Journal of analytical toxicology (J ANAL TOXICOL )

Description

Journal of Analytical Toxicology (JAT) is the international source for practical clinical/forensic applications for isolating, identifying and quantitating potentially toxic substances. The Journal of Analytical Toxicology (JAT) is an international publication devoted to the timely dissemination of scientific communications concerning the isolation, identification, and quantitation of drugs and other substances. Since its inception in 1977, JAT has striven to present state-of-the art techniques to address current issues in toxicology. The peer-review process provided by the distinguished members of the Editorial Advisory Board ensures the high quality and integrity of JAT articles. Timely presentation of the latest scientific developments is ensured through "Technical Notes", "Case Reports", and "Letters to the Editor". Worldwide readership of JAT includes toxicologists, pathologists, chemists, clinicians, researchers, and educators working in medical examiner and law enforcement laboratories, hospitals, university, and independent analytical laboratories, as well as the drug manufacturing industry. With an emphasis on practical application, JAT articles introduce improved and novel techniques for use in clinical, forensic, workplace, sports testing (doping), and other toxicology laboratories. Articles describe newly developed methods in immunoassay testing, gas chromatography, liquid chromatography, mass spectrometry, atomic absorption spectrometry, solid- and liquid-phase extraction techniques, and other analytical approaches. The methods published in JAT describe the chemical analysis of therapeutic drugs, drugs of abuse, pharmaceuticals, pesticides, industrial chemicals, and environmental toxins. The methods are generally applicable to the fields of forensic science, therapeutic drug monitoring, drug abuse testing, clinical and forensic toxicology, industrial hygiene.

  • Impact factor
    2.11
  • 5-year impact
    1.76
  • Cited half-life
    8.60
  • Immediacy index
    0.43
  • Eigenfactor
    0.00
  • Article influence
    0.47
  • Website
    Journal of Analytical Toxicology (JAT) website
  • Other titles
    Journal of analytical toxicology, JAT
  • ISSN
    1945-2403
  • OCLC
    2942106
  • Material type
    Periodical
  • Document type
    Journal / Magazine / Newspaper

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Increased cannabis potency has renewed concerns that secondhand exposure to cannabis smoke can produce positive drug tests. A systematic study was conducted of smoke exposure on drug-free participants. Six experienced cannabis users smoked cannabis cigarettes (5.3% THC in Session 1 and 11.3% THC in Sessions 2 and 3) in a sealed chamber. Six non-smokers were seated with smokers in an alternating manner. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Non-smoking participant specimens (collected 0-34 h) were analyzed with four immunoassays at different cutoff concentrations (20, 50, 75 and 100 ng/mL) and by GC-MS (LOQ = 0.75 ng/mL). No presumptive positives occurred for non-smokers at 100 and 75 ng/mL; a single positive occurred at 50 ng/mL; and multiple positives occurred at 20 ng/mL. Maximum THCCOOH concentrations by GC-MS for non-smokers ranged from 1.3 to 57.5 ng/mL. THCCOOH concentrations generally increased with THC potency, but room ventilation substantially reduced exposure levels. These results demonstrate that extreme cannabis smoke exposure can produce positive urine tests at commonly utilized cutoff concentrations. However, positive tests are likely to be rare, limited to the hours immediately post-exposure, and occur only under environmental circumstances where exposure is obvious.
    Journal of analytical toxicology 10/2014;
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    ABSTRACT: A sensitive screening method based on fast liquid chromatography tandem mass-spectrometry (RSLC-MS-MS) has shown the feasibility of separation and detection of low concentration β-lyase metabolites of sulfur mustard and of nerve agent phosphonic acids in urine. The analysis of these compounds is of interest because they are specific metabolites of the chemical warfare agents (CWAs), sulfur mustard (HD), sarin (GB), soman (GD), VX and Russian VX (RVX). The 'dilute-and-shoot' RSLC-MS-MS method provides a sensitive and direct approach for determining CWA exposure in non-extracted non-derivatized samples from urine. Chromatographic separation of the metabolites was achieved using a reverse phase column with gradient mobile phases consisting of 0.5% formic acid in water and acetonitrile. Identification and quantification of species were achieved using electrospray ionization-tandem mass-spectrometry monitoring two precursor-to-product ion transitions for each compound. The method demonstrates linearity over at least two orders of magnitude and had detection limits of 0.5 ng/mL in urine.
    Journal of analytical toxicology 10/2014;
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    ABSTRACT: The combination of Herba Ephedrae (Mahuang in Chinese) and Radix Aconiti Lateralis (Fuzi in Chinese) is a classical preparation in traditional Chinese medicine and used for treating colds and rheumatic arthralgia. However, herbal medicines containing ephedrines and Aconitum alkaloids are strictly regulated because of the potential for adverse effects on the cardiovascular system and the central nervous system. We aimed to investigate the pharmacokinetics of 11 alkaloids in the Mahuang-Fuzi combination and single-herb extracts after oral administration in rats. The alkaloids were norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, methylephedrine, aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine. Simultaneous determination of the alkaloids, including two pairs of diastereomers, was achieved in 14.5 min by a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method. The separation was performed on a Zorbax SB-Aq column (100 mm × 2.1 mm, 3.5 μm) at a flow rate of 0.3 mL/min using acetonitrile-0.1% formic acid aqueous solution as the mobile phase. The validated method demonstrated adequate sensitivity, selectivity and process efficiency for the quantitative analysis of complex herbal components. Compared with single-herb extracts, alkaloids in plasma (except methylephedrine, benzoylmesaconine and benzoylhypaconine) showed slower elimination (the mean residence time or half-life was longer), although the maximum plasma concentration and area under the plasma concentration curve values decreased. Accumulation may occur with continuous drug intake. These results suggest that drug monitoring may be essential for the safe use of the Mahuang-Fuzi combination.
    Journal of analytical toxicology 10/2014;
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    ABSTRACT: A multidrug fatality involving sumatriptan is reported. Sumatriptan is a tryptamine derivative that acts at 5-HT1B/1D receptors and is used for the treatment of migraines. The decedent was a 21-year-old white female found dead in bed by her spouse. No signs of physical trauma were observed and a large number of prescription medications were discovered at the scene. Toxicological analysis of the central blood revealed sumatriptan at a concentration of 1.03 mg/L. Following therapeutic dosing guidelines, sumatriptan concentrations do not exceed 0.095 mg/L. Sumatriptan was isolated by solid-phase extraction and analyzed using liquid chromatography-tandem mass spectrometry in multiple reaction monitoring mode. A tissue distribution study was completed with the following concentrations measured: 0.61 mg/L in femoral blood, 0.56 mg/L in iliac blood, 5.01 mg/L in urine, 0.51 mg/kg in liver, 3.66 mg/kg in kidney, 0.09 mg/kg in heart, 0.32 mg/kg in spleen, 0.01 mg/kg in brain, 15.99 mg/kg in lung and 78.54 mg/45 mL in the stomach contents. Carisoprodol, meprobamate, fluoxetine, doxylamine, orphenadrine, dextromethorphan and hydroxyzine were also present in the blood at the following concentrations: 3.35, 2.36, 0.63, 0.19, 0.06, 0.55 and 0.16 mg/L. The medical examiner ruled the cause of death as acute mixed drug toxicity and the manner of death as accident.
    Journal of analytical toxicology 10/2014;
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    ABSTRACT: A novel liquid chromatography-tandem mass spectrometry method was validated for identification and quantification of diazepam, flunitrazepam and metabolites in reinforced clostridial medium (RCM), a complex matrix used to provide the nutrients required for bacterial growth. The method was designed for subsequent use in the investigation of gastrointestinal bacteria as a potential source of postmortem alteration of drugs of abuse and respective metabolite concentrations. A literature review yielded no experimental means or model for the extraction and analysis of samples from RCM or similar bacterial medium. Development and validation of a new experimental method were therefore critical. In future work, this method could be adapted and extended to similar organic compounds of interest. The calibration curves extended from 0.100 to 500 ng/mL. Analyte recoveries ranged from 95 to 119% and matrix effects from 97 to 119%. Bias was ≤±17.6%, within-run precision ≤12.2%, and between-run precision ≤11.7% across all concentration levels. The limits of detection and quantitation ranged from 0.100 to 1 ng/mL. Dilution integrity was maintained for 1:2 and 1:5 dilutions. Analytes were stable through two freeze-thaw cycles and processed samples for 48 h. Method robustness was evaluated by changes in buffer composition and column temperature as well as samples prepared by an alternate analyst.
    Journal of analytical toxicology 10/2014;
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    ABSTRACT: Chemical straightening, also known as a relaxer, is ubiquitously used among African American women to obtain straighter hair compared with their natural tresses. This study focused on the stability of drugs of abuse in hair after a single application of the relaxer. Commercially available 'Lye' or 'No-Lye' chemical straightening products (Silk Elements™) were applied in vitro to drug-fortified hair (standard reference materials (SRM) 2379 and 2380) and hairs clipped from established drug users. Target analytes (cocaine (COC), benzoylecgonine (BZE), cocaethylene (CE), phencyclidine and tetrahydrocannabinol) were isolated using solid-phase extraction and then analyzed with isotope dilution gas chromatography-mass spectrometry with selective ion monitoring. After either treatment, drug concentrations were significantly (P < 0.05) decreased in both the SRM sample and the hair from authentic abusers. In the SRM groups, 6-67% of the original concentration remained after a single chemical treatment. Similarly, only 5-30% of the original concentration remained in authentic drug hairs that had formerly tested positive for COC, BZE and CE.
    Journal of analytical toxicology 10/2014;
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    ABSTRACT: Urine drug testing (UDT) is an emerging standard of care in the evaluation and treatment of chronic non-cancer pain patients with opioid analgesics. UDT may be used both to verify adherence with the opioid analgesic regimen and to monitor abstinence from non-prescribed or illicit controlled substances. In the former scenario, it is vital to determine whether the drug is present in the urine, even at low concentrations, because failure to detect the drug may lead to accusations of opioid abuse or diversion. Opiate immunoassays typically are developed to detect morphine and are most sensitive to morphine and codeine. Although many opiate immunoassays also detect hydrocodone (HC) and/or hydromorphone (HM), sensitivities for these analytes are often much lower, increasing the possibility of negative screening results when the drug is present in the urine. We selected 112 urine specimens from patients who had been prescribed HC or hydromorphone but were presumptive negative by the Roche Online DAT Opiate II™ urine drug screening assay, which is calibrated to 300 ng/mL morphine. Using a GC/MS confirmatory method with a detection limit of 50 ng/mL both for HC and for HM, one or both of these opiates were detected in 81 (72.3%) of the urine specimens. Examination of the raw data from these presumptive negative opiate screens revealed that, in many cases, the turbidity signal was greater than the signal obtained for the negative control, but less than the signal for the 300 ng/mL (morphine) threshold calibrator. A receiver operating characteristic curve generated for the reciprocal of the ratio of turbidity measurements in the patient specimens and negative (drug-free) controls, against the presence or absence of HC and/or HM by confirmatory analyses, produced an area under the curve of 0.910. We conclude that this opiate immunoassay has sufficient sensitivity to detect HC and/or HM in some urine specimens that screen presumptive negative for these commonly prescribed opiates at the established threshold.
    Journal of analytical toxicology 10/2014;
  • Journal of analytical toxicology 10/2014;
  • Journal of analytical toxicology 10/2014;
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    ABSTRACT: Only trace amounts of parent benzodiazepines are present in urine following extensive metabolism and conjugation. Thus, hydrolysis of glucuronides is necessary for improved detection. Enzyme hydrolysis is preferred to retain identification specificity, but can be costly and time-consuming. The assessment of a novel recombinant β-glucuronidase for rapid hydrolysis in benzodiazepine urinalysis is presented. Glucuronide controls for oxazepam, lorazepam and temazepam were treated with IMCSzyme™ recombinant β-glucuronidase. Hydrolysis efficiency was assessed at 55°C and at room temperature (RT) using the recommended optimum pH. Hydrolysis efficiency for four other benzodiazepines was evaluated solely with positive patient samples. Maximum hydrolysis of glucuronide controls at 5 min at RT (mean analyte recovery ≥94% for oxazepam and lorazepam and ≥80% for temazepam) was observed. This was considerably faster than the optimized 30 min incubation time for the abalone β-glucuronidase at 65°C. Mean analyte recovery increased at longer incubation times at 55°C for temazepam only. Total analyte in patient samples compared well to targets from abalone hydrolysis after recombinant β-glucuronidase hydrolysis at RT with no incubation. Some matrix effect, differential reactivity, conjugation variability and transformation impacting total analyte recovery were indicated. The unique potential of the IMCSzyme™ recombinant β-glucuronidase was demonstrated with fast benzodiazepine hydrolysis at RT leading to decreased processing time without the need for heat activation.
    Journal of analytical toxicology 10/2014; 38(8):610-4.
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    ABSTRACT: Driving under the influence (DUI) and DUI drugs (DUID) law enforcement (LE) cases (n = 12,082) where whole blood samples were submitted to ChemaTox Laboratory, Inc. in Boulder, CO, for testing were examined. Of these 12,082 cases, there were 4,235 cannabinoid screens (CS) requested. Samples that yielded a positive CS (n = 2,621) were further analyzed. A total of 1,848 samples were confirmed for Δ9-tetrahydrocannabinol (THC) after a positive CS. Due to a decrease in the confirmation limit of detection (LOD) for THC from 2 to 1 ng/mL, samples that were confirmed for THC and quantitated below 2 ng/mL (n = 250) were considered negative. After this normalization, there were 1,598 samples that were confirmed positive for THC and included in the analysis. The percentage of LE cases with requests for CS for all years was 35%, increasing from 28% in 2011 to 37% in 2013. The positivity rate of CS overall was 62% (range: 59-68% by year) with no significant change over the time frame examined. The percentage of positive CS in which THC was confirmed positive at or above 2 ng/mL (n = 1,598) increased significantly from 28% in 2011 to 65% in 2013. The mean and median THC concentrations were 8.1 and 6.3 ng/mL, respectively (range: 2-192 ng/mL, n = 1,367). The data presented illustrate a statistically significant increase in CS that result in positive THC confirmations. Although the specific cause of this increase is not known at this time, possible ties to ongoing developments in Colorado's marijuana legislation merit further analysis.
    Journal of analytical toxicology 10/2014; 38(8):575-81.
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    ABSTRACT: In December 2012, the possession and private use of limited quantities of marijuana and marijuana products became legal in the state of Washington. At the same time, the state's driving under the influence statutes were amended to include a per se level of 5 ng/mL delta(9)-tetrahydrocannabinol (THC) in whole blood for drivers aged 21 years and older. The aim of this study was to assess the effect of marijuana legalization on the prevalence of marijuana in suspected impaired driving cases. The prevalence of both active THC and its metabolite carboxy-THC detected in such cases pre-legalization was compared with the prevalence post-legalization. In 2009-2012, the average yearly percentage of cases positive for THC and carboxy-THC was 19.1% (range: 18.2-20.2%) and 27.9% (range: 26.3-28.6%), respectively. In 2013, the percentages had significantly increased to 24.9 and 40.0%, respectively (P < 0.05). The median THC concentration over the 5-year period ranged from 5.2 to 6.3 ng/mL, with individual concentrations ranging up to 90 ng/mL. An average of 56% of cases were at or >5 ng/mL over the 5-year period. The prevalence of alcohol and the majority of other drugs in this same population of suspected impaired drivers submitted for testing did not change during this same 5-year period-marijuana was the only drug to show such an increase in frequency. Further, this observed increase remained after the data had been normalized to account for changes in laboratory testing procedures that occurred during this time period. Future studies need be conducted to ascertain whether the observed increase has had any effect on the incidence of crashes, serious injuries and/or traffic fatalities.
    Journal of analytical toxicology 10/2014; 38(8):569-74.
  • Journal of analytical toxicology 10/2014; 38(8):465.
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    ABSTRACT: The Montgomery County Coroner's Office Toxicology Section and the Miami Valley Regional Crime Lab (MVRCL) Drug Chemistry Section have been receiving case work in drug seizures, death cases and human performance cases involving products marketed as heroin or as illicit fentanyl. Upon analysis by the Drug Chemistry Section, these products were found to contain various drug(s) including illicit fentanyl only, illicit fentanyl and heroin, illicit fentanyl and cocaine and illicit fentanyl, heroin and cocaine. Both the Chemistry and Toxicology Sections began seeing these combinations starting in late October 2013. The percentage of the combinations encountered by the MVRCL as well as the physical appearance of the product, and the results of presumptive screening tests will be discussed. The demographics of the users and the results of toxicology and autopsy findings on the decedents will also be discussed. According to regional drug task force undercover agents, there is evidence that some of the products are being sold as illicit fentanyl and not just as a heroin product. Also, there is no evidence to support that the fentanyl source is being diverted from pharmaceutical grade fentanyl. The chemistry section currently has over 109 confirmed cases, and the toxicology section currently has 81 confirmed drug deaths, 8 driving under the influence of drugs and 1 suicidal hanging. Both sections are continuing to see these cases at the present time.
    Journal of analytical toxicology 10/2014; 38(8):592-8.
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    ABSTRACT: This is the first reported case of α-pyrrolidinovalerophenone (α-PVP), methylone and ethylone in a suspected impaired driving case in the state of Washington. An initial traffic stop by law enforcement was made of a driver due to poor navigation of the roadway. The drug recognition expert (DRE) officer observed slurred speech, bloodshot watery eyes, dilated pupils, involuntary muscle movements and an elevated pulse and blood pressure. The DRE deduced that the driver was likely under the influence of central nervous system (CNS) stimulants, specifically 'bath salts'. Routine testing of the blood did not reveal the presence of alcohol or common drugs of abuse. Upon further review of the officer's report and the unconfirmed identification of α-PVP, blood was sent to NMS Labs in Willow Grove, PA, USA for bath salts and stimulant designer drugs testing. Analysis was conducted by liquid chromatography-time-of-flight mass spectrometry with the following results: 63 ng/mL α-PVP, 6.1 ng/mL methylone and positive for ethylone. These results are consistent with the DRE opinion of driving performance being impaired by a CNS stimulant.
    Journal of analytical toxicology 10/2014; 38(8):615-7.
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    ABSTRACT: Methadone is difficult to administer as a therapeutic agent because of a wide range of interindividual pharmacokinetics, likely due to genetic variability of the CYP450 enzymes responsible for metabolism to its principal metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). CYP3A4 is one of the primary CYP450 isoforms responsible for the metabolism of methadone to EDDP in humans. The purpose of this study was to evaluate the role of CYP3A4 genetic polymorphisms in accidental methadone fatalities. A study cohort consisting of 136 methadone-only and 92 combined methadone/benzodiazepine fatalities was selected from cases investigated at the West Virginia and Kentucky Offices of the Chief Medical Examiner. Seven single nucleotide polymorphisms (SNPs) were genotyped within the CYP3A4 gene. Observed allelic and genotypic frequencies were compared with expected frequencies obtained from The National Center for Biotechnology Information dbSNP database. SNPs rs2242480 and rs2740574 demonstrated an apparent enrichment within the methadone-only overdose fatalities compared with the control group and the general population. This enrichment was not apparent in the methadone/benzodiazepine cases for these two SNPs. Our findings indicate that there may be two or more SNPs on the CYP3A4 gene that cause or contribute to the methadone poor metabolizer phenotype.
    Journal of analytical toxicology 10/2014; 38(8):541-7.
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    ABSTRACT: Designer drugs appear to be increasing in popularity because of the ease of obtaining these constituents, the lack of ability to identify the substance(s) in routine drug screening, the appeal of the drug(s) being 'safe' due to them being marketed as a 'legal high' and possibly due to stronger restrictions that are being placed on prescription drugs. As components of designer drugs are identified and regulated by the DEA, new constituents, or analogs, of these designer drugs are being manufactured to circumvent legislation. 2,5-Dimethoxy-4-chloroamphetamine (DOC) is a substituted alpha-methylated phenethylamine and acts as a selective serotonin receptor partial agonist. There is limited literature on this particular compound and no literature that attributes death to use of this drug alone. We present a case of a 37-year-old male found at home lying face down next to a book titled 'Psychedelic Chemistry' by Michael Valentine Smith and in the early stages of decomposition. The decedent was a known methamphetamine abuser. A peripheral blood sample collected at autopsy was sent to toxicology for routine analysis. Results yielded negative for the drugs of abuse classes on the enzyme-linked immunosorbent assay screen but was positive for DOC during routine GC-MS analysis. A urine sample collected at autopsy was subjected to a routine urine liquid/liquid analysis via GC-MS, and the specimen was positive for DOC. Quantification analyses showed DOC concentration levels to be 377 ng/mL in iliac blood; 3,193 ng/mL in urine; 3,143 ng/g in liver and 683 ng/g in brain. DOC was not detected in the gastric contents. Caffeine was the only other compound detected in blood and urine. Due to the lack of literature, we believe that this is the first case where death can be attributed to DOC alone.
    Journal of analytical toxicology 10/2014; 38(8):589-91.
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    ABSTRACT: During prolonged strenuous exercise, racehorses can experience acidemia. To counteract this phenomenon, trainers can administer blood alkalizing agents that raise the plasma pH and total carbon dioxide (TCO2) concentration. In Illinois, the administrative threshold for TCO2 in plasma is 37.0 mmol/L. Because accuracy in the reported measurement of TCO2 must be ensured, uncertainty measurements are often issued alongside the reported concentrations. We report a validated method for measuring TCO2 levels in equine plasma using the Beckman UniCel DxC 600. A six-point calibration curve ranging from 5 to 50 mmol/L is analyzed along with controls at four TCO2 levels with each set of samples. Using this method, we collected data from 5,199 race samples during 2012, with 134 being from thoroughbred horses and 5,065 from standardbred horses. During method validation, uncertainty was determined using the simplified Guide to the Expression of Uncertainty in Measurement approach and was found to be 3% at 99.7% confidence level with eight measurements. Additionally, to investigate other variables that could have an effect on TCO2 levels, we collected the gender, breed, Lasix(®) status, strong ion concentration, pre- or post-race collection time and track location of all horses tested during that year. The samples had an overall mean TCO2 concentration of 30.5 ± 2.0 mmol/L. The other physiological and environmental data were analyzed using analysis of covariance tables. These results indicate gender, breed, furosemide status, collection time and track location to be strongly correlated (P < 0.0001) to TCO2 levels. Thoroughbred status was found to have no effect. Finally, TCO2 concentrations were highly correlated (P < 0.0001) to sodium and chloride ion concentrations. No correlation was found between TCO2 and potassium concentrations. The results show that there are several environmental and physiological factors that can affect TCO2 concentrations. The concentration of other strong ions present in the blood may indicate doping status.
    Journal of analytical toxicology 10/2014; 38(8):536-40.