The analysis and detection of new psychoactive substances in biological matrices

RA1001 Forensic Medicine. Medical jurisprudence. Legal medicine

Nisbet, Lorna A. ; Wylie, Fiona

University:University of Glasgow

Department:School of Medicine, Dentistry & Nursing

关键词: NPS, New psychoactive substances, NBOMes, Cathinones, Forensic Toxicology, GC-MS.;   

Others  :  http://theses.gla.ac.uk/7213/7/2015NisbetPhD.pdf

来源: University of Glasgow

【 摘 要 】

New psychoactive substances (NPSs) have appeared on the recreational drugmarket at an unprecedented rate in recent years. Many are not new drugs butfailed products of the pharmaceutical industry. The speed and variety of drugsentering the market poses a new complex challenge for the forensic toxicologycommunity. The detection of these substances in biological matrices can bedifficult as the exact compounds of interest may not be known. Many NPS aresold under the same brand name and therefore users themselves may not knowwhat substances they have ingested.The majority of analytical methods for the detection of NPSs tend to focus on aspecific class of compounds rather than a wide variety. In response to this, arobust and sensitive method was developed for the analysis of various NPS bysolid phase extraction (SPE) with gas chromatography mass spectrometry (GCMS).Sample preparation and derivatisation were optimised testing a range ofSPE cartridges and derivatising agents, as well as derivatisation incubation timeand temperature. The final gas chromatography mass spectrometry method wasvalidated in accordance with SWGTOX 2013 guidelines over a wide concentrationrange for both blood and urine for 23 and 25 analytes respectively. This includedthe validation of 8 NBOMe compounds in blood and 10 NBOMe compounds inurine. This GC-MS method was then applied to 8 authentic samples withconcentrations compared to those originally identified by NMS laboratories.The rapid influx of NPSs has resulted in the re-analysis of samples and thus, thestability of these substances is crucial information. The stability of mephedronewas investigated, examining the effect that storage temperatures andpreservatives had on analyte stability daily for 1 week and then weekly for 10weeks.Several laboratories identified NPSs use through the cross-reactivity of thesesubstances with existing screening protocols such as ELISA. The application ofImmunalysis ketamine, methamphetamine and amphetamine ELISA kits for thedetection of NPS was evaluated. The aim of this work was to determine if anycross-reactivity from NPS substances was observed, and to determine whetherthese existing kits would identify NPS use within biological samples. The cross-reactivity of methoxetamine, 3-MeO-PCE and 3-MeO-PCP for differentcommercially point of care test (POCT) was also assessed for urine.One of the newest groups of compounds to appear on the NPS market is theNBOMe series. These drugs pose a serious threat to public health due to theirhigh potency, with fatalities already reported in the literature. Thesecompounds are falsely marketed as LSD which increases the chance of adverseeffects due to the potency differences between these 2 substances. A liquidchromatography tandem mass spectrometry (LC-MS/MS) method was validated inaccordance with SWGTOX 2013 guidelines for the detection for 25B, 25C and 25I-NBOMe in urine and hair.Long-Evans rats were administered 25B-, 25C- and 25I-NBOMe at doses rangingfrom 30-300 µg/kg over a period of 10 days. Tail flick tests were then carried outon the rats in order to determine whether any analgesic effects were observedas a result of dosing. Rats were also shaved prior to their first dose and reshavedafter the 10-day period. Hair was separated by colour (black and white)and analysed using the validated LC-MS/MS method, assessing the impact haircolour has on the incorporation of these drugs. Urine was collected from therats, analysed using the validated LC-MS/MS method and screened for potentialmetabolites using both LC-MS/MS and quadrupole time of flight (QToF)instrumentation.