the protocol. Two potential hits (ZINC46849657 and ZINC54359621) showed a significant potential with regard to free binding energy. Reported results obtained from this work confirm that this new approach is favorable in the future of the drug design industry. PMID:27114700

  16. Per-residue energy decomposition pharmacophore model to enhance virtual screening in drug discovery: a study for identification of reverse transcriptase inhibitors as potential anti-HIV agents.

    PubMed

    Cele, Favourite N; Ramesh, Muthusamy; Soliman, Mahmoud Es

    2016-01-01

    A novel virtual screening approach is implemented herein, which is a further improvement of our previously published "target-bound pharmacophore modeling approach". The generated pharmacophore library is based only on highly contributing amino acid residues, instead of arbitrary pharmacophores, which are most commonly used in the conventional approaches in literature. Highly contributing amino acid residues were distinguished based on free binding energy contributions obtained from calculation from molecular dynamic (MD) simulations. To the best of our knowledge; this is the first attempt in the literature using such an approach; previous approaches have relied on the docking score to generate energy-based pharmacophore models. However, docking scores are reportedly unreliable. Thus, we present a model for a per-residue energy decomposition, constructed from MD simulation ensembles generating a more trustworthy pharmacophore model, which can be applied in drug discovery workflow. This work is aimed at introducing a more rational approach to the field of drug design, rather than comparing the validity of this approach against those previously reported. We recommend additional computational and experimental work to further validate this approach. This approach was used to screen for potential reverse transcriptase inhibitors using the pharmacophoric features of compound GSK952. The complex was subjected to docking, thereafter, MD simulation confirmed the stability of the system. Experimentally determined inhibitors with known HIV-reverse transcriptase inhibitory activity were used to validate the protocol. Two potential hits (ZINC46849657 and ZINC54359621) showed a significant potential with regard to free binding energy. Reported results obtained from this work confirm that this new approach is favorable in the future of the drug design industry. PMID:27114700

  17. Prediction of the residue levels of drugs in eggs, using physicochemical properties and their influence on passive diffusion processes.

    PubMed

    Schefferlie, G J; Hekman, P

    2016-08-01

    Based on a physiologically based pharmacokinetic model, describing the relationship between the plasma concentration of a drug and its deposition into eggs, general transport constants into yolk and albumen were derived, for a number of compounds, using experimental data from literature. Using only generally accepted concepts in passive diffusion theory, these transport constants were used to derive and calibrate general equations, describing the transport into yolk and albumen, in terms of the physicochemical properties of a drug. It is shown that, in theory, it is possible to calculate/predict the transport constants, using the physicochemical parameters: pKa and plasma protein binding. For a number of sulfonamides, the model was used to predict their distribution between egg yolk and albumen; the outcome was compared to data found in literature. Within this dataset, the lipophilic nature of a drug does not seem to play a major role in explaining the distribution ratio of a drug between albumen and yolk. PMID:26763131

  18. Development of fast screening methods for the analysis of veterinary drug residues in milk by liquid chromatography-triple quadrupole mass spectrometry.

    PubMed

    Martínez Vidal, José Luis; Garrido Frenich, Antonia; Aguilera-Luiz, María M; Romero-González, Roberto

    2010-08-01

    Two rapid multi-residue screening methods for the determination of 21 veterinary drugs in milk by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) have been developed and compared. For both methods, veterinary drugs were extracted from milk samples using a rapid extraction procedure based on the modification of the well-known QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method, and no further clean-up steps were necessary. One screening method was based on the selection of a characteristic neutral loss or product ion of the various families of compounds, whereas another one was based on the choice of a selected reaction monitoring (SRM) for each compound. These methods were compared with regards to false negatives, cut-off values and the unreliability region. The total run time for both methods was 3 min, allowing quick selection of samples that contained veterinary drugs. Non-negative samples were re-analyzed by the UHPLC-MS/MS confirmation/quantification method, which consisted in the monitoring of two SRM for each compound. The methods were validated according to international guides. The proposed analytical methods allow for the identification and confirmation of the target veterinary drugs at trace levels employing quick analysis time. PMID:20101501

  19. Molecularly imprinted solid-phase extraction for the determination of ten macrolide drugs residues in animal muscles by liquid chromatography-tandem mass spectrometry.

    PubMed

    Song, Xuqin; Zhou, Tong; Liu, Qingying; Zhang, Meiyu; Meng, Chenying; Li, Jiufeng; He, Limin

    2016-10-01

    A simple and sensitive method based on molecularly imprinted solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry was developed for the determination of the residues of ten macrolide drugs in swine, cattle and chicken muscles samples. The molecularly imprinted polymers (MIPs) were synthesized using tylosin as a template and methacrylic acid as a functional monomer. Samples were extracted with sodium borate buffer solution and ethyl acetate, and purified by the MIP cartridge. The results showed that the cartridge exhibited good recognition performance for macrolides, and better purification effect than the traditional solid-phase extraction cartridges. Recoveries of analytes at three spiking levels 1, 5 and 20μgkg(-1) ranged from 60.7% to 100.3% with the relative standard deviations less than 14%. The limits of detection of the method were between 0.1 and 0.4μgkg(-1). The method is useful for the routine monitoring of the residues of macrolide drugs in animal muscles. PMID:27132837

  20. Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development

    PubMed Central

    Liu, Chia-Lin; Hung, Hui-Chen; Lo, Shou-Chen; Chiang, Ching-Hui; Chen, I-Jung; Hsu, John T.-A.; Hou, Ming-Hon

    2016-01-01

    Nucleoprotein (NP) is the most abundant type of RNA-binding viral protein in influenza A virus–infected cells and is necessary for viral RNA transcription and replication. Recent studies demonstrated that influenza NP is a valid target for antiviral drug development. The surface of the groove, covered with numerous conserved residues between the head and body domains of influenza A NP, plays a crucial role in RNA binding. To explore the mechanism by which NP binds RNA, we performed a series of site-directed mutagenesis in the RNA-binding groove, followed by surface plasmon resonance (SPR), to characterize the interactions between RNA and NP. Furthermore, a role of Y148 in NP stability and NP-RNA binding was evaluated. The aromatic residue of Y148 was found to stack with a nucleotide base. By interrupting the stacking interaction between Y148 and an RNA base, we identified an influenza virus NP inhibitor, (E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione; this inhibitor reduced the NP’s RNA-binding affinity and hindered viral replication. Our findings will be useful for the development of new drugs that disrupt the interaction between RNA and viral NP in the influenza virus. PMID:26916998

  1. Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development.

    PubMed

    Liu, Chia-Lin; Hung, Hui-Chen; Lo, Shou-Chen; Chiang, Ching-Hui; Chen, I-Jung; Hsu, John T-A; Hou, Ming-Hon

    2016-01-01

    Nucleoprotein (NP) is the most abundant type of RNA-binding viral protein in influenza A virus-infected cells and is necessary for viral RNA transcription and replication. Recent studies demonstrated that influenza NP is a valid target for antiviral drug development. The surface of the groove, covered with numerous conserved residues between the head and body domains of influenza A NP, plays a crucial role in RNA binding. To explore the mechanism by which NP binds RNA, we performed a series of site-directed mutagenesis in the RNA-binding groove, followed by surface plasmon resonance (SPR), to characterize the interactions between RNA and NP. Furthermore, a role of Y148 in NP stability and NP-RNA binding was evaluated. The aromatic residue of Y148 was found to stack with a nucleotide base. By interrupting the stacking interaction between Y148 and an RNA base, we identified an influenza virus NP inhibitor, (E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione; this inhibitor reduced the NP's RNA-binding affinity and hindered viral replication. Our findings will be useful for the development of new drugs that disrupt the interaction between RNA and viral NP in the influenza virus. PMID:26916998

  2. A multi-residue method for 17 anticoccidial drugs and ractopamine in animal tissues by liquid chromatography-tandem mass spectrometry and time-of-flight mass spectrometry.

    PubMed

    Matus, Johanna L; Boison, Joe O

    2016-05-01

    A new and sensitive multi-residue liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QToF-MS) method was developed and validated for the determination and confirmation of residues of 17 anticoccidials, plus free ractopamine in poultry muscle and liver, and bovine muscle, liver, and kidney tissues. The 17 anticoccidials are lasalocid, halofuginone, narasin, monensin, semduramicin, ethopabate, robenidine, buquinolate, toltrazuril as its sulfone metabolite, maduramicin, salinomycin, diclazuril, amprolium, decoquinate, dinitolmide, clopidol, and the nicarbazin metabolite DNC (N,N1-bis(4-nitrophenyl)urea). The analytes were extracted and cleaned up within a 3-hour period by simply extracting the analytes into a solvent mixture with salts followed by centrifugation, dilution, and filtration. The validated method was used in a pilot study for the analysis of 173 samples that included quail liver, bovine kidney, liver, muscle, and horse muscle. The predominant residues found in this study were monensin, ractopamine, and lasalocid. The results of this pilot study showed that this new method is applicable to real samples, and is fit for use in a regulatory testing programme. © 2016 Her Majesty the Queen in Right of Canada. Drug Testing and Analysis. © 2016 John Wiley & Sons, Ltd. PMID:27443201

  3. Inflammation and cancer: inhibiting the progression of residual hepatic VX2 carcinoma by anti-inflammatory drug after incomplete radiofrequency ablation

    PubMed Central

    Jiang, Tao; Zhang, Xianjie; Ding, Jing; Duan, Bingwei; Lu, Shichun

    2015-01-01

    significantly compared with the control group (P<0.05). Finally, the survival time of the AS-H group was longer than that of the control group (P<0.05). Conclusions: Inflammation induced by thermal destruction of the tumor following RFA could be an important cause of rapid progression of residual hepatic VX2 carcinoma. The anti-inflammation effect of aspirin can inhibit proliferation, invasion, and metastasis of residual tumor cells, and aspirin may be a good candidate drug as an adjuvant therapy with RFA for treating HCC. PMID:26823706

  4. 76 FR 16290 - Tolerances for Residues of New Animal Drugs in Food; 2-Acetylamino-5-Nitrothiazole; Buquinolate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ...) and as Sec. 556.550 (40 FR 13802 at 13956). 12. Salicylic acid (Sec. 556.590). In 2005, FDA...; Prednisolone; Prednisone; Progesterone; Propylparaben; and Salicylic Acid AGENCY: Food and Drug Administration... (44 FR 40888, July 13, 1979), but did not amend part 556 to remove the associated tolerances....

  5. Validation of a streamlined multiclass, multiresidue method for determination of veterinary drug residues in bovine muscle by liquid chromatography-tandem mass spectrometry.

    PubMed

    Schneider, Marilyn J; Lehotay, Steven J; Lightfield, Alan R

    2015-06-01

    Multiclass, multiresidue methods are becoming increasingly popular in regulatory monitoring programs due to their increased analytical scope and laboratory efficiency. In this work, we report the development and validation of a new high-throughput analytical method to monitor up to 131 veterinary drug residues, representing at least 13 different classes, in bovine muscle. This novel method streamlined sample preparation to <15 min/sample/analyst, or a batch of 40-60 pre-homogenized samples in <3 h/analyst, through the combination of dispersive solid-phase extraction with in-vial filtration (a new technique known as filter-vial d-SPE). The use of an enhanced sensitivity state-of-the-art tandem mass spectrometer led to <10 ng/g limits of quantification for nearly all drug analytes with injection of 0.17 mg of equivalent sample. Positive and negative switching in electrospray ionization was applied to cover all analytes in an 11-min liquid chromatographic separation. In the 3-day validation study, 100 of the drugs met quantification criteria of 70-120% recoveries and Horwitz Ratio ≤1.0, and the remaining analytes could still be screened at regulatory target levels. In the validation study involving >11,400 analyte results for spiked samples, the rate of false negatives for identification purposes was <5%, and no false positives occurred at appreciable concentrations. PMID:25542573

  6. Single-step extraction followed by LC for determination of (fluoro)quinolone drug residues in muscle, eggs, and milk.

    PubMed

    Cho, Hee-Jung; Yi, Hee; Cho, Soo Min; Lee, Dong Goo; Cho, Kyul; Abd el-Aty, A M; Shim, Jae-Han; Lee, Soon-Ho; Jeong, Ji-Yoon; Shin, Ho-Chul

    2010-04-01

    In this study, a simplified method for the extraction and determination of seven fluoroquinolone residues (danofloxacin, difloxacin, enrofloxacin, marbofloxacin, orbifloxacin, ofloxacin, and sarafloxacin) and three quinolones (oxolinic acid, flumequine, and nalidixic acid), in porcine muscle, table eggs, and commercial whole milk, which required no cleanup step, was devised. This procedure involves the extraction of analytes from the samples via liquid-phase extraction, and the subsequent quantitative determination was accomplished via LC-fluorescence detection. Analyte separation was successfully conducted on an XBridge-C(18) column, with a linear gradient mobile phase composed of acetonitrile and 0.01 M oxalic acid buffer at pH=3.5. The one-step liquid-liquid extraction method evidenced good selectivity, precision (RSDs=0.26-15.07%), and recovery of the extractable analytes, ranging from 61.12 to 115.93% in matrices. The LOQs ranged from 0.3 to 25 microg/kg. A survey of ten samples purchased from local markets was conducted, and none of the samples harbored fluoroquinolone residues. This method is an improvement over existing methodologies, since no additional cleanup was necessary. PMID:20175091

  7. 78 FR 37202 - Codex Alimentarius Commission: Meeting of the Codex Committee on Residues of Veterinary Drugs in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-20

    ...The Office of the Under Secretary for Food Safety, U.S. Department of Agriculture (USDA), and the Food and Drug Administration (FDA) are sponsoring a public meeting on August 5, 2013. The objective of the public meeting is to provide information and receive public comments on agenda items and draft United States positions that will be discussed at the 21st Session of the Codex Committee on......

  8. Identification of residues in ABCG2 affecting protein trafficking and drug transport, using co-evolutionary analysis of ABCG sequences

    PubMed Central

    Haider, Ameena J.; Cox, Megan H.; Jones, Natalie; Goode, Alice J.; Bridge, Katherine S.; Wong, Kelvin; Briggs, Deborah; Kerr, Ian D.

    2015-01-01

    ABCG2 is an ABC (ATP-binding cassette) transporter with a physiological role in urate transport in the kidney and is also implicated in multi-drug efflux from a number of organs in the body. The trafficking of the protein and the mechanism by which it recognizes and transports diverse drugs are important areas of research. In the current study, we have made a series of single amino acid mutations in ABCG2 on the basis of sequence analysis. Mutant isoforms were characterized for cell surface expression and function. One mutant (I573A) showed disrupted glycosylation and reduced trafficking kinetics. In contrast with many ABC transporter folding mutations which appear to be ‘rescued’ by chemical chaperones or low temperature incubation, the I573A mutation was not enriched at the cell surface by either treatment, with the majority of the protein being retained in the endoplasmic reticulum (ER). Two other mutations (P485A and M549A) showed distinct effects on transport of ABCG2 substrates reinforcing the role of TM helix 3 in drug recognition and transport and indicating the presence of intracellular coupling regions in ABCG2. PMID:26294421

  9. Rapid multi-residue and multi-class qualitative screening for veterinary drugs in foods of animal origin by UHPLC-MS/MS.

    PubMed

    Robert, C; Gillard, N; Brasseur, P-Y; Pierret, G; Ralet, N; Dubois, M; Delahaut, Ph

    2013-01-01

    Multi-class UHPLC-MS/MS was developed for the analysis of more than 160 regulated or banned compounds of various classes: anthelmintics including benzimidazoles, avermectins and others; antibiotics including amphenicols, beta-lactams, macrolides, pyrimidines, quinolones, sulphonamides and tetracyclines; beta-agonists; corticosteroids; ionophores; nitroimidazoles; non-steroidal anti-inflammatory agents; steroids; and tranquillisers. Samples were extracted with acetonitrile, without any additional purification step, and analysed by using UHPLC-MS/MS. Validation was done in accordance with the guidelines laid down by European Commission Decision 2002/657/EC for qualitative screening methods. This simple method proved applicable to routine screening for residues in egg, honey, milk and muscle samples at half the maximum concentration permitted by the European Union for each drug. In most cases, the target value was set at 5 µg kg(-1) for unauthorised compounds. PMID:23244466

  10. Evaluation of an immunobiosensor for the on-site testing of veterinary drug residues at an abattoir. Screening for sulfamethazine in pigs.

    PubMed

    Baxter, G A; O'Connor, M C; Haughey, S A; Crooks, S R; Elliott, C T

    1999-09-01

    A study was conducted to determine the feasibility of performing "on-site" screening for sulfamethazine (SMT), at an abattoir, using a rapid immunobiosensor method. This involved transfer of the biosensor technology and an assay developed in the laboratory, to the cold, humid conditions of a modern pig-processing factory. A pre-determined threshold limit of 0.4 microgram ml-1 SMT in bile was used to identify the likelihood that corresponding tissue samples contained SMT concentrations in excess of the European maximum permissible residue limit of 0.1 mg kg-1. Bile samples containing SMT concentrations above the threshold limit were deemed positive and the corresponding kidney and muscle samples were sent to the laboratory for HPLC analysis. The robustness of the biosensor instrumentation in the harsh operating conditions was monitored throughout the project. The performance of the assay, on-site, was assessed by the regular inclusion of QA samples and by the submission of control 'SMT-positive' pigs to the abattoir. Sampling procedures, identification and traceability were also under scrutiny. During the project, 337 (9.35%) of the total kill were tested for SMT residues, representing 75% of all producers submitting pigs for slaughter. Twelve animals, including the ten controls, gave positive bile results. HPLC analysis confirmed SMT residues in all 12 kidneys (11 in excess of the permissible level). Ten muscle samples also contained violative SMT levels. Throughout the project, the biosensor performed reliably, with no adverse reaction of any mechanical or electrical components. The SMT assay also performed reliably. This is the first report of a biosensor being used for 'on-site' drug screening. PMID:10736854

  11. Development of high-throughput multi-residue method for non-steroidal anti-inflammatory drugs monitoring in swine muscle by LC-MS/MS.

    PubMed

    Castilhos, Tamara S; Barreto, Fabiano; Meneghini, Leonardo; Bergold, Ana Maria

    2016-07-01

    A reliable and simple method for the detection and quantification of residues of 14 non-steroidal anti-inflammatory drugs and a metamizole metabolite in swine muscle was developed using liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS). The samples were extracted with acetonitrile (ACN) in solid-liquid extraction followed by a low-temperature partitioning (LLE-LTP) process at -20 ± 2°C. After evaporation to dryness, the residue was reconstituted with hexane and a mixture of water:acetonitrile (1:1). LC separation was achieved on a reversed-phase (RP18) column with gradient elution using water (phase A) and ACN (phase B) both containing 1 mmol l(-)(1) ammonium acetate (NH4COO) with 0.025% acetic acid. Analysis was carried out on a triple-quadrupole tandem mass spectrometer (LC-MS/MS) in multiple reaction monitoring mode using an electrospray interface in negative and positive mode in a single run. Method validation was performed according to the criteria of Commission Decision No. 2002/657/EC. The matrix effect and linearity were evaluated. Decision limit (CCα), detection capability (CCβ), accuracy and repeatability of the method are also reported. The proposed method proved to be simple, easy and adequate for high-throughput analysis and was applied to routine analysis by the Brazilian Ministry of Agriculture, Livestock and Food Supply. PMID:27268755

  12. Rapid analysis of animal drug residues by microcolumn solid-phase extraction and thermal desorption-ion trap mass spectrometry

    SciTech Connect

    Barshick, S.A.; Buchanan, M.V.

    1994-11-01

    A new approach was developed for the rapid and quantitative determination of an anthelmintic drug, phenothiazine, in milk. The technique involves a simple extraction procedure using a C{sub 18} microcolumn disc, followed by thermal desorption of the analyte from the disc directly into an ion trap mass spectrometer. The compounds are selectively ionized by isobutane chemical ionization and detected by tandem mass spectrometry. With this approach, 10 ppb detection limits were achieved with as little as 100 {mu}L mild and only 10 min of analysis time. This approach was used to analyze samples of milk taken from a cow administered a one-time therapeutic dose of phenothiazine. The target compound could be detected at 56 post-dosage, corresponding to a concentration of 30 ppb. 13 refs., 3 figs., 2 tabs.

  13. High-throughput screening of pesticide and veterinary drug residues in baby food by liquid chromatography coupled to quadrupole Orbitrap mass spectrometry.

    PubMed

    Jia, Wei; Chu, Xiaogang; Ling, Yun; Huang, Junrong; Chang, James

    2014-06-20

    A new analytical method was developed and validated for simultaneous analysis of 333 pesticide and veterinary drug residues in baby food. Response surface methodology was employed to optimize a generic extraction method. Ultrahigh-performance liquid chromatography and electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-ESI Q-Orbitrap) was used for the separation and detection of all the analytes. The method was validated by taking into consideration the guidelines specified in Commission Decision 2002/657/EC and SANCO/12571/2013. The extraction recoveries were in a range of 79.8-110.7%, with coefficient of variation <8.3%. The 333 compounds behave dynamic in the range 0.1-1000μgkg(-1) concentration, with correlation coefficient >0.99. The limits of detection for the analytes are in the range 0.01-5.35μgkg(-1). The limits of quantification for the analytes are in the range 0.01-9.27μgkg(-1). This method has been successfully applied on screening of pesticide and veterinary drugs in ninety-three commercial baby food samples, and tilmicosin, fenbendazole, tylosin tartrate and thiabendazole were detected in some samples tested in this study. The present study is very useful for fast screening of different food contaminants. PMID:24816507

  14. Simultaneous determination of 22 cephalosporins drug residues in pork muscle using liquid chromatography-tandem mass spectrometry.

    PubMed

    Li, Weiqing; Shen, Haiying; Hong, Yunhe; Zhang, Yuan; Yuan, Fei; Zhang, Feng

    2016-06-01

    A simple, sensitive and reliable analytical method was developed for the simultaneous determination of 22 common cephalosporins from the first generation to the fourth generation in pork muscle by liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method. Under the optimized extraction conditions, samples were directly purified through membrane filtration to separate all 22 cephalosporins and the critical pairs of each parent drug were completely separated. Variables affecting the LC-MS/MS were optimized to get a better separation. The excellent selectivity and sensitivity achieved in multiple reactions monitoring (MRM) mode allowed satisfactory confirmation and quantitation for the 22 cephalosporins. The linear range of the 22 cephalosporins is 0.06-100.0μg/L with good correlation coefficients (r(2)>0.9920). The limits of detection (LODs) and limits of quantitation (LOQs) of these compounds were in the range 0.04-3.0μg/L and 0.06-10.0μg/kg, respectively. The average intra-day recoveries at 3 spiked levels (LOQ, 2LOQ, 4LOQ) were all in the range 83.6-113.0% with RSDs (n=6) lower than 6.5%. The method of LC-MS/MS developed in this study was initially applied to the research of 22 cephalosporins in 12 retail pork samples and proved to be accurate, sensitive, minimum sample pre-treatment, convenient and practical. PMID:27131893

  15. Simultaneous detection of antibiotics and other drug residues in the dissolved and particulate phases of water by an off-line SPE combined with on-line SPE-LC-MS/MS: Method development and application.

    PubMed

    Tlili, Ines; Caria, Giovanni; Ouddane, Baghdad; Ghorbel-Abid, Ibtissem; Ternane, Riadh; Trabelsi-Ayadi, Malika; Net, Sopheak

    2016-09-01

    Due to their widespread use in human and animal healthcare, antibiotics and other drug residues are ubiquitous in the aquatic environment. Given their potential impacts on ecosystem functioning and public health, the quantification of environmental drug residues has become a necessity. Various analysis techniques have been found to be suitable for reliable detection of such compounds. However, quantification can be difficult because these compounds are present at trace or ultra-trace levels. Consequently, the accuracy of environmental analyses depends on both the efficiency and the robustness of the extraction and quantification method. In this work, an off-line solid-phase extraction (SPE) combined with on-line SPE-LC-MS/MS was applied to the simultaneous extraction and quantification of 26 pharmaceutical products, including 18 antibiotics, dissolved in a water phase. Optimal conditions were determined and then applied to assess the contamination level of the targeted drug residues in water collected from four sites in Northern France: a river, the input and output of an aerated lagoon, and a wastewater treatment plant. Drug residues associated with suspended solid matter (SSM) were also quantified in this work using pressurized liquid extraction (PLE) combined with an on-line SPE-LC-MS/MS system in order to complete an assessment of the degree of total background pollution. PMID:27151499

  16. Developing an Anticancer Copper(II) Pro-Drug Based on the His242 Residue of the Human Serum Albumin Carrier IIA Subdomain.

    PubMed

    Qi, Jinxu; Zhang, Yao; Gou, Yi; Zhang, Zhenlei; Zhou, Zuping; Wu, Xiaoyang; Yang, Feng; Liang, Hong

    2016-05-01

    To increase delivery efficiency, anticancer activity, and selectivity of anticancer metal agents in vivo, we proposed to develop the anticancer metal pro-drug based on His242 residue of the human serum albumin (HSA) carrier IIA subdomain. To confirm our hypothesis, we prepared two Cu(II) compounds [Cu(P4 mT)Cl and Cu(Bp44 mT)Cl] by modifying Cu(II) compound ligand structure. Studies with two HSA complex structures revealed that Cu(P4 mT)Cl bound to the HSA subdomain IIA via hydrophobic interactions, but Cu(Bp44 mT)Cl bound to the HSA subdomain IIA via His242 replacement of a Cl atom of Cu(Bp44 mT)Cl, and a coordination to Cu(2+). Furthermore, Cu(II) compounds released from HSA could be regulated at different pHs. In vivo data revealed that the HSA-Cu(Bp44 mT) complex increased copper's selectivity and capacity of inhibiting tumor growth compared to Cu(Bp44 mT)Cl alone. PMID:27017838

  17. Development and validation of a multiclass method for the determination of veterinary drug residues in chicken by ultra high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Lopes, Renata Pereira; Reyes, Rocío Cazorla; Romero-González, Roberto; Frenich, Antonia Garrido; Vidal, José Luis Martínez

    2012-01-30

    A multiclass method has been optimized and validated for the simultaneous determination of 20 veterinary drug residues belonging to several classes, as quinolones, sulfonamides, macrolides, anthelmintics, avermectins and diamino derivatives, and benzathine, used as a marker of the presence of penicillin, in muscle chicken. It has been based on QuEChERS methodology (quick, easy, cheap, effective, rugged and safe) and ultra high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry (UHPLC-MS/MS). Several chromatographic conditions were optimized, obtaining a running time <8.5 min. The developed method was validated on the basis of international guidelines. Mean recoveries ranged from 70 to 120%, except for benzathine (65.6% at 20 μg kg(-1)) and sulfadimidine (69.0% at 100 μg kg(-1)). Repeatability was lower than 20.0% except for sulfachlorpyridazine (22.1% at 20 μg kg(-1)) and tylosin (20.5% and 20.6% at 30 and 50 μg kg(-1), respectively), whereas reproducibility was lower than 25% except for flumequine (27.4% at 20 μg kg(-1)) and benzathine (37.8% and 27% at 20 and 50 μg kg(-1), respectively). Limits of detection (LODs) and quantification (LOQs) ranged from 3.0 to 6.0 μg kg(-1) and 10.0 to 20.0 μg kg(-1), respectively, except for tylosin that showed a LOD and LOQ of 9.0 and 30.0 μg kg(-1). Decision limit (CC(α)) and detection capability (CC(β)) were calculated and CC(β) ranged from 24.1 μg kg(-1) (mebendazole) to 423.6 μg kg(-1) (flumequine). Finally, the method was applied to real samples and traces of some compounds were found in eight samples of chicken and benzathine was detected in one sample at 29.9 μg kg(-1). PMID:22284481

  18. Development and validation of a method for the confirmation of nicarbazin in chicken liver and eggs using LC-electrospray MS-MS according to the revised EU criteria for veterinary drug residue analysis.

    PubMed

    Yakkundi, S; Cannavan, A; Elliott, C T; Lovgren, T; Kennedy, D G

    2001-11-01

    A method is described for the quantitative confirmation of 4,4'-dinitrocarbanilide (DNC), the marker residue for nicarbazin in chicken liver and eggs. The method is based on LC coupled to negative ion electrospray MS-MS of tissue extracts prepared by liquid-liquid extraction. The [M-H]- ion at m/z 301 is monitored along with two transition ions at m/z 137 and 107 for DNC and the [M-H]- ion at m/z 309 for the internal standard, d8-DNC. The method has been validated according to the new EU criteria for the analysis of veterinary drug residues at 100, 200 and 300 microg kg(-1) in liver and at 10, 30 and 100 microg kg(-1) in eggs. Difficulties concerning the application of the new analytical limits, namely the decision limit (CCalpha) and the detection capability (CCbeta) to the determination of DNC in both liver and eggs are discussed. PMID:11763079

  19. Application of a hybrid ordered mesoporous silica as sorbent for solid-phase multi-residue extraction of veterinary drugs in meat by ultra-high-performance liquid chromatography coupled to ion-trap tandem mass spectrometry.

    PubMed

    Casado, Natalia; Morante-Zarcero, Sonia; Pérez-Quintanilla, Damián; Sierra, Isabel

    2016-08-12

    A quick, sensitive and selective analytical reversed-phase multi-residue method using ultra-high performance liquid chromatography coupled to an ion-trap mass spectrometry detector (UHPLC-IT-MS/MS) operating in both positive and negative ion mode was developed for the simultaneous determination of 23 veterinary drug residues (β-blockers, β-agonists and Non-Steroidal Anti-inflammatory Drugs (NSAIDs)) in meat samples. The sample treatment involved a liquid-solid extraction followed by a solid-phase extraction (SPE) procedure. SBA-15 type mesoporous silica was synthetized and modified with octadecylsilane, and the resulting hybrid material (denoted as SBA-15-C18) was applied and evaluated as SPE sorbent in the purification of samples. The materials were comprehensively characterized, and they showed a high surface area, high pore volume and a homogeneous distribution of the pores. Chromatographic conditions and extraction procedure were optimized, and the method was validated according to the Commission Decision 2002/657/EC. The method detection limits (MDLs) and the method quantification limits (MQLs) were determined for all the analytes in meat samples and found to range between 0.01-18.75μg/kg and 0.02-62.50μg/kg, respectively. Recoveries for 15 of the target analytes ranged from 71 to 98%. In addition, for comparative purpose SBA-15-C18 was evaluated towards commercial C18 amorphous silica. Results revealed that SBA-15-C18 was clearly more successful in the multi-residue extraction of the 23 mentioned analytes with higher recovery values. The method was successfully tested to analyze prepacked preparations of mince bovine meat. Traces of propranolol, ketoprofen and diclofenac were detected in some samples. PMID:27412322

  20. BioHCVKD: a bioinformatics knowledge discovery system for HCV drug discovery - identifying proteins, ligands and active residues, in biological literature.

    PubMed

    Seoud, Rania Ahmed Abdel Azzem Abdel Rahman Abul

    2011-01-01

    Hepatitis C Virus (HCV) causes significant morbidity worldwide with restricted treatment options and lack of a universal cure which necessitate design of novel drugs. Researchers face an enormous growth of literature with very small portions of HCV knowledge accessible in structured way. This paper proposes the BioHCVKD that helps researchers to annotate relevant HCV information targeted to accelerate HCV drug discovery. BioHCVKD combines the dictionary based filtering and conditional random field (CRF) based gene mention tagger. BioHCVKD is supported by two modules, the Abstract Insertion module, and the Protein Insertion module. BioHCVKD achieves a recall of 73.25%, a precision of 70.5% and F-score of 71.85%, which improves the performance of the name entity tagger. PMID:21816718

  1. Multi-class, multi-residue analysis of trace veterinary drugs in milk by rapid screening and quantification using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

    PubMed

    Zhang, Yaqian; Li, Xiang; Liu, Xiaomao; Zhang, Jinjie; Cao, Yanzhong; Shi, Zhihong; Sun, Hanwen

    2015-12-01

    A simple and rapid multi-class multi-residue analytical method was developed for the screening and quantification of veterinary drugs in milk by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). A total of 90 veterinary drugs investigated belonged to almost 20 classes including lincomycins, macrolides, sulfonamides, quinolones, tetracyclines, β-agonists, β-lactams, sedatives, β-receptor antagonists, sex hormones, glucocorticoids, nitroimidazoles, benzimidazoles, nitrofurans, and some others. A modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) procedure was developed for the sample preparation without the solid-phase extraction step. The linearity, sensitivity, accuracy, repeatability, and reproducibility of the method were fully validated. The response of the detector was linear for each target compound in a wide concentration range with a correlation coefficient (R(2)) of 0.9973 to 0.9999 (among them R(2)>0.999 for 73 of 90 analytes). The range of the limit of quantification for these compounds in the milk ranged from 0.10 to 17.30μg/kg. The repeatability and reproducibility were in the range of 2.11 to 9.62% and 2.76 to 13.9%, respectively. The average recoveries ranged from 72.62 to 122.2% with the RSD (n=6) of 1.30 to 9.61% at 3 concentration levels. For the screening method, the data of the precursor and product ions of the target analytes were simultaneously acquired under the all ions MS/MS mode in a single run. An accurate mass database for the confirmation and identification of the target compounds was established. The applicability of the screening method was verified by applying to real milk samples. The proposed analytical method allows the identification and confirmation of the target veterinary drugs at trace levels employing quick analysis time. Certain veterinary drugs were detected in some cases. PMID:26506545

  2. Crop residues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crop residues [e.g., corn (Zea mays) stover and small grain straw] are sometimes excluded when discussing cellulosic energy crops per se, but because of the vast area upon which they are grown and their current role in the development of cellulosic energy systems. This chapter focuses on current cor...

  3. Validation and uncertainties evaluation of an isotope dilution-SPE-LC-MS/MS for the quantification of drug residues in surface waters.

    PubMed

    Brieudes, V; Lardy-Fontan, S; Lalere, B; Vaslin-Reimann, S; Budzinski, H

    2016-01-01

    The present work describes the development and validation of a reference method conducted at the French National Institute of Metrology (LNE) for the quantitative determination of psychoactive compounds in the dissolved fraction of surface waters. More specifically an isotope dilution-SPE-LC-MS/MS based method has been implemented for the characterization of a broad range of analytes belonging to different classes of psychotropic drugs such as benzodiazepines, antidepressants, stimulants, opiates and opioids, anticonvulsants, anti-dementia drugs, analgesics as well as the anti-inflammatory drug diclofenac in the low ng L(-1) range of concentration. Full validation of the method was performed following procedures described by the French standard NF T90-210. Limits of quantification between 0.14 and 3.54 ng L(-1) were obtained. Method recoveries from 71 to 123% were observed with standard deviation below 10% in intermediate precision conditions. Accuracy was determined for every compound: measurement errors were between -4 and +1% and standard deviations in intermediate precision conditions were included within a 1-9% interval. Finally, measurement uncertainties were evaluated following the Guide to the expression of uncertainty in measurement (GUM). Expanded uncertainties (k=2) ranged from 2% for carbamazepine, EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) and venlafaxine to 17% for diazepam. The validated method was implemented to Seine river surface waters demonstrating its fitness for purpose. All compounds were detected and 22 out of 25 analytes were quantified. More specifically, measured concentration ranged from 0.39 ng L(-1) for MDMA (3,4-methylene-dioxy-N-methylamphetamine) to 182 ng L(-1) for gabapentine. PMID:26695245

  4. Mutation of G234 amino acid residue in Candida albicans drug-resistance-related protein Rta2p is associated with fluconazole resistance and dihydrosphingosine transport

    PubMed Central

    Zhang, Shi-Qun; Miao, Qi; Li, Li-Ping; Zhang, Lu-lu; Yan, Lan; Jia, Yu; Cao, Yong-Bing; Jiang, Yuan-Ying

    2015-01-01

    Widespread and repeated use of azoles has led to the rapid development of drug resistance in Candida albicans. Our previous study found Rta2p, a membrane protein with 7 transmembrane domains, was involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in C. albicans. Conserved amino acids in the transmembrane domain of Rta2p were subjected to site-directed mutagenesis. The sensitivity of C. albicans to fluconazole in vitro was examined by minimum inhibitory concentration and killing assay, and the therapeutic efficacy of fluconazole in vivo was performed by systemic mice candidiasis model. Furthermore, dihydrosphingosine transport activity was detected by NBD labeled D-erythro-dihydrosphingosine uptake and release assay, and the sensitivity to sphingolipid biosynthesis inhibitors. We successfully constructed 14 mutant strains of Rta2p, screened them by minimum inhibitory concentration and found Ca2+ did not completely induce fluconazole resistance with G158E and G234S mutations. Furthermore, we confirmed that G234S mutant enhanced the therapeutic efficacy of fluconazole against systemic candidiasis and significantly increased the accumulation of dihydrosphingosine by decreasing its release. However, G158E mutant didn't affect drug therapeutic efficacy in vivo and dihydrosphingosine transport in C. albicans. G234 of Rta2p in C. albicans is crucial in calcineurin-mediated fluconazole resistance and dihydrosphingosine transport. PMID:26220356

  5. Mutation of G234 amino acid residue in candida albicans drug-resistance-related protein Rta2p is associated with fluconazole resistance and dihydrosphingosine transport.

    PubMed

    Zhang, Shi-Qun; Miao, Qi; Li, Li-Ping; Zhang, Lu-Lu; Yan, Lan; Jia, Yu; Cao, Yong-Bing; Jiang, Yuan-Ying

    2015-01-01

    Widespread and repeated use of azoles has led to the rapid development of drug resistance in Candida albicans. Our previous study found Rta2p, a membrane protein with 7 transmembrane domains, was involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in C. albicans. Conserved amino acids in the transmembrane domain of Rta2p were subjected to site-directed mutagenesis. The sensitivity of C. albicans to fluconazole in vitro was examined by minimum inhibitory concentration and killing assay, and the therapeutic efficacy of fluconazole in vivo was performed by systemic mice candidiasis model. Furthermore, dihydrosphingosine transport activity was detected by NBD labeled D-erythro-dihydrosphingosine uptake and release assay, and the sensitivity to sphingolipid biosynthesis inhibitors. We successfully constructed 14 mutant strains of Rta2p, screened them by minimum inhibitory concentration and found Ca(2+) did not completely induce fluconazole resistance with G158E and G234S mutations. Furthermore, we confirmed that G234S mutant enhanced the therapeutic efficacy of fluconazole against systemic candidiasis and significantly increased the accumulation of dihydrosphingosine by decreasing its release. However, G158E mutant didn't affect drug therapeutic efficacy in vivo and dihydrosphingosine transport in C. albicans. G234 of Rta2p in C. albicans is crucial in calcineurin-mediated fluconazole resistance and dihydrosphingosine transport. PMID:26220356

  6. Distribution of Penicillin G Residues in Culled Dairy Cow Muscles: Implications for Residue Monitoring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The U.S. Food and Drug Administration sets tolerances for veterinary drug residues in muscle, but does not specify which type of muscle should be analyzed. In order to determine if antibiotic residue levels are dependent on muscle type, 7 culled dairy cows were dosed with Penicillin G (Pen G) from ...

  7. Multi-class method for determination of veterinary drug residues and other contaminants in infant formula by ultra performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhan, Jia; Zhong, Ying-ying; Yu, Xue-jun; Peng, Jin-feng; Chen, Shubing; Yin, Ju-yi; Zhang, Jia-Jie; Zhu, Yan

    2013-06-01

    A rapid, simple and generic analytical method which was able to simultaneously determine 220 undesirable chemical residues in infant formula had been developed. The method comprised of extraction with acetonitrile, clean-up by low temperature and water precipitation, and analysis by ultra performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS-MS) using multiple reaction monitoring (MRM) mode. Most fat materials in acetonitrile extract were eliminated by low temperature clean-up. The water precipitation, providing a necessary and supplementary cleanup, could avoid losses of hydrophobic analytes (avermectins, ionophores). Average recoveries for spiked infant formula were in the range from 57% to 147% with associated RSD values between 1% and 28%. For over 80% of the analytes, the recoveries were between 70% and 120% with RSD values in the range of 1-15%. The limits of quantification (LOQs) were from 0.01 to 5 μg/kg, which were usually sufficient to verify the compliance of products with legal tolerances. Application of this method in routine monitoring programs would imply a drastic reduction of both effort and time. PMID:23411184

  8. Improved Cross Validation of a Static Ubiquitin Structure Derived from High Precision Residual Dipolar Couplings Measured in a Drug-Based Liquid Crystalline Phase

    PubMed Central

    2014-01-01

    The antibiotic squalamine forms a lyotropic liquid crystal at very low concentrations in water (0.3-3.5% w/v), which remains stable over a wide range of temperature (1-40 °C) and pH (4-8). Squalamine is positively charged, and comparison of the alignment of ubiquitin relative to 36 previously reported alignment conditions shows that it differs substantially from most of these, but is closest to liquid crystalline cetyl pyridinium bromide. High precision residual dipolar couplings (RDCs) measured for the backbone 1H-15N, 15N-13C′, 1Hα-13Cα, and 13C′-13Cα one-bond interactions in the squalamine medium fit well to the static structural model previously derived from NMR data. Inclusion into the structure refinement procedure of these RDCs, together with 1H-15N and 1Hα-13Cα RDCs newly measured in Pf1, results in improved agreement between alignment-induced changes in 13C′ chemical shift, 3JHNHα values, and 13Cα-13Cβ RDCs and corresponding values predicted by the structure, thereby validating the high quality of the single-conformer structural model. This result indicates that fitting of a single model to experimental data provides a better description of the average conformation than does averaging over previously reported NMR-derived ensemble representations. The latter can capture dynamic aspects of a protein, thus making the two representations valuable complements to one another. PMID:24568736

  9. Rapid determination of 88 veterinary drug residues in milk using automated TurborFlow online clean-up mode coupled to liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhu, Wei-xia; Yang, Ji-zhou; Wang, Zhao-xing; Wang, Cai-juan; Liu, Ya-feng; Zhang, Li

    2016-02-01

    A novel method based on TurborFlow online solid phase extraction (SPE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been established for simultaneous screening and confirmation of 88 wide-range veterinary drugs belonging to eight families (20 sulfonamides, 7 macrolides, 15 quinolones, 8 penicillins, 13 benzimidazoles, 4 tetracyclines, 2 sedatives, and 19 hormones) in milk. The preparation method consists of sample dilution and ultrasonic extraction, followed by an automated turbulent flow cyclone chromatography sample clean-up system. The detection was achieved in selected reaction monitoring mode (SRM). The total run time was within 39 min, including automated extraction, analytical chromatography and re-equilibration of the turboflow system. The optimization of different experimental parameters including extraction, purification, separation, and detection were evaluated separately in this study. The developed method was validated and good performing characteristics were obtained. The linear regression coefficients (R(2)) of matrix-match calibration standard curves established for quantification were higher than 0.9930. The limits of detection (LOD) were in the range of 0.2-2.0 μg/kg given by signal-noise ratio ≥3 (S/N) and the limits of quantification (LOQ, S/N≥10) ranged between 0.5 μg/kg and 10 μg/kg. Average recoveries of spiked target compounds with different levels were between 63.1% and 117.4%, with percentage relative standard deviations (RSD) in the range of 3.3-17.6%. The results indicated that the developed method has great potential for the routine laboratory analysis of large numbers of samples on measuring different classes of compounds. In comparison to traditional procedures, the automated sample clean-up ensures rapid, effective, sensitive analyses of veterinary drugs in milk. PMID:26653466

  10. A combined liquid chromatography-triple-quadrupole mass spectrometry method for the residual detection of veterinary drugs in porcine muscle, milk, and eggs.

    PubMed

    Zhang, Dan; Park, Zee-Yong; Park, Jin-A; Kim, Seong-Kwan; Jeong, Daun; Cho, Sang-Hyun; Shim, Jae-Han; Kim, Jin-Suk; Abd El-Aty, A M; Shin, Ho-Chul

    2016-06-01

    A liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method was developed for monitoring and detection of four different drugs, namely acetanilide, pentylenetetrazole, phenacetin, and tetramethrin in porcine muscle, pasteurized milk, and table egg samples. For acetanilide and pentylenetetrazole, the samples were extracted with 0.1 % formic acid in acetonitrile, followed by defatting with n-hexane, partitioning at -20 °C for 1 h, centrifugation, and filtration, whereas the quick, easy, cheap, effective, rugged, and safe "QuEChERS" method was used for phenacetin and tetramethrin. The final extracts were combined and analyzed in a single chromatographic run using an XBridge(TM) analytical column and 0.1 % formic acid and 10 mM ammonium formate in ultrapure water (A) and 0.1 % formic acid and 10 mM ammonium formate in methanol (B) as the mobile phase. Owing to the unavailability of internal standards, matrix-matched calibrations were used for analyte quantification with coefficients of determination (R (2)) ≥ 0.9865. The intra- and inter-day accuracies ranged from 60.75 to 90.90 % and from 63.75 to 89.30 %, respectively, while the respective analytical precisions were 1.48-17.44 % (23.3 % for porcine sample spiked with phenacetin) and 1.97-15.78 %. The limits of quantification (LOQ) were between 0.5 and 2.5 ng/g in the matrices tested. Food samples purchased from local markets in Seoul were analyzed using the developed method and none of the tested drugs was detected. PMID:27178050

  11. An analytical method to screen for six thyreostatic drug residues in the thyroid gland and muscle tissues of food producing animals by liquid chromatography with ultraviolet absorption detection and liquid chromatography/mass spectrometry.

    PubMed

    Asea, Philip E; MacNeil, James D; Boison, Joe O

    2006-01-01

    A method was developed and validated to screen for residues of the thyreostatic drugs, tapazole (TAP), mercaptobenzimidazole (MBI), thiouracil (TU), methylthiouracil (MTU), propylthiouracil (PrTU), and phenylthiouracil (PhTU) in bovine, equine, ovine, and porcine thyroid and muscle tissues at concentrations > or = 5 ng/g using 2-methoxy-mercaptobenzimidazole (MeMBI) and dimethylthiouracil (DMTU) as internal standards. In this method, the drugs were solvent extracted from thyroid and muscle tissue and cleaned up on an amino-propyl solid-phase extraction (SPE) cartridge. The unretained fraction containing TAP and MBI and the internal standard, MeMBI, was collected as Fraction 1. The retained fraction containing TU, MTU, PrTU, PhTU, and the internal standard, DMTU, was eluted with 3% acetic acid-isopropanol as Fraction 2. Fraction 1 was further cleaned up on an alumina B SPE cartridge and analyzed by gradient elution on a C18 high-performance liquid chromatography (HPLC) column with ultraviolet detection at wavelengths of 255 and 300 nm. Fraction 2 was taken to dryness, derivatized with 4-chloro-7-nitrobenzo-2-furazan at pH 8, and analyzed by gradient elution on a C18 LC column with mass spectrometry (MS) detection. Any "presumptive positive" test results were submitted for further analysis by LC/MS/MS. The validated method was applied to the analysis of over 300 thyroid tissue samples. PMID:16640308

  12. Improved cross validation of a static ubiquitin structure derived from high precision residual dipolar couplings measured in a drug-based liquid crystalline phase.

    PubMed

    Maltsev, Alexander S; Grishaev, Alexander; Roche, Julien; Zasloff, Michael; Bax, Ad

    2014-03-12

    The antibiotic squalamine forms a lyotropic liquid crystal at very low concentrations in water (0.3-3.5% w/v), which remains stable over a wide range of temperature (1-40 °C) and pH (4-8). Squalamine is positively charged, and comparison of the alignment of ubiquitin relative to 36 previously reported alignment conditions shows that it differs substantially from most of these, but is closest to liquid crystalline cetyl pyridinium bromide. High precision residual dipolar couplings (RDCs) measured for the backbone (1)H-(15)N, (15)N-(13)C', (1)H(α)-(13)C(α), and (13)C'-(13)C(α) one-bond interactions in the squalamine medium fit well to the static structural model previously derived from NMR data. Inclusion into the structure refinement procedure of these RDCs, together with (1)H-(15)N and (1)H(α)-(13)C(α) RDCs newly measured in Pf1, results in improved agreement between alignment-induced changes in (13)C' chemical shift, (3)JHNHα values, and (13)C(α)-(13)C(β) RDCs and corresponding values predicted by the structure, thereby validating the high quality of the single-conformer structural model. This result indicates that fitting of a single model to experimental data provides a better description of the average conformation than does averaging over previously reported NMR-derived ensemble representations. The latter can capture dynamic aspects of a protein, thus making the two representations valuable complements to one another. PMID:24568736

  13. Impact of Hemoglobin A1c Levels on Residual Platelet Reactivity and Outcomes After Insertion of Coronary Drug-Eluting Stents (from the ADAPT-DES Study).

    PubMed

    Schoos, Mikkel M; Dangas, George D; Mehran, Roxana; Kirtane, Ajay J; Yu, Jennifer; Litherland, Claire; Clemmensen, Peter; Stuckey, Thomas D; Witzenbichler, Bernhard; Weisz, Giora; Rinaldi, Michael J; Neumann, Franz-Josef; Metzger, D Christopher; Henry, Timothy D; Cox, David A; Duffy, Peter L; Brodie, Bruce R; Mazzaferri, Ernest L; Maehara, Akiko; Stone, Gregg W

    2016-01-15

    An increasing hemoglobin A1c (HbA1c) level portends an adverse cardiovascular prognosis; however, the association between glycemic control, platelet reactivity, and outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is unknown. We sought to investigate whether HbA1c levels are associated with high platelet reactivity (HPR) in patients loaded with clopidogrel and aspirin, thereby constituting an argument for intensified antiplatelet therapy in patients with poor glycemic control. In the prospective, multicenter Assessment of Dual Antiplatelet Therapy With Drug Eluting Stents registry, HbA1c levels were measured as clinically indicated in 1,145 of 8,582 patients, stratified by HbA1c <6.5% (n = 551, 48.12%), 6.5% to 8.5% (n = 423, 36.9%), and >8.5% (n = 171, 14.9%). HPR on clopidogrel and aspirin was defined after PCI as P2Y12 reaction units (PRU) >208 and aspirin reaction units >550, respectively. HPR on clopidogrel was frequent (48.3%), whereas HPR on aspirin was not (3.9%). Patients with HbA1c >8.5% were younger, more likely non-Caucasian, had a greater body mass index, and more insulin-treated diabetes and acute coronary syndromes. Proportions of PRU >208 (42.5%, 50.2%, and 62.3%, p <0.001) and rates of definite or probable stent thrombosis (ST; 0.9%, 2.7%, and 4.2%, p = 0.02) increased progressively with HbA1c groups. Clinically relevant bleeding was greatest in the intermediate HbA1c group (8.2% vs 13.1% vs 9.5%, p = 0.04). In adjusted models that included PRU, high HbA1c levels (>8.5) remained associated with ST (hazard ratio 3.92, 95% CI 1.29 to 12.66, p = 0.02) and cardiac death (hazard ratio 4.24, 95% CI 1.41 to 12.70) but not bleeding at 2-year follow-up. There was no association between aspirin reaction units >550 and HbA1c levels. In conclusion, in this large-scale study, HbA1c and HPR were positively associated, but the clinical effect on adverse outcome was driven by poor glycemic control, which predicted ST and

  14. Development of a multi-residue method for fast screening and confirmation of 20 prohibited veterinary drugs in feedstuffs by liquid chromatography tandem mass spectrometry.

    PubMed

    Zhang, Gui-Jun; Fang, Bing-Hu; Liu, Ya-Hong; Wang, Xu-Feng; Xu, Li-Xiao; Zhang, Ya-Ping; He, Li-Min

    2013-10-01

    A simple multiresidue method was developed for detecting and quantifying twenty analytes from 5 classes of prohibited veterinary drugs (β-agonists (9), anabolic hormones (4), quinoxalines (4), tranquilizers (1), cyproheptadine, and clonidine in animal feeds using a QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) approach. Feed samples were extracted by ultrasonic-assisted extraction with a mixture of methanol-acetonitrile (50:50, v/v), followed by a cleanup using a dispersive solid-phase extraction with PSA (primary secondary amine). Target compounds were separated and determined by a liquid chromatography tandem quadrupole mass spectrometer operating in positive electrospray ionization mode, using multiple reaction monitoring (MRM). The recoveries of these compounds were between 56.7% and 103% at three spiked levels. The repeatability was lower than 10%, whereas reproducibility was no more than 15% except for nandrolone (17% at 10μgkg(-1)) and diazepam (19% at 10μgkg(-1)). Decision limits (CCαs) and detection capabilities (CCβs) ranged from 0.42 to 5.74μgkg(-1) and 5.70-9.81μgkg(-1), respectively. The method was successfully applied to screening of real samples obtained from local feed markets and confirmation of the suspected target analytes. PMID:23962505

  15. Metabolic Disposition of Osimertinib in Rats, Dogs, and Humans: Insights into a Drug Designed to Bind Covalently to a Cysteine Residue of Epidermal Growth Factor Receptor.

    PubMed

    Dickinson, Paul A; Cantarini, Mireille V; Collier, Jo; Frewer, Paul; Martin, Scott; Pickup, Kathryn; Ballard, Peter

    2016-08-01

    Preclinical and clinical studies were conducted to determine the metabolism and pharmacokinetics of osimertinib and key metabolites AZ5104 and AZ7550. Osimertinib was designed to covalently bind to epidermal growth factor receptors, allowing it to achieve nanomolar cellular potency (Finlay et al., 2014). Covalent binding was observed in incubations of radiolabeled osimertinib with human and rat hepatocytes, human and rat plasma, and human serum albumin. Osimertinib, AZ5104, and AZ7550 were predominantly metabolized by CYP3A. Seven metabolites were detected in human hepatocytes, also observed in rat or dog hepatocytes at similar or higher levels. After oral administration of radiolabeled osimertinib to rats, drug-related material was widely distributed, with the highest radioactivity concentrations measured at 6 hours postdose in most tissues; radioactivity was detectable in 42% of tissues 60 days postdose. Concentrations of [(14)C]-radioactivity in blood were lower than in most tissues. After the administration of a single oral dose of 20 mg of radiolabeled osimertinib to healthy male volunteers, ∼19% of the dose was recovered by 3 days postdose. At 84 days postdose, mean total radioactivity recovery was 14.2% and 67.8% of the dose in urine and feces. The most abundant metabolite identified in feces was AZ5104 (∼6% of dose). Osimertinib accounted for ∼1% of total radioactivity in the plasma of non-small cell lung cancer patients after 22 days of 80-mg osimertinib once-daily treatment; the most abundant circulatory metabolites were AZ7550 and AZ5104 (<10% of total osimertinib-related material). Osimertinib is extensively distributed and metabolized in humans and is eliminated primarily via the fecal route. PMID:27226351

  16. A critical assessment of the performance criteria in confirmatory analysis for veterinary drug residue analysis using mass spectrometric detection in selected reaction monitoring mode.

    PubMed

    Berendsen, Bjorn J A; Meijer, Thijs; Wegh, Robin; Mol, Hans G J; Smyth, Wesley G; Armstrong Hewitt, S; van Ginkel, Leen; Nielen, Michel W F

    2016-05-01

    Besides the identification point system to assure adequate set-up of instrumentation, European Commission Decision 2002/657/EC includes performance criteria regarding relative ion abundances in mass spectrometry and chromatographic retention time. In confirmatory analysis, the relative abundance of two product ions, acquired in selected reaction monitoring mode, the ion ratio should be within certain ranges for confirmation of the identity of a substance. The acceptable tolerance of the ion ratio varies with the relative abundance of the two product ions and for retention time, CD 2002/657/EC allows a tolerance of 5%. Because of rapid technical advances in analytical instruments and new approaches applied in the field of contaminant testing in food products (multi-compound and multi-class methods) a critical assessment of these criteria is justified. In this study a large number of representative, though challenging sample extracts were prepared, including muscle, urine, milk and liver, spiked with 100 registered and banned veterinary drugs at levels ranging from 0.5 to 100 µg/kg. These extracts were analysed using SRM mode using different chromatographic conditions and mass spectrometers from different vendors. In the initial study, robust data was collected using four different instrumental set-ups. Based on a unique and highly relevant data set, consisting of over 39 000 data points, the ion ratio and retention time criteria for applicability in confirmatory analysis were assessed. The outcomes were verified based on a collaborative trial including laboratories from all over the world. It was concluded that the ion ratio deviation is not related to the value of the ion ratio, but rather to the intensity of the lowest product ion. Therefore a fixed ion ratio deviation tolerance of 50% (relative) is proposed, which also is applicable for compounds present at sub-ppb levels or having poor ionisation efficiency. Furthermore, it was observed that retention time

  17. Residual Cap

    NASA Technical Reports Server (NTRS)

    2006-01-01

    10 May 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a summertime view of the south polar residual cap of Mars. In this image, mesas composed largely of solid carbon dioxide are separated from one another by irregularly-shaped depressions. The variation in brightness across this scene is a function of several factors including, but not limited to, varying proportions of dust and solid carbon dioxide, undulating topography, and differences in the roughness of the slopes versus the flat surfaces.

    Location near: 86.7oS, 343.3oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Summer

  18. Multi-residue analysis of veterinary drugs, pesticides and mycotoxins in dairy products by liquid chromatography-tandem mass spectrometry using low-temperature cleanup and solid phase extraction.

    PubMed

    Xie, Jie; Peng, Tao; Zhu, Ailing; He, Jianli; Chang, Qiaoying; Hu, Xueyan; Chen, Hui; Fan, Chunlin; Jiang, Wenxiao; Chen, Min; Li, Jiancheng; Ding, Shuangyang; Jiang, Haiyang

    2015-10-01

    A multi-class multi-residue analysis method for determination of veterinary drugs, pesticides and mycotoxins in dairy products by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been established. These 17 classes, a total of 40 kinds of target compounds were chosen because their administration to food-producing animals is banned or regulated in China and may be potentially abused or misused. Samples were extracted with acetonitrile-ethyl acetate-acetic acid (49.5+49.5+1, v/v/v). Most of lipids in the extract were removed by low-temperature cleanup, prior to solid phase extraction on HLB cartridges. The quantification and confirmation of the 40 analytes were performed by LC-MS/MS with electro-spray ionization (ESI) interface in multiple reaction monitoring (MRM) mode. The limits of detection (LODs) and limits of quantification (LOQs) were 0.006-0.3μg/kg and 0.02-1.0μg/kg, respectively. The spiked recoveries in milk, yogurt, milk powder and cheese samples were from 67.3% to 106.9%. The repeatability and the within-laboratory reproducibility were less than 12.7% and 13.9%. Applying this method, our results revealed the presences of chloramphenicol, cimeterol, and flunixin at the concentration of 0.027-0.452μg/kg in some samples. PMID:26298066

  19. 40 CFR 161.240 - Residue chemistry data requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... requirement if their residues are regulated by the Food and Drug Administration at 21 CFR 178.1010. (11... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Residue chemistry data requirements... § 161.240 Residue chemistry data requirements. (a) Table. Sections 161.100 through 161.102 describe...

  20. 40 CFR 161.240 - Residue chemistry data requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... requirement if their residues are regulated by the Food and Drug Administration at 21 CFR 178.1010. (11... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Residue chemistry data requirements... § 161.240 Residue chemistry data requirements. (a) Table. Sections 161.100 through 161.102 describe...

  1. 40 CFR 161.240 - Residue chemistry data requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requirement if their residues are regulated by the Food and Drug Administration at 21 CFR 178.1010. (11... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Residue chemistry data requirements... § 161.240 Residue chemistry data requirements. (a) Table. Sections 161.100 through 161.102 describe...

  2. 40 CFR 161.240 - Residue chemistry data requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirement if their residues are regulated by the Food and Drug Administration at 21 CFR 178.1010. (11... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Residue chemistry data requirements... § 161.240 Residue chemistry data requirements. (a) Table. Sections 161.100 through 161.102 describe...

  3. 77 FR 24671 - Compliance Guide for Residue Prevention and Agency Testing Policy for Residues

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ... increased testing animals from producers who are under an injunction obtained by the Food and Drug... addition, FSIS intends to increase its testing for residues in animals from producers who are under an... Food Safety and Inspection Service Compliance Guide for Residue Prevention and Agency Testing...

  4. Salinomycin residues and their ionophoricity in pig tissues

    SciTech Connect

    Dimenna, G.P.; Lyon, F.S.; Creegan, J.A. ); Wright, G.J. ); Wilkes, L.C. ); Johnson, D.E.; Szymanski, T. )

    1990-04-01

    The effect of pretreatment with medicated feed on ({sup 14}C) salinomycin residue levels in pig tissues was studied. Pigs were fed unmedicated feed or feed medicated with salinomycin at 41 ppm in the diet for 29 days and then dosed with ({sup 14}C)salinomycin for 8 days. Total drug residue levels were below quantifiable limits of detection of kidney, fat, and muscle but at the tolerance limit of 1,800 ppb for liver. In liver, pretreatment tended to lower total residue levels, and unchanged ({sup 14}C)salinomycin accounted for <1% of the total drug residue. Approximately 15-20% of the total drug residue in liver was bound. Ionophoric activity in extracts of livers from the treated pigs was minimal, and only 2 of the 12 treated samples had ionophoric activity more than twice that obtained from the controls.

  5. 21 CFR 500.86 - Marker residue and target tissue.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Regulation of Carcinogenic Compounds Used in Food... tissues and, therefore, that the residue of carcinogenic concern in the diet of people does not exceed...

  6. 21 CFR 500.86 - Marker residue and target tissue.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Regulation of Carcinogenic Compounds Used in Food... tissues and, therefore, that the residue of carcinogenic concern in the diet of people does not exceed...

  7. Club Drugs

    MedlinePlus

    ... Rohypnol, ketamine, as well as MDMA (ecstasy) and methamphetamine ( Drug Facts: Club Drugs , National Institute on Drug ... Club Drugs , National Institute on Drug Abuse, 2010). Methamphetamine is a powerfully addictive stimulant associated with serious ...

  8. 21 CFR 173.250 - Methyl alcohol residues.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Methyl alcohol residues. 173.250 Section 173.250... CONSUMPTION Solvents, Lubricants, Release Agents and Related Substances § 173.250 Methyl alcohol residues. Methyl alcohol may be present in the following foods under the conditions specified: (a) In...

  9. 21 CFR 173.250 - Methyl alcohol residues.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Methyl alcohol residues. 173.250 Section 173.250... CONSUMPTION Solvents, Lubricants, Release Agents and Related Substances § 173.250 Methyl alcohol residues. Methyl alcohol may be present in the following foods under the conditions specified: (a) In...

  10. 21 CFR 173.250 - Methyl alcohol residues.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Methyl alcohol residues. 173.250 Section 173.250... and Related Substances § 173.250 Methyl alcohol residues. Methyl alcohol may be present in the... specifies the presence of methyl alcohol and provides for the use of the hops extract only as prescribed...

  11. 21 CFR 173.250 - Methyl alcohol residues.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Methyl alcohol residues. 173.250 Section 173.250... CONSUMPTION Solvents, Lubricants, Release Agents and Related Substances § 173.250 Methyl alcohol residues. Methyl alcohol may be present in the following foods under the conditions specified: (a) In...

  12. 21 CFR 173.250 - Methyl alcohol residues.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Methyl alcohol residues. 173.250 Section 173.250... CONSUMPTION Solvents, Lubricants, Release Agents and Related Substances § 173.250 Methyl alcohol residues. Methyl alcohol may be present in the following foods under the conditions specified: (a) In...

  13. Drug allergies

    MedlinePlus

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  14. Club Drugs

    MedlinePlus

    ... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...

  15. Drug allergies

    MedlinePlus

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... Adverse reactions to drugs are common. (adverse means unwanted or unexpected.) Almost any drug can cause an adverse reaction. Reactions range from irritating ...

  16. Drug Safety

    MedlinePlus

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  17. Drugs, drugs--who has the drugs?

    PubMed

    Blair, James

    2012-01-01

    Drug diversion, although on the increase, is not the only problem involving drugs that hospital security officials should be concerned with. Growing drug shortages, offshore production, counterfeiting, and weaknesses in the drug supply chain in case of a world-wide pandemic, are even greater causes for concern, the author claims. PMID:22423518

  18. Interfacial residual thermal strain

    NASA Astrophysics Data System (ADS)

    Kasen, M.; Santoyo, R.

    A method has been developed for assessing the influence of polymer chemical composition and of processing parameters on the magnitude of residual stress developed in glass-fibre-reinforced composites subjected to various cure cycles and subsequently cooled to cryogenic temperatures. The test method was applied to nine resin types, including epoxy, vinyl ester, polyester, cyanate ester and phenolic formulations. Results suggest that polyester resin develops substantially less overall residual strain than do the other resin systems.

  19. High-throughput screening for multi-class veterinary drug residues in animal muscle using liquid chromatography/tandem mass spectrometry with on-line solid-phase extraction.

    PubMed

    Tang, Hubert Po-On; Ho, Clare; Lai, Shirley Sau-Ling

    2006-01-01

    A rapid qualitative method using on-line column-switching liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed and validated for screening 13 target veterinary drugs: four macrolides - erythromycin A, josamycin (leucomycin A3), kitasamycin (leucomycin A5), and tylosin A; six (fluoro)quinolones - ciprofloxacin, danofloxacin, enrofloxacin, flumequine, oxolinic acid, and sarafloxacin; and lincomycin, virginiamycin M1, and trimethoprim in different animal muscles. Clindamycin, norfloxacin, nalidixic acid, oleandomycin, ormetoprim, and roxithromycin were used as the internal standards. After simple deproteination and analyte extraction of muscle samples using acetonitrile, the supernatant was subjected to on-line cleanup and direct analysis by LC/MS/MS. On-line cleanup with an extraction cartridge packed with hydrophilic-hydrophobic polymer sorbent followed by fast LC using a short C18 column resulted in a total analysis cycle of 6 min for 19 drugs. This screening method considerably reduced the time and the cost for the quantitative and confirmatory analyses. The application of a control point approach was also introduced and explained. PMID:16878343

  20. Computer-aided drug designing.

    PubMed

    Gore, Mohini; Desai, Neetin S

    2014-01-01

    Computer-aided drug designing has emerged as a cost-effective and rapid tool for the discovery of newer therapeutic agents. Several algorithms have been developed to analyze protein structure and function, to identify interacting ligands, active site residues, and to study protein-ligand interactions, which can eventually lead to the identification of new drugs. In silico drug designing involves identification of the target protein which is responsible for the development of the disease under study. The three-dimensional structure of the protein can be predicted using homology modeling, while molecular docking is applied to study the interaction of a drug molecule with the protein. The best orientation of the ligand-protein docked structure which has overall minimum energy needs to be obtained. In silico methods can be used to identify potential drugs for various diseases. Thus, computer-aided drug designing has become an indispensible and integral part of the drug discovery process. PMID:24870144

  1. Drug Facts

    MedlinePlus Videos and Cool Tools

    ... Weed, Pot) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Other Drugs of Abuse What ... About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can call 1-800- ...

  2. Drug Reactions

    MedlinePlus

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as gingko and blood thinners ...

  3. Drug Resistance

    MedlinePlus

    HIV Treatment Drug Resistance (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  4. Development and model testing of anti-mortem screening methodology to predict prescribed drug withholds in heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A simple, cow-side test for the presence of drug residues in live animal fluids would provide useful information for tissue drug residue avoidance programs. This work describes adaptation and evaluation of rapid screening tests to detect drug residues in serum and urine. Medicated herd animals had...

  5. Development and model testing of anti-mortem screening methodology to predict prescribed drug withholds in heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: A simple, cow-side test for the presence of drug residues in live animal fluids would provide useful information for tissue drug residue avoidance programs. Live animal tests have the potential to allow verification that an individual animal is free of drug residues before sale for h...

  6. Close proximity gunshot residues.

    PubMed

    Thornton, J I

    1986-04-01

    Intuitively, a hand held in close proximity to a firearm at the instant of discharge will intercept a significant amount of gunshot residue, even though the hand did not actually come into contact with the weapon. There is, however, little information specifically described in the forensic science literature concerning the residue levels which might be encountered in such an instance. The present work confirms that antimony levels consistent with an individual having fired or handled a firearm may be intercepted by a hand held in close proximity. PMID:3711843

  7. CROP-RESIDUE MANAGEMENT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our agricultural production system is under increasing pressure to provide low cost, high quality food, fiber and biofuels while maintaining and preserving the environment. Increased interest in crop residues for production system sustainability is related to the recognition that the soil, water and...

  8. Drug Abuse

    MedlinePlus

    ... as drugged driving, violence, stress, and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms unborn babies and destroys families. There are different types of treatment for drug abuse. But the best is to prevent drug ...

  9. Controlled drugs.

    PubMed

    2016-05-18

    Essential facts Controlled drugs are defined and governed by the Misuse of Drugs Act 1971 and associated regulations. Examples of controlled drugs include morphine, pethidine and methadone. Since 2012, appropriately qualified nurses and midwives can prescribe controlled drugs for medical conditions within their competence. There are some exceptions when treating addiction. PMID:27191427

  10. Drug diversion

    PubMed Central

    Wood, Danielle

    2015-01-01

    SUMMARY Prescription drug diversion has significant health, legal and social implications. Deaths from misuse of prescription drugs account for a significant proportion of overdose deaths. The drugs most commonly involved are analgesics, particularly opioids, and psychoactive drugs, particularly benzodiazepines. Diverted drugs are most often sourced from a family member or friend, but are also sourced from overseas pharmacies or laboratories, or bought from drug dealers. Drug diversion can be mitigated by good prescribing practices. Systems for monitoring the prescribing and dispensing of medicines are being instituted across Australia. PMID:26648654

  11. Short communication: Macrocyclic lactone residues in butter from Brazilian markets.

    PubMed

    Macedo, Fabio; Marsico, Eliane Teixeira; Conte-Júnior, Carlos Adam; de Almeida Furtado, Leonardo; Brasil, Taila Figueredo; Pereira Netto, Annibal Duarte

    2015-06-01

    Macrocyclic lactones (ML) are commonly used in drug formulations for the treatment of parasites in cattle. In Brazil, except for drugs (or formulations) with long-term (half-life) effects, ML are registered for use in bovines. Indiscriminate use of ML may result in the presence of residues in milk and dairy products due to their lipophilic properties and thermal stability. This study applied a method of liquid chromatography with fluorimetric detection, recently developed and validated for the determination of residues of abamectin, doramectin, ivermectin, and moxidectin in butter. The method was applied to 38 samples of commercial butter purchased in the metropolitan area of Rio de Janeiro, Brazil, between June and September 2013, analyzed in triplicate. Ivermectin was detected in 89.5% of the samples, with concentrations between 0.3 and 119.4 µg/kg; 76.3% of the samples contained doramectin (0.6 to 64.7 µg/kg) and 55.2% contained abamectin (0.7 to 4.5 µg/kg). Most butter samples (76.3%) contained residues of more than 1 ML; however, no residues of moxidectin were detected. The results showed a high incidence of the presence of avermectins in butter samples. Butter is not included in the Brazilian National Plan for Control of Residues and Contaminants in Animal Products. As ML residues concentrate in lipophilic compounds, butter and other fatty dairy products should be screened for the presence of ML residues. PMID:25864054

  12. Residual stresses in material processing

    SciTech Connect

    Kozaczek, K.J.; Watkins, T.R.; Hubbard, C.R.; Wang, Xun-Li; Spooner, S.

    1994-09-01

    Material manufacturing processes often introduce residual stresses into the product. The residual stresses affect the properties of the material and often are detrimental. Therefore, the distribution and magnitude of residual stresses in the final product are usually an important factor in manufacturing process optimization or component life prediction. The present paper briefly discusses the causes of residual stresses. It then adresses the direct, nondestructive methods of residual stress measurement by X-ray and neutron diffraction. Examples are presented to demonstrate the importance of residual stress measurement in machining and joining operations.

  13. SRC Residual fuel oils

    DOEpatents

    Tewari, Krishna C.; Foster, Edward P.

    1985-01-01

    Coal solids (SRC) and distillate oils are combined to afford single-phase blends of residual oils which have utility as fuel oils substitutes. The components are combined on the basis of their respective polarities, that is, on the basis of their heteroatom content, to assure complete solubilization of SRC. The resulting composition is a fuel oil blend which retains its stability and homogeneity over the long term.

  14. Residual Neuromuscular Blockade.

    PubMed

    Plummer-Roberts, Anna L; Trost, Christina; Collins, Shawn; Hewer, Ian

    2016-02-01

    This article provides an update on residual neuromuscular blockade for nurse anesthetists. The neuromuscular junction, pharmacology for producing and reversing neuromuscular blockade, monitoring sites and methods, and patient implications relating to incomplete reversal of neuromuscular blockade are reviewed. Overall recommendations include using multiple settings when employing a peripheral nerve stimulator for monitoring return of neuromuscular function and administering pharmacologic reversal when the train-of-four ratio is below 0.9. PMID:26939390

  15. Energy from rice residues

    SciTech Connect

    Mahin, D.B.

    1990-03-01

    Developing countries produce millions of tons of rice husks and straw as a byproduct of harvesting rice. Although some of these rice residues are used for fuel or other purposes, most are burned for disposal or just dumped. However, since the mid- 1980's, industrial plants for rice residue utilization have been installed in several countries and are planned in a number of others. The report provides information on systems to produce energy from rice residues that are commercially available in the United States, Europe, and various developing countries, with an emphasis on those currently used or sold on an international level. Specifically reviewed are the use of rice husks to produce: (1) industrial process heat either directly from furnaces or by generating low pressure steam in boilers; (2) mechanical and electrical power for rice milling via steam engine systems, steam turbine/generator systems, and gasifier/engine systems; and (3) electric power for the grid. The outlook for producing energy from rice straw is also assessed. In addition, the prospects for the use of energy from husks or straw in the processing of rice bran are reviewed.

  16. Residual Viremia in Treated HIV+ Individuals.

    PubMed

    Conway, Jessica M; Perelson, Alan S

    2016-01-01

    Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. However, some residual virus remains, below the level of detection, in HIV-infected patients on ART. The source of this viremia is an area of debate: does it derive primarily from activation of infected cells in the latent reservoir, or from ongoing viral replication? Observations seem to be contradictory: there is evidence of short term evolution, implying that there must be ongoing viral replication, and viral strains should thus evolve. However, phylogenetic analyses, and rare emergent drug resistance, suggest no long-term viral evolution, implying that virus derived from activated latent cells must dominate. We use simple deterministic and stochastic models to gain insight into residual viremia dynamics in HIV-infected patients. Our modeling relies on two underlying assumptions for patients on suppressive ART: that latent cell activation drives viral dynamics and that the reproductive ratio of treated infection is less than 1. Nonetheless, the contribution of viral replication to residual viremia in patients on ART may be non-negligible. However, even if the portion of viremia attributable to viral replication is significant, our model predicts (1) that latent reservoir re-seeding remains negligible, and (2) some short-term viral evolution is permitted, but long-term evolution can still be limited: stochastic analysis of our model shows that de novo emergence of drug resistance is rare. Thus, our simple models reconcile the seemingly contradictory observations on residual viremia and, with relatively few parameters, recapitulates HIV viral dynamics observed in patients on suppressive therapy. PMID:26735135

  17. Residual Viremia in Treated HIV+ Individuals

    DOE PAGESBeta

    Conway, Jessica M.; Perelson, Alan S.

    2016-01-06

    Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. However, some residual virus remains, below the level of detection, in HIV-infected patients on ART. Furthermore, the source of this viremia is an area of debate: does it derive primarily from activation of infected cells in the latent reservoir, or from ongoing viral replication? Our observations seem to be contradictory: there is evidence of short term evolution, implying that there must be ongoing viral replication, and viral strains should thus evolve. The phylogenetic analyses, and rare emergent drug resistance, suggest no long-term viral evolution, implying that virus derived frommore » activated latent cells must dominate. We use simple deterministic and stochastic models to gain insight into residual viremia dynamics in HIV-infected patients. Our modeling relies on two underlying assumptions for patients on suppressive ART: that latent cell activation drives viral dynamics and that the reproductive ratio of treated infection is less than 1. Nonetheless, the contribution of viral replication to residual viremia in patients on ART may be non-negligible. However, even if the portion of viremia attributable to viral replication is significant, our model predicts (1) that latent reservoir re-seeding remains negligible, and (2) some short-term viral evolution is permitted, but long-term evolution can still be limited: stochastic analysis of our model shows that de novo emergence of drug resistance is rare. Thus, our simple models reconcile the seemingly contradictory observations on residual viremia and, with relatively few parameters, recapitulates HIV viral dynamics observed in patients on suppressive therapy.« less

  18. Residual Viremia in Treated HIV+ Individuals

    PubMed Central

    Conway, Jessica M.; Perelson, Alan S.

    2016-01-01

    Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. However, some residual virus remains, below the level of detection, in HIV-infected patients on ART. The source of this viremia is an area of debate: does it derive primarily from activation of infected cells in the latent reservoir, or from ongoing viral replication? Observations seem to be contradictory: there is evidence of short term evolution, implying that there must be ongoing viral replication, and viral strains should thus evolve. However, phylogenetic analyses, and rare emergent drug resistance, suggest no long-term viral evolution, implying that virus derived from activated latent cells must dominate. We use simple deterministic and stochastic models to gain insight into residual viremia dynamics in HIV-infected patients. Our modeling relies on two underlying assumptions for patients on suppressive ART: that latent cell activation drives viral dynamics and that the reproductive ratio of treated infection is less than 1. Nonetheless, the contribution of viral replication to residual viremia in patients on ART may be non-negligible. However, even if the portion of viremia attributable to viral replication is significant, our model predicts (1) that latent reservoir re-seeding remains negligible, and (2) some short-term viral evolution is permitted, but long-term evolution can still be limited: stochastic analysis of our model shows that de novo emergence of drug resistance is rare. Thus, our simple models reconcile the seemingly contradictory observations on residual viremia and, with relatively few parameters, recapitulates HIV viral dynamics observed in patients on suppressive therapy. PMID:26735135

  19. Drug Control

    ERIC Educational Resources Information Center

    Leviton, Harvey S.

    1975-01-01

    This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

  20. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-01-01

    Medicaid's Vendor Drug Program is under examination by the Texas Legislature. TMA's Physicians Medicaid Congress is seizing the opportunity to call for an administrative overhaul of a drug benefit physicians describe as unnecessarily complicated and confusing. PMID:27441421

  1. Drugged Driving

    MedlinePlus

    ... Infographics » Drugged Driving Drugged Driving Email Facebook Twitter Text Description of Infographic Top Right Figure : In 2009, ... crash than those who don't smoke. Bottom Text: Develop Social Strategies Offer to be a designated ...

  2. Generic Drugs

    MedlinePlus

    ... drugs. There are a few other differences— like color, shape, size, or taste—but they do not ... different . Brand-name drugs are often advertised by color and shape. Remember the ads for the “purple ...

  3. Drug Survey.

    ERIC Educational Resources Information Center

    Gill, Wanda E.; And Others

    Results of a survey of student perceptions of drugs and drug use that was conducted at Bowie State College are presented. Studies that have been conducted on college students' use of alcohol, marijuana, and cocaine in the last five years are reviewed, along with additional studies relating to the general population and the following drugs:…

  4. Drug Interactions

    PubMed Central

    Tong Logan, Angela; Silverman, Andrew

    2012-01-01

    One of the most clinically significant complications related to the use of pharmacotherapy is the potential for drug-drug or drug-disease interactions. The gastrointestinal system plays a large role in the pharmacokinetic profile of most medications, and many medications utilized in gastroenterology have clinically significant drug interactions. This review will discuss the impact of alterations of intestinal pH, interactions mediated by phase I hepatic metabolism enzymes and P-glycoprotein, the impact of liver disease on drug metabolism, and interactions seen with commonly utilized gastrointestinal medications. PMID:22933873

  5. The residual caries dilemma.

    PubMed

    Weerheijm, K L; Groen, H J

    1999-12-01

    Restorative dentistry is based on the assumption that bacterial infection of demineralized dentine should prompt operative intervention. One of the concepts of practical dentistry is to create a favourable environment for caries arrest with minimal operative intervention. The progress of remaining primary caries is key to any discussion of this concept. This discussion is important for the atraumatic restorative treatment (ART) approach, since the removal of all carious dentine is sometimes difficult using hand instruments only. In this paper the results of possible measures to guard against the effects of residual carious and its consequences are reviewed, in order to obtain an impression of the justification for (in)complete excavation of occlusal dentinal caries. Three types of measure are considered: isolating the caries process from the oral environment, excavating the carious dentine, and using a cariostatic filling material. Each of these measures contributes to the arrest of the caries process. However, none of these measures can arrest this process by itself. A combination of all three seems necessary. It is concluded that although residual caries does not seem to be the criterion for rerestoration, one has to strive for as complete caries removal as possible. If this cannot be fulfilled the sealing capacities of the filling material seem to be more important than its cariostatic properties. PMID:10600078

  6. 9 CFR 318.20 - Use of animal drugs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products...

  7. 9 CFR 318.20 - Use of animal drugs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products...

  8. 9 CFR 318.20 - Use of animal drugs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products...

  9. 9 CFR 318.20 - Use of animal drugs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products...

  10. 9 CFR 318.20 - Use of animal drugs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products...

  11. COPD - control drugs

    MedlinePlus

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  12. Residual gas analyzer calibration

    NASA Technical Reports Server (NTRS)

    Lilienkamp, R. H.

    1972-01-01

    A technique which employs known gas mixtures to calibrate the residual gas analyzer (RGA) is described. The mass spectra from the RGA are recorded for each gas mixture. This mass spectra data and the mixture composition data each form a matrix. From the two matrices the calibration matrix may be computed. The matrix mathematics requires the number of calibration gas mixtures be equal to or greater than the number of gases included in the calibration. This technique was evaluated using a mathematical model of an RGA to generate the mass spectra. This model included shot noise errors in the mass spectra. Errors in the gas concentrations were also included in the valuation. The effects of these errors was studied by varying their magnitudes and comparing the resulting calibrations. Several methods of evaluating an actual calibration are presented. The effects of the number of gases in then, the composition of the calibration mixture, and the number of mixtures used are discussed.

  13. Chemical modifications of therapeutic proteins induced by residual ethylene oxide.

    PubMed

    Chen, Louise; Sloey, Christopher; Zhang, Zhongqi; Bondarenko, Pavel V; Kim, Hyojin; Ren, Da; Kanapuram, Sekhar

    2015-02-01

    Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. However, specific identification of EtO adducts in proteins and the effect of residual EtO on the stability of therapeutic proteins has not been reported to date. This paper describes studies of residual EtO with two therapeutic proteins, a PEGylated form of the recombinant human granulocyte colony-stimulating factor (Peg-GCSF) and recombinant human erythropoietin (EPO) formulated with human serum albumin (HSA). Peg-GCSF was filled in an EtO sterilized delivery device and incubated at accelerated stress conditions. Glu-C peptide mapping and LC-MS analyses revealed residual EtO reacted with Peg-GCSF and resulted in EtO modifications at two methionine residues (Met-127 and Met-138). In addition, tryptic peptide mapping and LC-MS analyses revealed residual EtO in plastic vials reacted with HSA in EPO formulation at Met-328 and Cys-34. This paper details the work conducted to understand the effects of residual EtO on the chemical stability of protein therapeutics. PMID:25407640

  14. Drug Research

    NASA Technical Reports Server (NTRS)

    1989-01-01

    NBOD2, a program developed at Goddard Space Flight Center to solve equations of motion coupled N-body systems is used by E.I. DuPont de Nemours & Co. to model potential drugs as a series of elements. The program analyses the vibrational and static motions of independent components in drugs. Information generated from this process is used to design specific drugs to interact with enzymes in designated ways.

  15. Drug dependence

    MedlinePlus

    ... men References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. Kowalchuk A, Reed BC. Drug abuse. In: ...

  16. Drug abuse

    MedlinePlus

    ... abuse References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. Weiss RD. Drugs of abuse. In: Goldman ...

  17. Materials recovery from shredder residues

    SciTech Connect

    Daniels, E. J.; Jody, B. J.; Pomykala, J., Jr.

    2000-07-24

    Each year, about five (5) million ton of shredder residues are landfilled in the US. Similar quantities are landfilled in Europe and the Pacific Rim. Landfilling of these residues results in a cost to the existing recycling industry and also represents a loss of material resources that are otherwise recyclable. In this paper, the authors outline the resources recoverable from typical shredder residues and describe technology that they have developed to recover these resources.

  18. Microwave emission and crop residues

    NASA Technical Reports Server (NTRS)

    Jackson, Thomas J.; O'Neill, Peggy E.

    1991-01-01

    A series of controlled experiments were conducted to determine the significance of crop residues or stubble in estimating the emission of the underlying soil. Observations using truck-mounted L and C band passive microwave radiometers showed that for dry wheat and soybeans the dry residue caused negligible attenuation of the background emission. Green residues, with water contents typical of standing crops, did have a significant effect on the background emission. Results for these green residues also indicated that extremes in plant structure, as created using parallel and perpendicular stalk orientations, can cause very large differences in the degree of attenuation.

  19. [Drug dependence and psychotropic drugs].

    PubMed

    Giraud, M J; Lemonnier, E; Bigot, T

    1994-11-01

    Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID:7984941

  20. Antineoplastic Drugs

    NASA Astrophysics Data System (ADS)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  1. Drug Reactions

    MedlinePlus

    ... using any of these products. Some types of food may also cause adverse drug reactions. For example, grapefruit and grapefruit juice, as well as alcohol and caffeine, may affect how drugs work. Every time your doctor ... interactions with any foods or beverages. What about medicines I've used ...

  2. Drug Education.

    ERIC Educational Resources Information Center

    Sardana, Raj K.

    This autoinstructional lesson deals with the study of such drugs as marijuana and LSD, with emphasis on drug abuse. It is suggested that it can be used in science classes at the middle level of school. No prerequisites are suggested. The teacher's guide lists the behavioral objectives, the equipment needed to complete the experience and suggests…

  3. Residual effects of intranasal methamphetamine on sleep, mood, and performance

    PubMed Central

    Perez, Audrey; Kirkpatrick, Matthew G.; Gunderson, Erik W.; Marrone, Gina; Silver, Rae; Foltin, Richard W.; Hart, Carl L.

    2008-01-01

    Although intranasal methamphetamine abuse has increased, there are no published data investigating the residual effects of the drug under controlled conditions. Thus, the current study examined the residual effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Non-treatment seeking methamphetamine abusers (n = 11) completed this two-week, in-patient, within-participant, double-blind study. The study consisted of 4 two-day blocks of sessions; each block was separated by at least 24 hrs. At approximately 1000 hrs, on the first day of each block, participants received one of four intranasal methamphetamine doses (0, 12, 25, 50 mg/70 kg). Lights were turned out at 2300 hrs that evening and sleep measures were assessed. On the morning of the second day of each block, methamphetamine plasma levels, cardiovascular measures, mood, subjective reports of the previous evening's sleep, and psychomotor performance were assessed to determine residual drug effects. The larger methamphetamine doses (25 and 50 mg) markedly disrupted subjective measures of that night's sleep and some indices of next-day mood, but only the largest dose (50 mg) dose decreased objective measures of that night's sleep and increased next-day physiological measures. Methamphetamine did not produce any negative residual effects on early next-day performance. Future studies should assess methamphetamine-related residual effects following repeated doses administered over consecutive days. PMID:18078723

  4. On tide-induced lagrangian residual current and residual transport: 1. Lagrangian residual current

    USGS Publications Warehouse

    Feng, Shizuo; Cheng, Ralph T.; Pangen, Xi

    1986-01-01

    Residual currents in tidal estuaries and coastal embayments have been recognized as fundamental factors which affect the long-term transport processes. It has been pointed out by previous studies that it is more relevant to use a Lagrangian mean velocity than an Eulerian mean velocity to determine the movements of water masses. Under weakly nonlinear approximation, the parameter k, which is the ratio of the net displacement of a labeled water mass in one tidal cycle to the tidal excursion, is assumed to be small. Solutions for tides, tidal current, and residual current have been considered for two-dimensional, barotropic estuaries and coastal seas. Particular attention has been paid to the distinction between the Lagrangian and Eulerian residual currents. When k is small, the first-order Lagrangian residual is shown to be the sum of the Eulerian residual current and the Stokes drift. The Lagrangian residual drift velocity or the second-order Lagrangian residual current has been shown to be dependent on the phase of tidal current. The Lagrangian drift velocity is induced by nonlinear interactions between tides, tidal currents, and the first-order residual currents, and it takes the form of an ellipse on a hodograph plane. Several examples are given to further demonstrate the unique properties of the Lagrangian residual current.

  5. [Club drugs].

    PubMed

    Guerreiro, Diogo Frasquilho; Carmo, Ana Lisa; da Silva, Joaquim Alves; Navarro, Rita; Góis, Carlos

    2011-01-01

    Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse. PMID:22525626

  6. Results of anti-mortem screening methodology to predict prescribed drug withholding periods for flunixin and ceftiofur in heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: A simple, cow-side test for the presence of drug residues in live animals would be useful for drug residue avoidance programs. Simple inhibition tests used at slaughter do not detect some drug tolerance concentrations such as those for flunixin and ceftiofur-metabolites. This experim...

  7. Analysis of Correlations between Energy and Residue Fluctuations in Native Proteins and Determination of Specific Sites for Binding

    NASA Astrophysics Data System (ADS)

    Haliloglu, Turkan; Erman, Burak

    2009-02-01

    The Gaussian network model is used to derive the correlations between energy and residue fluctuations in native proteins. Residues are identified that respond strongly to energy fluctuations and that display correlations with the remaining residues of the protein at the highest modes. We postulate that these residues are located at specific sites for drug binding. We test the validity of this postulate on a data set of 33 structurally distinct proteins in the unbound state. Detailed results are presented for drug binding to the HIV protease.

  8. Street Drugs and Pregnancy

    MedlinePlus

    ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ...

  9. Antiretroviral drugs.

    PubMed

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one. PMID:20471318

  10. Drugged Driving

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... distance, and decrease coordination. Drivers who have used cocaine or methamphetamine can be aggressive and reckless when ...

  11. Club Drugs

    MedlinePlus

    Skip to main content En español Researchers Medical & Health Professionals Patients & ... Cold Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine Other Drugs ...

  12. Prescription Drugs

    MedlinePlus

    ... body, especially in brain areas involved in the perception of pain and pleasure. Prescription stimulants , such as ... of drug that causes changes in your mood, perceptions, and behavior can affect judgment and willingness to ...

  13. Drug Interactions

    MedlinePlus

    ... not be taken at the same time as antacids. WHAT CAUSES THE MOST INTERACTIONS WITH HIV MEDICATIONS? ... azole” Some antibiotics (names end in “mycin”) The antacid cimetidine (Tagamet) Some drugs that prevent convulsions, including ...

  14. Universality in Protein Residue Networks

    PubMed Central

    Estrada, Ernesto

    2010-01-01

    Abstract Residue networks representing 595 nonhomologous proteins are studied. These networks exhibit universal topological characteristics as they belong to the topological class of modular networks formed by several highly interconnected clusters separated by topological cavities. There are some networks that tend to deviate from this universality. These networks represent small-size proteins having <200 residues. This article explains such differences in terms of the domain structure of these proteins. On the other hand, the topological cavities characterizing proteins residue networks match very well with protein binding sites. This study investigates the effect of the cutoff value used in building the residue network. For small cutoff values, <5 Å, the cavities found are very large corresponding almost to the whole protein surface. On the contrary, for large cutoff value, >10.0 Å, only very large cavities are detected and the networks look very homogeneous. These findings are useful for practical purposes as well as for identifying protein-like complex networks. Finally, this article shows that the main topological class of residue networks is not reproduced by random networks growing according to Erdös-Rényi model or the preferential attachment method of Barabási-Albert. However, the Watts-Strogatz model reproduces very well the topological class as well as other topological properties of residue network. A more biologically appealing modification of the Watts-Strogatz model to describe residue networks is proposed. PMID:20197043

  15. Drug allergy

    PubMed Central

    Warrington, Richard

    2012-01-01

    Allergic drug reactions occur when a drug, usually a low molecular weight molecule, has the ability to stimulate an immune response. This can be done in one of two ways. The first is by binding covalently to a self-protein, to produce a haptenated molecule that can be processed and presented to the adaptive immune system to induce an immune response. Sometimes the drug itself cannot do this but a reactive breakdown product of the drug is able to bind covalently to the requisite self-protein or peptide. The second way in which drugs can stimulate an immune response is by binding non-covalently to antigen presenting or antigen recognition molecules such as the major histocompatibility complex (MHC) or the T cell receptor. This is known as the p-I or pharmacological interaction hypothesis. The drug binding in this situation is reversible and stimulation of the response may occur on first exposure, not requiring previous sensitization. There is probably a dependence on the presence of certain MHC alleles and T cell receptor structures for this type of reaction to occur. PMID:22922763

  16. Quality control of residual solvent content in polymeric microparticles.

    PubMed

    Dixit, Kalpana; Athawale, Rajani B; Singh, Sarabjit

    2015-01-01

    Organic solvents are the innate part of pharmaceutical industry, playing vital role in the bulk drug substance as well as finished product manufacturing. Even though they are used for various crucial purposes, they still lack therapeutic beneficial effect and can be toxic if present in unacceptable limits in final product. Hence, their concentration must be regulated in the final pharmaceutical formulation. With the major development in the market of polymeric microparticles in past few decades, drug product manufacturers are paying more attention towards the development of new techniques for reducing residual solvent content of microparticles. This article sheds light on the importance of removal of organic volatile impurities from the formulation and its regulatory aspects. It also highlights how residual solvent affects various physicochemical characteristics of polymeric microparticles and suggests certain solutions as per the current state of art for limiting organic solvent content in the final product. PMID:25560934

  17. Drug misuse.

    PubMed

    Waller, T

    1992-12-01

    1. Assessment by history and examination should include: a history of all drugs taken during each day for the previous 7 days (including alcohol), length of drug use and route (including the sharing of needles or syringes), the possibility of pregnancy if female, previous psychiatric history and treatment of drug misuse, social factors (including employment, family, friends, involvement in prostitution, legal problems), medical problems, including evidence of hepatitis, injection abscesses and other infections, suicide attempts, and weight loss. 2. Notification to the Chief Medical Officer of the Drug Branch of the Home Office is a legal obligation. 3. Investigations include: liver function tests (LFTs), hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis C antibody, full blood count (FBC), and urine for drug screening. Consider HIV testing if at risk but it is usually better arranged at a later stage. 4. Prescribing may be considered for a variety of drugs but objectives will differ according to drug type and individual. 5. In the case of opioid users, prescribing may be useful to stabilize their lives and to promote attendance for professional help. It may reduce high risk behaviour for contracting and spreading HIV. 6. If medication is given to opioid users, methadone mixture 1 mg/ml given once a day is the prescription of choice. Dispensing should be on a daily basis and the blue prescription form FP10 (MDA) allows the chemist to dispense daily for up to 14 days. A maximum ceiling of 100 mg methadone/day should not be exceeded. The initial dose will depend on the amount of opioid consumed in the previous week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1345155

  18. Drugs@FDA: FDA Approved Drug Products

    MedlinePlus

    ... Cosmetics Tobacco Products Drugs@FDA: FDA Approved Drug Products FDA Home Drug Databases Drugs@FDA - FAQ | Instructions | ... 6332) Contact FDA For Government For Press Combination Products Advisory Committees Science & Research Regulatory Information Safety Emergency ...

  19. Americium recovery from reduction residues

    DOEpatents

    Conner, W.V.; Proctor, S.G.

    1973-12-25

    A process for separation and recovery of americium values from container or bomb'' reduction residues comprising dissolving the residues in a suitable acid, adjusting the hydrogen ion concentration to a desired level by adding a base, precipitating the americium as americium oxalate by adding oxalic acid, digesting the solution, separating the precipitate, and thereafter calcining the americium oxalate precipitate to form americium oxide. (Official Gazette)

  20. Detecting ketamine in beverage residues: Application in date rape detection.

    PubMed

    Albright, Jessica A; Stevens, Sarah A; Beussman, Douglas J

    2012-05-01

    Ketamine can be used to facilitate date-rape when unknowingly spiked into a victim's beverage. If a biological sample is not available from the victim, the beverage container might be the only remaining source of forensic evidence. We present a rapid, simple analysis method for the detection of ketamine in wet or dry beverage residues based on liquid chromatography-mass spectrometry (LC-MS). Wet residues consist of the final few drops (<1 ml) in a container while dry residues are the remains once all liquid has evaporated. By using LC-MS, which readily handles aqueous samples, often no derivatization or sample extraction is needed, thus reducing analysis time and lab technician involvement. Tandem mass spectrometry (MS/MS) provides an enhancement in both selectivity and sensitivity. We have studied a range of beverages and determined limits of detection between 1.2 × 10-3 and 1.3 × 10-4 mg/ml, compared to 0.21-0.85 mg/ml used in most date-rape scenarios. This paper represents the first published report of using LC-MS/MS for the analysis of beverage residues for the presence of a date-rape drug. This method could replace the current gas chromatography-mass spectrometry (GC-MS) methods and provide a faster, more selective method for the analysis of date-rape drugs, requiring virtually no sample preparation. PMID:22114065

  1. Effect of cooking on enrofloxacin residues in chicken tissue.

    PubMed

    Lolo, M; Pedreira, S; Miranda, J M; Vázquez, B I; Franco, C M; Cepeda, A; Fente, C

    2006-10-01

    The aim of this study was to determine the effect of different cooking processes (microwaving, roasting, boiling, grilling and frying) on naturally incurred enrofloxacin residues in chicken muscle. Enrofloxacin and its metabolite, ciprofloxacin, were analysed using a validated LC-MS method with limits of detection (LOD) and quantification (LOQ), respectively, of 2 and 5 ng g-1 quinolones in muscle samples. The method was shown to be linear over the range 5-500 ng g-1. Mean intra-day relative standard deviation (RSD) at a concentration of 50 ng g-1 (n = 6) was 6%; inter-day RSD was 12%. A recovery study demonstrated that 65-101%, of the drug and metabolite could be recovered from the tissue. The RSD with naturally incurred roasted chicken breast was 9.18% at a concentration of 11 +/- 1.01 ng g-1 (n = 6). In water, enrofloxacin remained stable for 3 h when heated at 100 degrees C. It was concluded that residue data from raw tissue are valid for estimation of consumer exposure to this drug, as well as the ADI calculations because cooking procedures did not affect enrofloxacin residues, which remained stable during heating. However, there was an apparent decrease in quinolone concentration in tissue because some was lost by exudation into the liquid used for cooking. Conversely, for a cooking procedure with water loss, there was an apparent increase in residue concentration. PMID:16982520

  2. A review of coccidiostats and the analysis of their residues in meat and other food.

    PubMed

    Clarke, Lesa; Fodey, Terence L; Crooks, Steven R H; Moloney, Mary; O'Mahony, John; Delahaut, Philippe; O'Kennedy, Richard; Danaher, Martin

    2014-07-01

    Coccidiostats are used in the control of protozoan infections in different food producing animals. They are most widely used as feed additives in intensively reared species such as pigs and poultry to maintain animal health and in some cases enhance feed conversion. However, a number of these drugs are used in the control of infections in beef and lamb production. Coccidiostat residues have been frequently reported in meat and eggs in a number of countries since the late 1990s. This has prompted increased research and surveillance of coccidiostat residues in food. This paper reviews the various coccidiostat agents used in animal production, including their chemical properties, mode of action and activity. Legislation concerning coccidiostats, limits for residues in food, monitoring and occurrence of residues in food is discussed. Methods for residue determination in food, including screening and physicochemical methods are discussed in depth. The paper concludes with a synopsis of the current state of coccidiostat residue analysis and future perspectives. PMID:24534603

  3. Drug Allergy.

    PubMed

    Waheed, Abdul; Hill, Tiffany; Dhawan, Nidhi

    2016-09-01

    An adverse drug reaction relates to an undesired response to administration of a drug. Type A reactions are common and are predictable to administration, dose response, or interaction with other medications. Type B reactions are uncommon with occurrences that are not predictable. Appropriate diagnosis, classification, and entry into the chart are important to avoid future problems. The diagnosis is made with careful history, physical examination, and possibly allergy testing. It is recommended that help from allergy immunology specialists should be sought where necessary and that routine prescription of Epi pen should be given to patients with multiple allergy syndromes. PMID:27545730

  4. [Ureter drugs].

    PubMed

    Raynal, G; Bellan, J; Saint, F; Tillou, X; Petit, J

    2008-03-01

    Many improvements have been made recently in the field of the ureteral smooth muscle pharmacology. After a brief summary on physiological basis, we review what is known about effects on ureter of different drugs class. In a second part, we review clinical applications for renal colic analgesia, calculi expulsive medical therapy, ESWL adjuvant treatment and preoperative treatment before retrograde access. There are now sufficient data on NSAID and alpha-blockers. beta-agonists, especially for beta3 selective ones, and topical drugs before retrograde access are interesting and should be further evaluated. PMID:18472067

  5. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Recent developments on new anti-HIV agents and drugs for opportunistic infections are highlighted. Information is provided on the infusion inhibitor T-20; DuPont's second generation non-nukes, DPC 961 and DPC 963; Papirine (PEN203) for the human papilloma virus; Sporanox for treating fungal infections; and the antiretroviral protein, lysozyme. In addition, information is given on a plant found in the Bolivian rainforest that may contain compounds to prevent HIV infection by blocking the enzyme, integrase. Other promising new drugs addressed at the 6th Conference on Retroviruses and Opportunistic Infections are listed in a table. Contact information for US clinical trials is provided. PMID:11366758

  6. DISSOLUTION OF NEPTUNIUM OXIDE RESIDUES

    SciTech Connect

    Kyser, E

    2009-01-12

    This report describes the development of a dissolution flowsheet for neptunium (Np) oxide (NpO{sub 2}) residues (i.e., various NpO{sub 2} sources, HB-Line glovebox sweepings, and Savannah River National Laboratory (SRNL) thermogravimetric analysis samples). Samples of each type of materials proposed for processing were dissolved in a closed laboratory apparatus and the rate and total quantity of off-gas were measured. Samples of the off-gas were also analyzed. The quantity and type of solids remaining (when visible) were determined after post-dissolution filtration of the solution. Recommended conditions for dissolution of the NpO{sub 2} residues are: Solution Matrix and Loading: {approx}50 g Np/L (750 g Np in 15 L of dissolver solution), using 8 M nitric acid (HNO{sub 3}), 0.025 M potassium fluoride (KF) at greater than 100 C for at least 3 hours. Off-gas: Analysis of the off-gas indicated nitric oxide (NO), nitrogen dioxide (NO{sub 2}) and nitrous oxide (N{sub 2}O) as the only identified components. No hydrogen (H{sub 2}) was detected. The molar ratio of off-gas produced per mole of Np dissolved ranged from 0.25 to 0.4 moles of gas per mole of Np dissolved. A peak off-gas rate of {approx}0.1 scfm/kg bulk oxide was observed. Residual Solids: Pure NpO{sub 2} dissolved with little or no residue with the proposed flowsheet but the NpCo and both sweepings samples left visible solid residue after dissolution. For the NpCo and Part II Sweepings samples the residue amounted to {approx}1% of the initial material, but for the Part I Sweepings sample, the residue amounted to {approx}8 % of the initial material. These residues contained primarily aluminum (Al) and silicon (Si) compounds that did not completely dissolve under the flowsheet conditions. The residues from both sweepings samples contained minor amounts of plutonium (Pu) particles. Overall, the undissolved Np and Pu particles in the residues were a very small fraction of the total solids.

  7. Residual stresses in welded plates

    NASA Technical Reports Server (NTRS)

    Bernstein, Edward L.

    1994-01-01

    The purpose of this project was to develop a simple model which could be used to study residual stress. The mechanism that results in residual stresses in the welding process starts with the deposition of molten weld metal which heats the immediately adjacent material. After solidification of weld material, normal thermal shrinkage is resisted by the adjacent, cooler material. When the thermal strain exceeds the elastic strain corresponding to the yield point stress, the stress level is limited by this value, which decreases with increasing temperature. Cooling then causes elastic unloading which is restrained by the adjoining material. Permanent plastic strain occurs, and tension is caused in the region immediately adjacent to the weld material. Compression arises in the metal farther from the weld in order to maintain overall static equilibrium. Subsequent repair welds may add to the level of residual stresses. The level of residual stress is related to the onset of fracture during welding. Thus, it is of great importance to be able to predict the level of residual stresses remaining after a weld procedure, and to determine the factors, such as weld speed, temperature, direction, and number of passes, which may affect the magnitude of remaining residual stress. It was hoped to use traditional analytical modeling techniques so that it would be easier to comprehend the effect of these variables on the resulting stress. This approach was chosen in place of finite element methods so as to facilitate the understanding of the physical processes. The accuracy of the results was checked with some existing experimental studies giving residual stress levels found from x-ray diffraction measurements.

  8. Residual deformations in ocular tissues

    PubMed Central

    Wang, Ruoya; Raykin, Julia; Gleason, Rudolph L.; Ethier, C. Ross

    2015-01-01

    Residual deformations strongly influence the local biomechanical environment in a number of connective tissues. The sclera is known to be biomechanically important in healthy and diseased eyes, such as in glaucoma. Here, we study the residual deformations of the sclera, as well as the adjacent choroid and retina. Using freshly harvested porcine eyes, we developed two approaches of quantifying residual deformations in the spherically shaped tissues of interest. The first consisted of punching discs from the posterior wall of the eye and quantifying the changes in the area and eccentricity of these samples. The second consisted of cutting a ring from the equatorial sclera and making stress-relieving cuts in it. Measurements of curvature were made before and after the stress-relieving cuts. Using the first approach, we observed a 42% areal contraction of the choroid, but only modest contractions of the sclera and retina. The observed contractions were asymmetric. In the second approach, we observed an opening of the scleral rings (approx. 10% decrease in curvature). We conclude that residual bending deformations are present in the sclera, which we speculate may be due to radially heterogeneous growth and remodelling of the tissue during normal development. Further, residual areal deformations present in the choroid may be due to the network of elastic fibres in this tissue and residual deformations in the constituent vascular bed. Future studies of ocular biomechanics should attempt to include effects of these residual deformations into mechanical models in order to gain a better understanding of the biomechanics of the ocular wall. PMID:25740853

  9. Drug Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Drug resistance refers to both intrinsic and acquired abilities of cells or organisms to become insensitive or refractory to chemotherapeutic intervention. The advent of antibiotics is considered one of the most important medicinal developments in human history, which has led to significantly reduce...

  10. Antineoplastic Drugs.

    ERIC Educational Resources Information Center

    Morris, Sara; Michael, Nancy, Ed.

    This module on antineoplastic drugs is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  11. Club Drugs

    MedlinePlus

    ... Drug Gamma-hydroxybutyrate (GHB), also known as G, Liquid Ecstasy, and Soap Ketamine, also known as Special K, K, Vitamin K, and Jet Rohypnol, also known as Roofies Methamphetamine, also known as Speed, Ice, Chalk, Meth, Crystal, Crank, and Glass Lysergic Acid Diethylamide (LSD), also ...

  12. Total residue analysis of swabs by ion mobility spectrometry.

    PubMed

    Strege, Mark A

    2009-06-01

    Ion mobility spectrometry (IMS) is a technique attractive for use within the pharmaceutical industry for at-line determination of residues on swabs taken from the surfaces of manufacturing equipment for the purposes of cleaning validation or verification. In this study, the development of a novel IMS method to provide a measurement of total residue present on a swab is described. The technique is based upon quantitation of charged atmospheric gas reactant ion consumption (RIC) within the instrument as a direct measure of the mass of total ionizable residue. Coupled with the conventional analysis of the active pharmaceutical ingredient within a single 2 min analysis, RIC determination provided the benefit of a single measure representative of the presence of multiple residue components or unknown components. To account for differences in response between components of a model drug product (Cymbalta) and its associated cleaning agents, a strategy was proposed to determine a "worst case" total residue test result based on RIC. A limitation of the IMS method was its incompatibility with cleaners containing a high concentration of inorganic components. The methodology provided a range from 5-50 microg per 25 cm(2) surface area and acceptable analyte recovery (50-100%). PMID:19476393

  13. 77 FR 72254 - New Animal Drugs; Updating Tolerances for Residues of New Animal Drugs in Food

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-05

    ... Federal Regulations (21 CFR part 556) (40 FR 13802 at 13942, March 27, 1975). The part 556 regulations... must be non-detectable or below the limit of detection of the approved regulatory method (67 FR...

  14. Dry fermentation of agricultural residues

    NASA Astrophysics Data System (ADS)

    Jewell, W. J.; Chandler, J. A.; Dellorto, S.; Fanfoni, K. J.; Fast, S.; Jackson, D.; Kabrick, R. M.

    1981-09-01

    A dry fermentation process is discussed which converts agricultural residues to methane, using the residues in their as produced state. The process appears to simplify and enhance the possibilities for using crop residues as an energy source. The major process variables investigated include temperature, the amount and type of inoculum, buffer requirements, compaction, and pretreatment to control the initial available organic components that create pH problems. A pilot-scale reactor operation on corn stover at a temperature of 550 C, with 25 percent initial total solids, a seed-to-feed ratio of 2.5 percent, and a buffer-to-feed ratio of 8 percent achieved 33 percent total volatile solids destruction in 60 days. Volumetric biogas yields from this unit were greater than 1 vol/vol day for 12 days, and greater than 0.5 vol/vol day for 32 days, at a substrate density of 169 kg/m (3).

  15. Chemistry of combined residual chlorination

    SciTech Connect

    Leao, S.F.; Selleck, R.E.

    1982-01-01

    The decay of the combined chlorine residual was investigated in this work. Recent concerns about the formation of undesirable compounds such as chloroform with free residual chlorination have focused attention on the alternative use of combined residual chlorination. This work investigates the applicability of reactions proposed to describe the transformations and decay of the combined residual with time. Sodium hypochlorite was added to buffered solutions of ammonia with the chlorine residual being monitored over periods extending up to 10 days. The reaction was studied at four initial concentrations of hypochlorite of 100, 50, 25 and 10 mg/L as Cl/sub 2/ with molar application ratios of chlorine to ammonia, defined herein as M ratios, of 0.90, 0.50, 0.25 and 0.05 at each hypochlorite dose. Sixty-eight experiments were conducted at the pH of 6.6 and 7.2. The conclusions are: (1) in the absence of free chlorine, the concentration of NH/sub 3/ does not seem to affect the rate of disappearance of the residual other than through the formation of NHCl/sub 2/ by NH/sub 2/Cl hydrolysis; (2) the reaction between NHCl/sub 2/ and NH/sub 4//sup +/ to form NH/sub 2/Cl is either much slower than reported by Gray et. al. or the mechanism is different with a rate limiting step not involving NH/sub 3/ or NH/sub 4//sup +/; (3) a redox reaction in addition to the first-order decomposition of NHCl/sub 2/ appears necessary. Model simulation results indicated that a reaction of the type NH/sub 2/Cl + NHCl/sub 2/ ..-->.. P added to the first-order NHCl/sub 2/ decomposition can explain the results observed except at the higher chlorine doses.

  16. Therapeutic drug monitoring: antiarrhythmic drugs

    PubMed Central

    Campbell, T J; Williams, K M

    2001-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents. PMID:11564050

  17. 40 CFR 1065.705 - Residual and intermediate residual fuel.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... specifications for fuels meeting the definition of residual fuel in 40 CFR 80.2, including fuels marketed as... 991.0 1010.0 ISO 3675 or ISO 12185 (see also ISO 8217). Kinematic viscosity at 50 °C, max cSt 30.0...

  18. 75 FR 24394 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... medicated article was voluntarily withdrawn (60 FR 37651, July 21, 1995) and approved conditions of use for... NADA 45-738, were removed (60 FR 39847, July 21, 1995). At this time, the tolerances for residues of... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 556 and 558 Animal Drugs, Feeds, and...

  19. Collection of sugarcane crop residue for energy

    SciTech Connect

    Eiland, B.R.; Clayton, J.E.

    1982-12-01

    Crop residue left after sugarcane harvesting was recovered using a forage harvester and a large round baler. The quantity, bulk density and moisture content of the crop residue was determined in four fields. Crop residue from 7 ha was burned in boilers at a sugar mill. Samples of this residue were tested by a laboratory and compared to sugarcane bagasse.

  20. Residual Structures in Latent Growth Curve Modeling

    ERIC Educational Resources Information Center

    Grimm, Kevin J.; Widaman, Keith F.

    2010-01-01

    Several alternatives are available for specifying the residual structure in latent growth curve modeling. Two specifications involve uncorrelated residuals and represent the most commonly used residual structures. The first, building on repeated measures analysis of variance and common specifications in multilevel models, forces residual variances…

  1. Caspase-3 binds diverse P4 residues in peptides as revealed by crystallography and structural modeling.

    SciTech Connect

    Fang, Bin; Fu, Guoxing; Agniswamy, Johnson; Harrison, Robert W.; Weber, Irene T.

    2009-03-31

    Caspase-3 recognition of various P4 residues in its numerous protein substrates was investigated by crystallography, kinetics, and calculations on model complexes. Asp is the most frequent P4 residue in peptide substrates, although a wide variety of P4 residues are found in the cellular proteins cleaved by caspase-3. The binding of peptidic inhibitors with hydrophobic P4 residues, or no P4 residue, is illustrated by crystal structures of caspase-3 complexes with Ac-IEPD-Cho, Ac-WEHD-Cho, Ac-YVAD-Cho, and Boc-D(OMe)-Fmk at resolutions of 1.9-2.6 {angstrom}. The P4 residues formed favorable hydrophobic interactions in two separate hydrophobic regions of the binding site. The side chains of P4 Ile and Tyr form hydrophobic interactions with caspase-3 residues Trp206 and Trp214 within a non-polar pocket of the S4 subsite, while P4 Trp interacts with Phe250 and Phe252 that can also form the S5 subsite. These interactions of hydrophobic P4 residues are distinct from those for polar P4 Asp, which indicates the adaptability of caspase-3 for binding diverse P4 residues. The predicted trends in peptide binding from molecular models had high correlation with experimental values for peptide inhibitors. Analysis of structural models for the binding of 20 different amino acids at P4 in the aldehyde peptide Ac-XEVD-Cho suggested that the majority of hydrophilic P4 residues interact with Phe250, while hydrophobic residues interact with Trp206, Phe250, and Trp214. Overall, the S4 pocket of caspase-3 exhibits flexible adaptation for different residues and the new structures and models, especially for hydrophobic P4 residues, will be helpful for the design of caspase-3 based drugs.

  2. IMPROVED TECHNIQUES FOR RESIDUAL OZONE

    EPA Science Inventory

    Eight analytical methods for the determination of residual ozone in water are evaluated. Four are iodometric methods based on the reduction of ozone by iodide ion: the iodometric method, the amperometric method, the arsenic (III) back titration method, and the N, N-diethyl-p-phen...

  3. Leptogenesis and residual CP symmetry

    NASA Astrophysics Data System (ADS)

    Chen, Peng; Ding, Gui-Jun; King, Stephen F.

    2016-03-01

    We discuss flavour dependent leptogenesis in the framework of lepton flavour models based on discrete flavour and CP symmetries applied to the type-I seesaw model. Working in the flavour basis, we analyse the case of two general residual CP symmetries in the neutrino sector, which corresponds to all possible semi-direct models based on a preserved Z 2 in the neutrino sector, together with a CP symmetry, which constrains the PMNS matrix up to a single free parameter which may be fixed by the reactor angle. We systematically study and classify this case for all possible residual CP symmetries, and show that the R-matrix is tightly constrained up to a single free parameter, with only certain forms being consistent with successful leptogenesis, leading to possible connections between leptogenesis and PMNS parameters. The formalism is completely general in the sense that the two residual CP symmetries could result from any high energy discrete flavour theory which respects any CP symmetry. As a simple example, we apply the formalism to a high energy S 4 flavour symmetry with a generalized CP symmetry, broken to two residual CP symmetries in the neutrino sector, recovering familiar results for PMNS predictions, together with new results for flavour dependent leptogenesis.

  4. Pyrotechnic reaction residue particle analysis.

    PubMed

    Kosanke, Kenneth L; Dujay, Richard C; Kosanke, Bonnie J

    2006-03-01

    Pyrotechnic reaction residue particle (PRRP) production, sampling and analysis are all very similar to that for primer gunshot residue. In both cases, the preferred method of analysis uses scanning electron microscopy to locate suspect particles and then uses energy dispersive x-ray spectroscopy to characterize the particle's constituent chemical elements. There are relatively few times when standard micro-analytical chemistry performed on pyrotechnic residues may not provide sufficient information for forensic investigators. However, on those occasions, PRRP analysis provides a greatly improved ability to discriminate between materials of pyrotechnic origin and other unrelated substances also present. The greater specificity of PRRP analysis is the result of its analyzing a large number of individual micron-sized particles, rather than producing only a single integrated result such as produced using standard micro-analytical chemistry. For example, PRRP analyses are used to demonstrate its ability to successfully (1) discriminate between pyrotechnic residues and unrelated background contamination, (2) identify that two different pyrotechnic compositions had previously been exploded within the same device, and (3) establish the chronology of an incident involving two separate and closely occurring explosions. PMID:16566762

  5. Asthma - control drugs

    MedlinePlus

    Asthma - inhaled corticosteroids; Asthma - long-acting beta-agonists; Asthma - leukotriene modifiers; Asthma - cromolyn; Bronchial asthma-control drugs; Wheezing - control drugs; Reactive airway disease - control drugs

  6. Drug Rash (Unclassified Drug Eruption) in Children

    MedlinePlus

    ... rash and rashes clinical tools newsletter | contact Share | Drug Eruption, Unclassified (Pediatric) A parent's guide to condition ... lesions coming together into larger lesions typical of drug rashes (eruptions). Overview A drug eruption, also known ...

  7. Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

    PubMed Central

    Guarnieri, Michael; Tyler, Betty M.; DeTolla, Louis; Zhao, Ming; Kobrin, Barry

    2014-01-01

    Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs. PMID:24459402

  8. [Emergent drugs (I): smart drugs].

    PubMed

    Burillo-Putze, G; Díaz, B Climent; Pazos, J L Echarte; Mas, P Munné; Miró, O; Puiguriguer, J; Dargan, P

    2011-01-01

    In recent years, a series of new drugs, known as smart drugs or legal highs, have gaining in popularity. They are easily obtainable through online shops. This is happening amongst younger segments of the population and is associated with recreational consumption, at weekends. In general, they are synthetic derivatives of natural products. There has been hardly any clinical research into them and they are not detectable in hospital laboratories. Three of these products, BZP (1- benzylpiperazine), mefedrone (4-methylmethcathinone) and Spice are probably the most widely used in Europe. The first two are consumed as an alternative to ecstasy and cocaine and are characterized by their producing a clinical profile of a sympathetic mimetic type; on occasion, they have serious consequences, with convulsions and even death. Spice (a mixture of herbs with synthetic cannabinoids such as JWH-018, JWH-073 and CP 47497-C8) is giving rise to profiles of dependence and schizophrenia. Although the emergent drugs have an aura of safety, there is an increasing amount of experience on their secondary effects. PMID:21904408

  9. Therapeutic Drug Monitoring

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  10. Drug Plan Coverage Rules

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    ... works with other insurance Find health & drug plans Drug plan coverage rules Note Call your Medicare drug ... shingles vaccine) when medically necessary to prevent illness. Drugs you get in hospital outpatient settings In most ...