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Drug Testing (drug + testing)

Distribution by Scientific Domains

Medical Sciences	46%
Chemistry	43%
Life Sciences	10%

Selected Abstracts

Current Awareness in Drug Testing and Analysis

DRUG TESTING AND ANALYSIS, Issue 4 2010
Article first published online: 1 APR 2010
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of drug testing and analysis. Each bibliography is divided into 18 sections: 1 Reviews; 2 Sports doping - General; 3 Steroids; 4 Peptides; 5 Diuretics; 6 CNS agents; 7 Equine; 8 Recreational drugs - General; 9 Stimulants; 10 Hallucinogens; 11 Narcotics; 12 Forensics; 13 Alcohol; 14 Tobacco; 15 Homeland security; 16 Workplace; 17 Product authenticity; 18 Techniques. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]

Current Awareness in Drug Testing and Analysis

DRUG TESTING AND ANALYSIS, Issue 9-10 2009
Article first published online: 22 DEC 200
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of drug testing and analysis. Each bibliography is divided into 18 sections: 1 Reviews; 2 Sports doping - General; 3 Steroids; 4 Peptides; 5 Diuretics; 6 CNS agents; 7 Equine; 8 Recreational drugs - General; 9 Stimulants; 10 Hallucinogens; 11 Narcotics; 12 Forensics; 13 Alcohol; 14 Tobacco; 15 Homeland security; 16 Workplace; 17 Product authenticity; 18 Techniques. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]

Current Awareness in Drug Testing and Analysis

DRUG TESTING AND ANALYSIS, Issue 6 2009
Article first published online: 7 OCT 200
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of drug testing and analysis. Each bibliography is divided into 18 sections: 1 Reviews; 2 Sports doping - General; 3 Steroids; 4 Peptides; 5 Diuretics; 6 CNS agents; 7 Equine; 8 Recreational drugs - General; 9 Stimulants; 10 Hallucinogens; 11 Narcotics; 12 Forensics; 13 Alcohol; 14 Tobacco; 15 Homeland security; 16 Workplace; 17 Product authenticity; 18 Techniques. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]

Hair Analysis Versus Conventional Methods of Drug Testing in Substance Abusers Seeking Organ Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010
D. L. Haller
As substance abusers need to demonstrate abstinence prior to transplant, valid/reliable drug tests are needed. Patients may deny use, fearing surgery will be delayed. Breath, blood and urine tests have brief detection windows that allow patients to evade detection. Routine laboratory tests do not include all substances of abuse. Hair analysis overcomes these barriers, increasing the likelihood that active users will be identified. This study compared results for alcohol, opioids and cocaine based on 445 self-report, breath, urine and hair samples from 42 patients who had been denied a transplant due to recent substance abuse. Compared to hair toxicology, sensitivity for conventional drug tests was moderate for cocaine and opioids, but poor for alcohol. Of positive hair tests, only half were corroborated through other tests. In contrast, specificity was high across tests and substances, with positive findings from conventional tests confirmed through hair toxicology. Based on a 90-day detection window for hair analysis, two negative tests suggest 6 months of continuous abstinence. Hair testing should be considered as an alternative approach for monitoring substance use in the transplant population, either as a routine procedure or when the veracity of findings from conventional tests is in doubt. [source]

Accelerating botulism therapeutic product development in the Department of Defense,

DRUG DEVELOPMENT RESEARCH, Issue 4 2009
Andrea M. Stahl
Abstract Coordinated small-molecule drug discovery research efforts for the treatment of botulism by the public sector, especially the U.S. Department of Defense (DoD) and Department of Health and Human Services (DHHS), began in the 1990s and represent a significant resource investment. Organization of an effective botulism therapeutic drug program, however, presents formidable technical and logistical challenges. Seven distinct BoNT serotypes are known, each representing a different target. Moreover, BoNT exerts its action inside peripheral cholinergic neurons, and some serotypes may persist functionally within nerve cells for weeks or months. Clinical botulism occurs infrequently, and the effectiveness of prolonged mechanical ventilation to treat poisoning further limits experimental drug testing. The efficacy of experimental compounds must be extrapolated from disparate cell- or tissue-based or rodent models. Numerous compounds with moderate efficacy in experimental laboratory assays have been reported, but may not possess the necessary safety, efficacy, and pharmacokinetic profile to support therapeutic development. To mitigate these challenges, we propose product development tools to assist in management of the BoNT portfolio and to clearly define the desired therapeutic product. Establishing a target product profile (TPP) is proposed to guide public sector managers toward critical aspects of the desired therapeutic product. Additional product development tools to assist in shaping research portfolios and to inform decisions regarding lead candidates to pursue are also discussed. Product development tools that facilitate the characterization of the ideal therapeutic product, and assist in the maintenance of a robust portfolio, will ameliorate the inherent financial risk in drug development for treating BoNT intoxication. Drug Dev Res 70:303,326, 2009. Published 2009 Wiley-Liss, Inc. [source]

Current Awareness in Drug Testing and Analysis

Application of FAIMS to anabolic androgenic steroids in sport drug testing

DRUG TESTING AND ANALYSIS, Issue 11-12 2009
Sven Guddat
Abstract Mass spectrometric identification of anabolic androgenic steroids challenges standard doping-control methods. To reveal a doping offence the presence of prohibited anabolic androgenic steroids at trace levels in the picogram-per-millilitre range must be confirmed as reliable. Human urine samples containing epitrenbolone, metandienone metabolite (17, -hydroxymethyl-17,-methyl-18-norandrost-1,4,13-trien-3-one), stanozolol, 16,-hydroxystanozolol and 4,-hydroxystanozolol were analysed using LC-FAIMS-MS/MS. These substances are prohibited in sport according to World Anti-Doping Agency (WADA) regulations. Glucuronides were hydrolysed and prepared by liquid-liquid extraction. Excellent recovery and precision were obtained for all compounds. Linear calibration results for epitrenbolone and metandienone metabolite were obtained and concentration information could be determined in the ranges of reliable response between 750,1200 and 100,600 pg/mL, respectively. Limits of detection were estimated at 25 pg/mL (stanozolol), 50 pg/mL (metandienone metabolite, 16,-hydroxystanozolol), 100 pg/mL (4,-hydroxystanozolol) and 500 pg/mL (epitrenbolone). The assay was applied to doping-control samples. For all analytes, LC-FAIMS-MS/MS resulted in excellent interference removal, which effectively extends the post-dose detection time. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Current Awareness in Drug Testing and Analysis

LC-MS: a powerful tool in workplace drug testing

DRUG TESTING AND ANALYSIS, Issue 3 2009
E. Gallardo
Abstract Workplace drug testing is a well-established application of forensic toxicology and it aims to reduce workplace accidents caused by affected workers. Several classes of abused substances may be involved, such as alcohol, amphetamines, cannabis, cocaine, opiates and also prescription drugs, such as benzodiazepines. The use of alternative biological specimens such as hair, oral fluid or sweat in workplace drug testing presents several advantages over urinalysis,mainly the fact that sample collection can be performed easily without infringing on the examinee's privacy, so the subject is more likely to perform the test. However, drugs are usually present in these alternative specimens at low concentrations and the amount of sample available for analysis is small. The use of highly sensitive techniques is therefore necessary. In fact, the successful interface of liquid chromatography with mass spectrometry (LC-MS) has brought a new light into bioanalytical and forensic sciences as it allows the detection of drugs and metabolites at concentrations that are difficult to analyse using the more commonly adopted GC-MS based techniques. This paper will discuss the importance of LC-MS in supporting workplace drug-testing programmes. The combination of LC-MS with innovative instrumentation such as triple quadrupoles, ion traps and time-of-flight mass spectrometers will also be focused. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Testing for cannabis in the work-place: a review of the evidence

ADDICTION, Issue 3 2010
Scott Macdonald
ABSTRACT Background Urinalysis testing in the work-place has been adopted widely by employers in the United States to deter employee drug use and promote ,drug-free' work-places. In other countries, such as Canada, testing is focused more narrowly on identifying employees whose drug use puts the safety of others at risk. Aims We review 20 years of published literature on questions relevant to the objectives of work-place drug testing (WPDT), with a special emphasis on cannabis, the most commonly detected drug. Results We conclude (i) that the acute effects of smoking cannabis impair performance for a period of about 4 hours; (ii) long-term heavy use of cannabis can impair cognitive ability, but it is not clear that heavy cannabis users represent a meaningful job safety risk unless using before work or on the job; (iii) urine tests have poor validity and low sensitivity to detect employees who represent a safety risk; (iv) drug testing is related to reductions in the prevalence of cannabis positive tests among employees, but this might not translate into fewer cannabis users; and (v) urinalysis has not been shown to have a meaningful impact on job injury/accident rates. Conclusions Urinalysis testing is not recommended as a diagnostic tool to identify employees who represent a job safety risk from cannabis use. Blood testing for active tetrahydrocannabinol (THC) can be considered by employers who wish to identify employees whose performance may be impaired by their cannabis use. [source]

Addiction research centres and the nurturing of creativity: The Centre for Addictions Research of British Columbia, Canada

ADDICTION, Issue 2 2010
Tim Stockwell
ABSTRACT The Centre for Addictions Research of British Columbia (CARBC) was established as a multi-campus and multi-disciplinary research centre administered by the University of Victoria (UVic) in late 2003. Its core funding is provided from interest payments on an endowment of CAD$10.55 million. It is supported by a commitment to seven faculty appointments in various departments at UVic. The Centre has two offices, an administration and research office in Victoria and a knowledge exchange unit in Vancouver. The two offices are collaborating on the implementation of CARBC's first 5-year plan which seeks to build capacity in British Columbia for integrated multi-disciplinary research and knowledge exchange in the areas substance use, addictions and harm reduction. Present challenges include losses to the endowment caused by the 2008/2009 economic crisis and difficulties negotiating faculty positions with the university administration. Despite these hurdles, to date each year has seen increased capacity for the Centre in terms of affiliated scientists, funding and staffing as well as output in terms of published reports, electronic resources and impacts on policy and practice. Areas of special research interest include: drug testing in the work-place, epidemiological monitoring, substance use and injury, pricing and taxation policies, privatization of liquor monopolies, polysubstance use, health determinants of indigenous peoples, street-involved youth and other vulnerable populations at risk of substance use problems. Further information about the Centre and its activities can be found on http://www.carbc.ca. [source]

The spatial epidemiology of cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) use: a demonstration using a population measure of community drug load derived from municipal wastewater

ADDICTION, Issue 11 2009
Caleb J. Banta-Green
ABSTRACT Aims To determine the utility of community-wide drug testing with wastewater samples as a population measure of community drug use and to test the hypothesis that the association with urbanicity would vary for three different stimulant drugs of abuse. Design and participants Single-day samples were obtained from a convenience sample of 96 municipalities representing 65% of the population of the State of Oregon. Measurements Chemical analysis of 24-hour composite influent samples for benzoylecgonine (BZE, a cocaine metabolite), methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). The distribution of community index drug loads accounting for total wastewater flow (i.e. dilution) and population are reported. Findings The distribution of wastewater-derived drug index loads was found to correspond with expected epidemiological drug patterns. Index loads of BZE were significantly higher in urban areas and below detection in many rural areas. Conversely, methamphetamine was present in all municipalities, with no significant differences in index loads by urbanicity. MDMA was at quantifiable levels in fewer than half the communities, with a significant trend towards higher index loads in more urban areas. Conclusion This demonstration provides the first evidence of the utility of wastewater-derived community drug loads for spatial analyses. Such data have the potential to improve dramatically the measurement of the true level and distribution of a range of drugs. Drug index load data provide information for all people in a community and are potentially applicable to a much larger proportion of the total population than existing measures. [source]

Employment-based abstinence reinforcement as a maintenance intervention for the treatment of cocaine dependence: a randomized controlled trial

ADDICTION, Issue 9 2009
Anthony DeFulio
ABSTRACT Context Due to the chronic nature of cocaine dependence, long-term maintenance treatments may be required to sustain abstinence. Abstinence reinforcement is among the most effective means of initiating cocaine abstinence. Practical and effective means of maintaining abstinence reinforcement programs over time are needed. Objective To determine whether employment-based abstinence reinforcement can be an effective long-term maintenance intervention for cocaine dependence. Design Participants (n = 128) were enrolled in a 6-month job skills training and abstinence initiation program. Participants who initiated abstinence, attended regularly and developed needed job skills during the first 6 months were hired as operators in a data entry business and assigned randomly to an employment-only (control, n = 24) or abstinence-contingent employment (n = 27) group. Setting A non-profit data entry business. Participants Unemployed welfare recipients who used cocaine persistently while enrolled in methadone treatment in Baltimore. Intervention Abstinence-contingent employment participants received 1 year of employment-based contingency management, in which access to employment was contingent upon provision of drug-free urine samples under routine and then random drug testing. If a participant provided drug-positive urine or failed to provide a mandatory sample, then that participant received a temporary reduction in pay and could not work until urinalysis confirmed recent abstinence. Main outcome measure Cocaine-negative urine samples at monthly assessments across 1 year of employment. Results During the 1 year of employment, abstinence-contingent employment participants provided significantly more cocaine-negative urine samples than employment-only participants [79.3% and 50.7%, respectively; P = 0.004, odds ratio (OR) = 3.73, 95% confidence interval (CI) = 1.60,8.69]. Conclusions Employment-based abstinence reinforcement that includes random drug testing is effective as a long-term maintenance intervention, and is among the most promising treatments for drug dependence. Work-places could serve as therapeutic agents in the treatment of drug dependence by arranging long-term employment-based contingency management programs. [source]

The Pharmacokinetics of Antiepileptic Drugs in Rats: Consequences for Maintaining Effective Drug Levels during Prolonged Drug Administration in Rat Models of Epilepsy

EPILEPSIA, Issue 7 2007
Wolfgang Löscher
Summary:, Rodent models of chronic epilepsy with spontaneous recurrent seizures likely represent the closest parallel to the human condition. Such models may be best suited for therapy discovery for pharmacoresistant epilepsy and for antiepileptogenic or disease-modifying therapeutics. However, the use of such rodent models for therapy discovery creates problems with regard to maintaining effective drug levels throughout a prolonged testing period. This is particularly due to the fact that rodents such as rats and mice eliminate most drugs much more rapidly than humans. Thus, knowledge about elimination rate of a test drug in a laboratory species is essential for development of a treatment paradigm that allows maintaining adequate drug levels in the system over the period of treatment. Currently, the most popular models of epilepsy with spontaneous seizures are poststatus epilepticus models of temporal lobe epilepsy in rats. Such models are both used for studies on antiepileptogenesis and drug resistance. For validation of these models, current antiepileptic drugs (AEDs) have to be used. In this article, the elimination rates of these AEDs and their effective plasma levels in rats are reviewed as a guide for developing treatment protocols for chronic drug testing. The advantages and disadvantages of several technologies for drug delivery are discussed, and some examples for calculation of adequate treatment protocols are given. As shown in this review, because of the rapid elimination of most AEDs in rats, it is no trivial task to maintain effective steady-state AED levels in the plasma throughout the day over multiple days to ensure that there will be adequate levels in the system for the purpose of the experiment. However, the use of an adequate dosing regimen that is based on elimination rate is an absolute prerequisite when using rat models for discovery of new antiepileptogenic therapies or therapies for pharmacoresistant epilepsy, because otherwise such models may lead to erroneous conclusions about drug efficacy. [source]

Disability payments, drug use and representative payees: an analysis of the relationships

ADDICTION, Issue 7 2003
James A. Swartz
ABSTRACT Aims This study attempted to determine: if US federal cash disability payments increase the use of cocaine or opiates among those requalifying for supplemental security income (SSI) disability benefits compared with those who lost benefits; if drug use peaks at the beginning of the month after the receipt of the disability cash disbursement; and if money management by representative payees of requalifying SSI recipients suppresses drug use. Design A multi-site, prospective, 2 year longitudinal design was used with follow-up interviews conducted every 6 months. Urine samples were collected at the final three follow-up interviews. Setting Data were collected in Chicago, IL, Los Angeles, CA, and Seattle, WA, USA. Participants This study used a randomly selected sample of 740 former recipients of SSI who had received disability benefits for drug addiction and alcoholism (DA&A) in 1996, were between the ages of 21 and 59 years, had not received concurrent social security disability insurance and provided testable urine samples and complete self-report data for at least one follow-up interview. Measurements Independent variables included demographics, SSI status at follow-up, representative payee status, drug treatment participation and income. Time of drug testing was operationalized as the first 10 days of the month versus the last 20,21 days based on when the urine sample was collected. The dependent variables were cocaine and opiate use, determined by urinalysis results. Findings Participants were 28% more likely to test positive for cocaine use in the first 10 days of the month than later in the month. This effect was general across all subjects and was not restricted to those receiving SSI benefits. No such effect was found for opiate use. Receiving SSI benefits did not increase cocaine or opiate use generally, nor did having a representative payee suppress use. Conclusions The findings do not support the contentions that federal cash benefits appreciably increase drug use or that representative payees discourage use, at least when use is defined dichotomously. The ,check effect' for cocaine use appears to be general and not confined to those receiving federal cash benefits. The lack of a ,check effect' for opiate use is probably the result of the difference between a relatively steady state of opiate use associated with addiction and a binge pattern of cocaine use triggered by suddenly flush resources. [source]

Comparative Pharmacology of Guinea Pig Cardiac Myocyte and Cloned hERG (IKr) Channel

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2004
CHRISTINA DAVIE Ph.D.
Introduction: This study used whole-cell, patch clamp techniques on isolated guinea pig ventricular myocytes and HEK293 cells expressing cloned human ether-a-go-go-related gene (hERG) to examine the action of drugs causing QT interval prolongation and torsades de pointes (TdP) in man. Similarities and important differences in drug actions on cardiac myocytes and cloned hERG IKr channels were established. Qualitative actions of the drugs on cardiac myocytes corresponded with results obtained from Purkinje fibers and measurement of QT interval prolongation in animal and human telemetry studies. Methods and Results: Adult guinea pig ventricular myocytes were isolated by enzymatic digestion. Cells were continuously perfused with Tyrode's solution at 33,35°C. Recordings were made using the whole-cell, patch clamp technique. Action potentials (APs) were elicited under current clamp. Voltage clamp was used to study the effect of drugs on IKr (rapidly activating delayed rectifier potassium current), INa (sodium current), and ICa (L-type calcium current). Dofetilide increased the myocyte action potential duration (APD) in a concentration-dependent manner, with a pIC50 of 7.3. Dofetilide 1 ,M elicited early afterdepolarizations (EADs) but had little affect on ICa or INa. E-4031 increased APD in a concentration-dependent manner, with a pIC50 of 7.2. In contrast, 10 ,M loratadine, desloratadine, and cetirizine had little effect on APD or IKr. Interestingly, cisapride displayed a biphasic effect on myocyte APD and inhibited ICa at 1 ,M. Even at this high concentration, cisapride did not elicit EADs. A number of AstraZeneca compounds were tested on cardiac myocytes, revealing a mixture of drug actions that were not observed in hERG currents in HEK293 cells. One compound, particularly AR-C0X, was a potent blocker of myocyte AP (pIC50 of 8.4). AR-C0X also elicited EADs in cardiac myocytes. The potencies of the same set of drugs on the cloned hERG channel also were assessed. The pIC50 values for dofetilide, E-4031, terfenadine, loratadine, desloratadine, and cetirizine were 6.8, 7.1, 7.3, 5.1, 5.2, and <4, respectively. Elevation of temperature from 22 to 35°C significantly enhanced the current kinetics and amplitudes of hERG currents and resulted in approximately fivefold increase in E-4031 potency. Conclusion: Our study demonstrates the advantages of cardiac myocytes over heterologously expressed hERG channels in predicting QT interval prolongation and TdP in man. The potencies of some drugs in cardiac myocytes were similar to hERG, but only myocytes were able to detect important changes in APD characteristics and display EADs predictive of arrhythmia development. We observed similar qualitative drug profiles in cardiac myocytes, dog Purkinje fibers, and animal and human telemetry studies. Therefore, isolated native cardiac myocytes are a better predictor of drug-induced QT prolongation and TdP than heterologously expressed hERG channels. Isolated cardiac myocytes, when used with high-throughput patch clamp instruments, may have an important role in screening potential cardiotoxic compounds in the early phase of drug discovery. This would significantly reduce the attrition rate of drugs entering preclinical and/or clinical development. The current kinetics and amplitudes of the cloned hERG channel were profoundly affected by temperature, significantly altering the potency of one drug (E-4031). This finding cautions against routine drug testing at room temperature compared to physiologic temperature when using the cloned hERG channel. [source]

Vesicle traffic through intercellular bridges in DU 145 human prostate cancer cells

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2004
Cristina Vidulescu
Abstract We detected cell-to-cell communication via intercellular bridges in DU 145 human prostate cancer cells by fluorescence microscopy. Since DU 145 cells have deficient gap junctions, intercellular bridges may have a prominent role in the transfer of chemical signals between these cells. In culture, DU 145 cells are contiguous over several cell diameters through filopodial extensions, and directly communicate with adjacent cells across intercellular bridges. These structures range from 100 nm to 5 ,m in diameter, and from a few microns to at least 50,100 ,m in length. Time-lapse imagery revealed that (1) filopodia rapidly move at a rate of microns per minute to contact neighboring cells and (2) intercellular bridges are conduits for transport of membrane vesicles (1,3 ,m in diameter) between adjacent cells. Immunofluorescence detected alpha-tubulin in intercellular bridges and filopodia, indicative of microtubule bundles, greater than a micron in diameter. The functional meaning, interrelationship of these membrane extensions are discussed, along with the significance of these findings for other culture systems such as stem cells. Potential applications of this work include the development of anticancer therapies that target intercellular communication and controlling formation of cancer spheroids for drug testing. [source]

Emerging drugs: mechanism of action, mass spectrometry and doping control analysis

JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 4 2009
Mario Thevis
Abstract The number of compounds and doping methods in sports is in a state of constant flux. In addition to ,traditional' doping agents, such as anabolic androgenic steroids or erythropoietin, new therapeutics and emerging drugs have considerable potential for misuse in elite sport. Such compounds are commonly based on new chemical structures, and the mechanisms underlying their modes of action represent new therapeutic approaches arising from recent advances in medical research; therefore, sports drug testing procedures need to be continuously modified and complementary methods developed, preferably based on mass spectrometry, to enable comprehensive doping controls. This tutorial not only discusses emerging drugs that can be categorized as anabolic agents (selective androgen receptor modulators, SARMs), gene doping [hypoxia-inducible factor stabilizers, peroxisome-proliferator-activated receptor (PPAR),-agonists] and erythropoietin-mimetics (Hematide) but also compounds with potentially performance-enhancing properties that are not classified in the current list of the World Anti-Doping Agency. Compounds such as ryanodine-calstabin-complex modulators (benzothiazepines) are included, their mass spectrometric properties discussed, and current approaches in sports drug testing outlined. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Use of a point-of-care urine drug test in a dog to assist in diagnosing barbiturate toxicosis secondary to ingestion of a euthanized carcass

JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 3 2009
DACVA, DACVECC, Vicki L. Campbell DVM
Abstract Objective , To describe a case of barbiturate toxicosis in a dog secondary to ingestion of a previously buried euthanized goat carcass and to discuss the utility of urine drug testing in diagnosing barbiturate toxicosis. Case Summary , A 6-year-old neutered male Border Collie was presented to a university veterinary teaching hospital for evaluation of ataxia and acute collapse. Past pertinent history included Addison's disease that had been managed for 1 year. A companion dog was seen 12 hours earlier chewing on the partially decomposed head of a goat that had been euthanized 47 days previously and buried on the owner's property. The dog was laterally recumbent, unresponsive to stimuli, and hypothermic on physical examination. Initial blood work revealed hyponatremia and hyperkalemia, with a Na/K ratio of 18.5. The dog was volume resuscitated and received an injection of dexamethasone sodium phosphate due to a suspected Addisonian crisis. Despite this treatment, the dog remained laterally recumbent and unresponsive to stimuli. A urine drug screen was performed and was positive for barbiturates. A diagnosis of barbiturate toxicosis secondary to ingestion of a euthanized goat carcass was made. The dog was treated supportively over 12 hours with IV fluids and activated charcoal. The dog was able to walk 11 hours after presentation and was subsequently discharged from the hospital. New or Unique Information Provided , Urine drug testing is a fast, easy, and point-of-care test that may be useful in dogs to assist in the diagnosis of barbiturate intoxication. Proper disposal of euthanized animals is necessary to prevent toxicosis and possible death of companion animals and wildlife. [source]

In vitro biotransformation of anabolic steroids in canines

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2000
Williams
Forensic drug testing of anabolic steroids in racing animals is required because of the potential for steroid abuse. Often when the metabolic products of an administered compound have not been identified, the analysis and verification of the administered compound is difficult. The objective of this study was to qualitatively identify the in vitro phase I biotransformation products of anabolic steroids that have a high potential for abuse in canines. The investigated steroids included testosterone, methyltestosterone, mibolerone and boldenone. Steroid biotransformation products were generated using beagle liver microsomes and analysed by high performance liquid chromatography (HPLC)/mass spectrometry (MS) with an electrospray ionization source. Characterization of steroid metabolites was based on HPLC retention, UV and mass spectra. The major testosterone metabolites were identified as androstenedione and 6,- and 16,-hydroxytestosterone. 6,-Hydroxymethyltestosterone was identified as a major metabolite in the methyltestosterone microsomal incubations. Several mibolerone metabolites were identified as monohydroxylated mibolerones as well as an oxidized mibolerone metabolite. Boldenone metabolites were identified as monohydroxylated boldenones, oxidized boldenone, and testosterone. This information should assist in the determination of anabolic steroid use in canines through the correlation of the urinary metabolites to the administered drug. [source]

Mass spectrometric determination of insulins and their degradation products in sports drug testing

MASS SPECTROMETRY REVIEWS, Issue 1 2008
Mario Thevis
Abstract Insulins' anabolic and anti-catabolic properties have supposedly led to its misuse in sport. Hence, doping control assays were developed to allow the unequivocal identification of synthetic insulin analogs and metabolic products derived from human insulin and its artificial counterparts in urine and plasma specimens. Analyses were based on immunoaffinity purification and subsequent characterization of target analytes by top-down sequencing-based approaches, which were conducted with hybrid tandem mass spectrometers that consisted of either quadrupole-linear ion trap or linear ion trap-orbitrap analyzers. Diagnostic product ions and analytical strategies are presented and discussed in light of the need to unambiguously identify misused drugs in urine and plasma specimens for doping control. © 2007 Wiley Periodicals, Inc., Mass Spec Rev 27:35,50, 2008 [source]

Interpreting Urine Drug Tests: Prevalence of Morphine Metabolism to Hydromorphone in Chronic Pain Patients Treated with Morphine

PAIN MEDICINE, Issue 7 2008
Ajay D. Wasan MD
ABSTRACT Objective., Pain medicine practitioners frequently use urine drug testing (UDT) to monitor adherence to opioid therapy. It can be difficult to interpret a result as normal or abnormal in relation to which opioid compounds are expected to be found in the urine. We investigated whether hydromorphone may be a metabolite of morphine normally appearing in UDT of patients prescribed morphine. Design., This is a retrospective case-control study of urine toxicology results in pain patients taking only morphine. Inclusion criteria included urine results positive for morphine only (controls) or morphine and hydromorphone (cases). Demographic and medical history variables, and any history of aberrant drug behavior were recorded and related to the presence or absence of hydromorphone in the urine. Results., Hydromorphone was present in 21 of 32 cases (66%), none of whom had a history of aberrant drug behavior. Positive cases occurred more frequently in women, in those taking higher daily doses of morphine, and in those with higher urine morphine concentrations (P < 0.05). Only morphine urine concentration was a significant predictor of the hydromorphone metabolite in a logistic regression model (P < 0.05). Conclusions., Hydromorphone is likely a minor metabolite of morphine, normally appearing in the UDT of patients taking morphine. This finding assists in determining whether a UDT result is normal or abnormal, and subsequently whether a patient is compliant with opioid therapy. This observation should be confirmed by a prospective study in a controlled environment. Variables such as gender, morphine dose, morphine urine concentration, and genetic determinants of morphine metabolism should be investigated further. [source]

Comprehensive plasma-screening for known and unknown substances in doping controls

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 8 2010
Andreas Thomas
Occasionally, doping analysis has been recognized as a competitive challenge between cheating sportsmen and the analytical capabilities of testing laboratories. Both have made immense progress during the last decades, but obviously the athletes have the questionable benefit of frequently being able to switch to new, unknown and untested compounds to enhance their performance. Thus, as analytical counteraction and for effective drug testing, a complementary approach to classical targeted methods is required in order to implement a comprehensive screening procedure for known and unknown xenobiotics. The present study provides a new analytical strategy to circumvent the targeted character of classical doping controls without losing the required sensitivity and specificity. Using 50,µL of plasma only, the method potentially identifies illicit drugs in low ng/mL concentrations. Plasma provides the biological fluid with the circulating, unmodified xenobiotics; thus the identification of unknown compounds is facilitated. After a simple protein precipitation, liquid chromatographic separation and subsequent detection by means of high resolution/high accuracy orbitrap mass spectrometry, the procedure enables the determination of numerous compounds from different classes prohibited by the World Anti-Doping Agency (WADA). A new hyphenated mass spectrometry technology was employed without precursor ion selection for higher collision energy dissociation (HCD) fragmentation experiments. Thus the mass spectra contained all the desired information to identify unknown substances retrospectively. The method was validated for 32 selected model compounds for qualitative purposes considering the parameters specificity, selectivity, limit of detection (<0.1,10,ng/mL), precision (9,28%), robustness, linearity, ion suppression and recovery (80,112%). In addition to the identification of unknown compounds, the plasma samples were simultaneously screened for known prohibited targets. Copyright © 2010 John Wiley & Sons, Ltd. [source]

Mass spectrometric identification and characterization of a new long-term metabolite of metandienone in human urine

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 15 2006
Wilhelm Schänzer
Anabolic-androgenic steroids are some of the most frequently detected drugs in amateur and professional sports. Doping control laboratories have developed numerous assays enabling the determination of administered drugs and/or their metabolic products that allow retrospectives with respect to pharmacokinetics and excretion profiles of steroids and their metabolites. A new metabolite generated from metandienone has been identified as 18-nor-17, -hydroxymethyl,17, -methyl-androst-1,4,13-trien-3-one in excretion study urine samples providing a valuable tool for the long-term detection of metandienone abuse by athletes in sports drug testing. The metabolite was characterized using gas chromatography/(tandem) mass spectrometry, liquid chromatography/tandem mass spectrometry and liquid chromatography/high-resolution/high-accuracy (tandem) mass spectrometry by characteristic fragmentation patterns representing the intact 3-keto-1,4-diene structure in combination with typical product ions substantiating the proposed C/D-ring structure of the steroid metabolite. In addition, structure confirmation was obtained by the analysis of excretion study urine specimens obtained after administration of 17-CD3 -labeled metandienone providing the deuterated analogue to the newly identified metabolite. 18-Nor-17, -hydroxymethyl,17, -methyl-androst-1,4,13-trien-3-one was determined in metandienone administration study urine specimens up to 19 days after application of a single dose of 5,mg, hence providing an extended detection period compared with commonly employed strategies. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Hypoxia enhances proliferation of mouse embryonic stem cell-derived neural stem cells

BIOTECHNOLOGY & BIOENGINEERING, Issue 2 2010
Carlos A.V. Rodrigues
Abstract Neural stem (NS) cells can provide a source of material with potential applications for neural drug testing, developmental studies, or novel treatments for neurodegenerative diseases. Herein, the ex vivo expansion of a model system of mouse embryonic stem (mES) cell-derived NS cells was characterized and optimized, cells being cultivated under adherent conditions. Culture was first optimized in terms of initial cell plating density and oxygen concentration, known to strongly influence brain-derived NS cells. To this end, the growth of cells cultured under hypoxic (2%, 5%, and 10% O2) and normoxic (20% O2) conditions was compared. The results showed that 2,5% oxygen, without affecting multipotency, led to fold increase values in total cell number about twice higher than observed under 20% oxygen (20-fold vs. 10-fold, respectively) this effect being more pronounced when cells were plated at low density. With an optimal cell density of 104,cells/cm2, the maximum growth rates were 1.9,day,1 under hypoxia versus 1.7,day,1 under normoxia. Cell division kinetics analysis by flow cytometry based on PKH67 tracking showed that when cultured in hypoxia, cells are at least one divisional generation ahead compared to normoxia. In terms of cell cycle, a larger population in a quiescent G0 phase was observed in normoxic conditions. The optimization of NS cell culture performed here represents an important step toward the generation of a large number of neural cells from a reduced initial population, envisaging the potential application of these cells in multiple settings. Biotechnol. Bioeng. 2010;106: 260,270. © 2009 Wiley Periodicals, Inc. [source]

In vitro liver model using microfabricated scaffolds in a modular bioreactor

BIOTECHNOLOGY JOURNAL, Issue 2 2010
Bruna Vinci
Abstract Hepatocyte function on 3-D microfabricated polymer scaffolds realised with the pressure-activated microsyringe was tested under static and dynamic conditions. The dynamic cell culture was obtained using the multicompartment modular bioreactor system. Hepatocyte cell density, glucose consumption, and albumin secretion rate were measured daily over a week. Cells seeded on scaffolds showed an increase in cell density compared with monolayer controls. Moreover, in dynamic culture, cell metabolic function increased three times in comparison with static monolayer cultures. These results suggest that cell density and cell-cell interactions are mediated by the architecture of the substrate, while the endogenous biochemical functions are regulated by a sustainable supply of nutrients and interstitial-like flow. Thus, a combination of 3-D scaffolds and dynamic flow conditions are both important for the development of a hepatic tissue model for applications in drug testing and regenerative medicine. [source]

Passaging Protocols for Mammalian Neural Stem Cells in Suspension Bioreactors

BIOTECHNOLOGY PROGRESS, Issue 2 2002
Arindom Sen
Mammalian neural stem cells (NSC) offer great promise as therapeutic agents for the treatment of central nervous system disorders. As a consequence of the large numbers of cells that will be needed for drug testing and transplantation studies, it is necessary to develop protocols for the large-scale expansion of mammalian NSC. Neural stem cells and early progenitor cells can be expanded in vitro as aggregates in controlled bioreactors using carefully designed media. The first objective of this study was to determine if it is possible to maintain a population of murine neural stem and progenitor cells as aggregates in suspension culture bioreactors over extended periods of time. We discovered that serial passaging of a mixture of aggregates sizes resulted in high viabilities, high viable cell densities, and good control of aggregate diameter. When the NSC aggregates were serially subcultured three times without mechanical dissociation, a total multiplication ratio of 2.9 × 103 was achieved over a period of 12 days, whereas the aggregate size was controlled (mean diameter less than 150 ,m) below levels at which necrosis would occur. Moreover, cell densities of 1.0 × 106 cells/mL were repeatedly achieved in batch culture with viabilities exceeding 80%. The second objective was to examine the proliferative potential of single cells shed from the surface of these aggregates. We found that the single cells, when subcultured, retained the capacity to generate new aggregates, gave rise to cultures with high viable cell densities and were able to differentiate into all of the primary cell phenotypes in the central nervous system. [source]