The current immunoassay screening methodologies used to detect sympathomimetic amines within the context of workplace drug testing may fail to detect a number of the emerging designer drugs, for example β-keto amphetamines and piperazine derivatives, commonly referred to as 'legal highs'. Therefore, a rapid multi-analyte qualitative screening method, using ultra-high-pressure liquid chromatography-tandem mass spectrometry (LC-MS/MS), was investigated for analysis of new designer drugs that have emerged from the former legal highs market. Eight analytes were targeted as model compounds: 4-methylmethcathinone (mephedrone), 3,4-methylenedioxymethcathinone (bk-MDMA, 'methylone'), 2-methylamino-1-(3,4-methylenedioxyphenyl)butan-1-one (bk-MBDB, 'butylone'), 4-methoxymethcathinone (bk-PMMA, 'methedrone'), 1-benzylpiperazine (BZP), 1-(3-trifluoromethyl phenyl)-piperazine (TFMPP), 1-(3-chloro phenyl)-piperazine (mCPP), and 3, 4-methylenedioxypyrovalerone (MDPV). The LC-MS/MS method developed encompassed direct analysis following a 1:4 dilution of urine with mobile phase to reduce matrix effects. Although not all compounds were completely resolved chromatographically, two product ions conferred sufficient specificity to allow target analyte identification. Although all target analytes were readily detected at 500 ng/ml, a cut-off of 1000 ng/ml was chosen to mirror the amphetamine screening cut-off commonly used for routine analysis of workplace drug testing samples. In conclusion, direct analysis using LC-MS/MS offers an attractive way forward for the development of a rapid routine screen for new psychoactive substances, particularly given the growing number of novel compounds.
A major toxicological challenge is distinguishing whether morphine in urine, in the absence of 6-monoacetylmorphine (6-MAM), originates from 'street' heroin use or poppy seed ingestion. Manufacturing byproducts from the synthesis of illicit heroin include those that originate from the reaction of acetic anhydride with the alkaloid impurity, thebaine, which undergoes skeletal rearrangement, resulting in compounds with a 2-(N-methylacetamido)ethyl side-chain. The hypothesis that the tertiary amide in this side-chain is resistant to endogenous hydrolysis was supported from in-vitro experiments; a glucuronide metabolite (designated 'ATM4G') was identified that may be used as a marker of 'street' heroin administration. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for this metabolite was then performed on selected urine specimens from 22 known heroin users, these being negative on routine testing for 6-MAM by gas chromatography-mass spectrometry (GC-MS), using the generally applied reporting threshold of 10 ng/mL, but positive for the presence of morphine. Peaks corresponding to the retention time for the metabolite marker were clearly observed for 16 of the 22 samples, with variations of the ratios of its three dependent ions being within ± 30% of that produced in vitro. Conversely, 6-MAM was detected in only 3 samples, but at concentrations <1 ng/mL. Such a high frequency for the presence of the metabolite marker in urine, in the absence of 6-MAM, is noteworthy and suggests that detection of this metabolite may offer an important advance in forensic toxicology, allowing the development of a new and more definitive test for heroin abuse and thus a potential solution to the so-called 'poppy seed defense'.
Mephedrone and one of its metabolites have been detected for the first-time in fingerprints collected from a controlled human mephedrone administration study.
Mephedrone is a new psychoactive substance known to be unstable in biological matrices stored at room temperature or refrigerated. While the instability of mephedrone has been investigated before, there is currently no data regarding the stability of mephedrone metabolites. In this study, a liquid chromatography–tandem mass spectrometry method for the simultaneous quantification of mephedrone and five of its phase I metabolites (dihydro‐mephedrone, nor‐mephedrone, hydroxytolyl‐mephedrone, 4‐carboxy‐mephedrone and dihydro‐nor‐mephedrone) in human whole blood has been developed and validated. Samples were extracted by a mixed mode solid‐phase extraction and analyzed on a pentafluorophenylpropyl column. The method was successfully validated for selectivity, linearity (0.2–2 to 10–100 ng/mL), limits of detection (50–500 pg/mL) and quantification (200–2000 pg/mL), precision (0.924–8.27%), accuracy (86.6–115%), carryover, recovery (32.5–88.3%), and matrix effects (71.0–108%). Analyte stability in human whole blood preserved with sodium fluoride/potassium oxalate was assessed at +4°C and −20°C after 24 hours, 48 hours, 4 days, and 10 days of storage. Instability was observed in samples stored at +4°C: nor‐mephedrone and 4‐carboxy‐mephedrone lost 40.2 ± 6.7% and 48.1 ± 4.8%, respectively, of their initial concentration at low concentration level and 33.8 ± 4.2% and 44.6 ± 6.5%, respectively, at high concentration level after 10 days. All analytes were more stable at −20°C where the highest loss of 22.6 ± 6.9% was observed for 4‐carboxy‐mephedrone after 10 days. This is the first time stability of mephedrone metabolites in human whole blood has been assessed, indicating −20°C to be the recommended storage condition for all analytes in clinical settings.
These European Guidelines for Workplace Drug Testing in Urine have been prepared and updated by the European Workplace Drug Testing Society (EWDTS). The first version of these urine guidelines was published in 2002. Since then, the guidelines have been followed by many laboratories in different European countries and their role has been essential particularly in countries lacking legislation for workplace drug testing. In 2014, the EWDTS started a guidelines updating project and published a new version of the urine guidelines in 2015. Here we represent this updated version of the urine guidelines. The European Guidelines are designed to establish best practice procedures whilst allowing individual countries to operate within the requirements of national customs and legislation. The EWDTS recommends that all European laboratories that undertake legally defensible workplace drug testing should use these guidelines as a template for accreditation. Copyright © 2017 John Wiley & Sons, Ltd.
Mephedrone is a popular synthetic cathinone, known for its psychostimulant effects. At present, there is no data available on the pharmacokinetics of mephedrone and its metabolites in concurrently collected whole blood and plasma samples after a controlled intranasal administration to healthy volunteers. In this study, six healthy male volunteers nasally insufflated 100 mg of pure mephedrone hydrochloride (Day 1). Whole blood and plasma samples were collected at different timepoints after the administration and were analysed for the presence of mephedrone and its metabolites, dihydro-mephedrone (DHM), nor-mephedrone (NOR), hydroxytolyl-mephedrone (HYDROXY), 4-carboxy-mephedrone (4-CARBOXY) and dihydro-nor-mephedrone (DHNM), by validated liquid chromatography–tandem mass spectrometry methods. All analytes were detected in whole blood and plasma for 6 h post administration, with mephedrone and NOR also being detectable on Day 2 in some participants. 4-CARBOXY, followed by NOR, were the most abundant metabolites in both matrices. Compared to other psychostimulants, mephedrone showed rapid absorption (mean Tmax of 52.5 ± 20.7 min in plasma and 55.0 ± 18.2 min in whole blood) and elimination (mean t1/2 of 1.98 ± 0.30 h in plasma and 2.12 ± 0.33 h in whole blood). In addition, statistical analysis showed that median whole blood to plasma distribution ratios, reported here for the first time, were statistically different from 1 (unity) for mephedrone (median: 1.11), DHM (median: 1.30) and NOR (median: 0.765). It is hoped that the study will aid forensic and clinical toxicologists in detection, identification and interpretation of cases associated with mephedrone use.
Over the past decade, oral fluid has established itself as a robust testing matrix for monitoring drug use or misuse. Commercially available collection devices provide opportunities to collect and test oral fluid by the roadside and near-patient testing with both clinical and criminal justice applications. One of the main advantages of oral fluid relates to the collection of the matrix which is non-invasive, simple, and can be carried out under direct observation making it ideal for workplace drug testing. Laboratories offering legally defensible oral fluid workplace drug testing must adhere to national and international quality standards (ISO/IEC 17025); however, these standards do not address issues specific to oral fluid testing. The European Workplace Drug Testing Society (EWDTS) recognizes the importance of providing best practice guidelines to organizations offering testing and those choosing to use oral fluid drug testing to test their employees. The aim of this paper is to present the EWDTS guidelines for oral fluid workplace drug testing.
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