Simultaneous detection of 93 conventional and emerging drugs of abuse and their metabolites in urine by UHPLC-MS/MS
Introduction
The last decade has seen a rapid and continual growth of novel psychoactive substances (NPS). In 2008, 13 NPS were reported for the first time to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA); by 2012, 73 new drugs were reported within a year [1]. NPS are often sold in disguise as bath salts, plant food, chemical standards, spice mix, herbal incense etc., whilst being explicitly labelled as “Not for human consumption”. They are readily available in head shops, from street dealers and over the Internet [2], [3], [4]. Akin to conventional drugs of abuse, NPS may carry substantial toxicity and even resulting in death. PMMA, mephedrone and other bath salts are notorious examples of highly dangerous NPS that have resulted in numerous fatalities worldwide [2], [3], [5], [6], [7], [8], [9], [10].
Effective clinical and social management of NPS relies on the timely and accurate detection of these substances. Although most NPS bear chemical resemblance to conventional drugs of abuse, their analytical detection remains a great challenge to the laboratory at present. Designer amphetamines such as mephedrone and MDPV, as well as the newly emerging NBOMe compounds, have been reported to be poorly detected by existing immunoassay methods [11], [12]. At present, the comprehensive and simultaneous testing for conventional and novel drugs of abuse appears not to be widely available in most clinical laboratories. The limited availability of testing service and the lack of standardized methodology for their analysis have contributed to the often delayed discovery of NPS in the community.
The early identification of NPS depends on the timely development of methods that are able to detect them with sufficient sensitivity and specificity. Ideally, the analysis of NPS should be incorporated into the routine drugs of abuse screening for regular monitoring of these new drugs with minimal additional effort and cost. Numerous analytical methods have been published for the detection of conventional drugs of abuse [13], [14], [15], [16], [17], [18], [19], [20], [21], NPS [22], [23], [24], [25], [26], [27], [28], [29], or panel(s) of drugs with specific pharmacological/toxicological effects [30], [31], [32], [33], [34], [35], [36], [37], [38], [39] in biological specimens. In contrast, methodologies for the broad-spectrum, simultaneous detection of both conventional as well as emerging drugs of abuse have not been as widely published. Previous reports have utilized a general screening approach [40], [41]. The current study aims to develop a chromatography-mass spectrometry based method for the simultaneous and targeted analysis of over 90 conventional as well as emerging drugs of abuse and their metabolites in urine. The method was validated according to international guidelines and subsequently used to analyse 964 urine samples collected from known drug abusers and high-risk individuals.
Section snippets
Reagents
Reference standards were purchased from Cayman Chemical Company (USA), Lipomed AG (Switzerland), Cerilliant (USA), Toronto Research Chemicals (Canada), National Measurement Institute (Australia), USP (U.S. Pharmacopeial Convention, USA), LGC (UK), Wako (Japan), ChromaDex (USA), Sigma–Aldrich (USA) and International Laboratory USA. Methanol (LCMS grade) was obtained from J.T. Baker (Netherlands), ethyl acetate from Fischer Scientific (UK) and acetonitrile (HPLC grade) from RCI-Labscan
Method development
An LC-MS/MS based method has been established for the simultaneous detection of a broad spectrum of conventional and emerging drugs of abuse and their metabolites in urine (93 analytes in total). Previously published methods on the urinalysis of NPS have predominantly been limited to novel drugs only [26], [27], [47] or panel(s) of specific drug class [32], [33], [34], [35], [36], [39]. The target analytes are drugs that are known to be commonly abused in the local population, as well as their
Conclusion
An LC-MS/MS method has been established that allows the simultaneous detection of over 90 conventional as well as novel psychoactive substances and metabolites in urine samples. The method was successfully applied to authentic specimens for identification of conventional as well as novel drugs of abuse in local drug abusers.
Acknowledgements
This study was supported by the Beat Drugs Fund (Narcotics Division, Security Bureau of the government of Hong Kong SAR), project reference BDF101021. The authors are also grateful for the generous assistance from Dr Man-Li Tse, Ms Carol Ng and participating clinical divisions within the Hospital Authority and social service units (including Evergreen Lutheran Centre, Rainbow Lutheran Centre, Cheer Lutheran Centre, the Society of Rehabilitation and Crime Prevention, Operation Dawn, Caritas Wong
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