Drug Testing and Analysis

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Tần suất xuất hiện của các chất hướng thần mới trong mẫu sinh học – Tổng quan ba năm về các vụ án ở Ba Lan
Drug Testing and Analysis - Tập 8 Số 1 - Trang 63-70 - 2016
Piotr Adamowicz, Joanna Gieroń, Dominika Gil, Wojciech Lechowicz, Agnieszka Skulska, Bogdan Tokarczyk
Các chất hướng thần mới (NPS) là thách thức cho các nhà độc chất pháp y và lâm sàng, cũng như các nhà lập pháp. Chúng tôi trình bày phát hiện của mình từ các trường hợp mà các NPS đã được phát hiện trong vật liệu sinh học. Trong khoảng thời gian ba năm từ 2012–2014, chúng tôi đã phát hiện NPS trong 112 trường hợp (trong tổng số 1058 đã phân tích), với 75 trường hợp chỉ riêng năm 2014. Mức độ phổ biến của tất cả các NPS (15,1–17,6%) tương tự như amphetamine chỉ phát hiện được trong 15,1–16,5% trường hợp. Các loại thuốc mới được phát hiện thuộc các lớp sau: cathinones (88%), cannabinoid tổng hợp (5%), phenethylamines (3%), piperazines và piperidines (3%), arylalkylamines (1%) và khác (1%). Các loại thuốc được phát hiện (theo thứ tự giảm dần tần suất): 3‐MMC (50), α‐pyrrolidinopentiophenone (α‐PVP) (23), pentedrone (16), 3',4'‐methylenedioxy‐α‐pyrrolidinobutyrophenone (MDPBP) (12), cannabinoid tổng hợp UR‐144 (7), ethcathinone (5), mephedrone (5), methylenedioxypyrovalerone (MDPV) (4), 4‐methylethcathinone (4‐MEC) (3), buphedrone (3), desoxypipradrol (2‐DPMP) (3), methylone (2) và 2C‐B (2). Trong các trường hợp đơn lẻ, phát hiện 2‐methylmethcathinone (2‐MMC), 2C‐P, eutylone, 25I‐NBOMe, meta‐chlorophenylpiperazine (mCPP), ephedrone, methiopropamine (MPA) và 5‐(2‐aminopropyl)benzofuran (5‐APB). Một NPS là tác nhân duy nhất trong 35% tổng số trường hợp và hai hoặc nhiều NPS có mặt trong 19% các trường hợp. NPS (một hoặc nhiều chất) cùng với các thuốc truyền thống khác (như amphetamine, cannabinoid, cocaine và benzodiazepines) đã được phát hiện trong hầu hết (65%) các trường hợp. NPS thường xuyên được phát hiện trong máu của tài xế lái xe là thách thức cho các nhà độc chất do thiếu dữ liệu về ảnh hưởng của chúng đến hiệu suất tâm lý vận động. Một đánh giá về nồng độ đã cho thấy một dãy giá trị rộng trong các loại trường hợp khác nhau, đặc biệt là lái xe dưới ảnh hưởng của ma túy (DUID) và ngộ độc. Bản quyền © 2015 John Wiley & Sons, Ltd.
#chất hướng thần mới #độc chất pháp y #phân tích sinh học #tài xế dưới ảnh hưởng #NPS #cathinones #cannabinoid tổng hợp #phenethylamines #piperazines #piperidines #arylalkylamines #ảnh hưởng tâm lý vận động #Ba Lan
Prevalence of new psychoactive substances and prescription drugs in the Belgian driving under the influence of drugs population
Drug Testing and Analysis - Tập 10 Số 3 - Trang 539-547 - 2018
Sarah M. R. Wille, Camille Richeval, Florian Hakim, Jean‐Michel Gaulier, Vincent Di Fazio, Luc Humbert, Nele Samyn, Delphine Allorge
Driving under the influence of drugs (DUID) is a worldwide problem. Several countries have adopted DUID legislations which prove their deterrent effect and impact on road safety. However, the use of new psychoactive substances (NPS) and prescription drugs is not known, as the applied roadside screening tests have not yet been adapted for these compounds. In this study, 558 blood samples obtained during roadside controls in Belgium (January to August 2015) after a positive Drugwipe 5S® test and 199 oral fluid (OF) samples obtained from negatively screened test pads were analyzed. The NPS positivity rate was 7% in blood, while it reached 11% in OF. NPS detected were: diphenidine, ketamine, 4‐fluoroamphetamine, 2‐amino‐indane, methoxetamine, α‐PVP, methiopropamine, a mix of 5‐MAPB/5‐EAPB, TH‐PVP, mephedrone, methedrone, 4‐methylethylcathinone, 5‐MeO‐DALT, 4‐Acetoxy‐DiPT, AB Fubinaca, FUB‐JWH018, JWH020, trifluoromethylphenylpiperazine, and ethylphenidate. Moreover, 17% of blood samples (and 5% of OF) contained an analgesic drug, 10% (0.5%) a benzodiazepine/hypnotic, 5% (2%) an antidepressant, 2% (3%) an antipsychotic, 2% an antiepileptic drug, and 1% methylphenidate. The presence of NPS in the young (and predominately male) DUID population is proven. Furthermore, a high level of poly‐drug use including combinations of NPS, licit, and drugs of abuse was observed. Further research concerning the development of on‐site NPS detection techniques should be established. Meanwhile, the effects of combined drug use on driving ability and the physical/psychological signs after NPS use should be performed to improve the on‐site DUID detection of NPS by police officers, so they can engage in blood sampling for a general unknown screening.
Analysis of NRG ‘legal highs’ in the UK: identification and formation of novel cathinones
Drug Testing and Analysis - Tập 3 Số 9 - Trang 569-575 - 2011
Simon D. Brandt, Sally Freeman, Harry Sumnall, Fiona Measham, Jon C. Cole
A large number of cathinone derivatives have shown a wide range of bioactive properties, attracting great interest from communities associated with pharmaceutical research. Some of these derivatives have gained popularity as so‐called recreational ‘legal highs’ due to their availability on the Internet and high street shops. A previous study described the qualitative analysis of 24 ‘legal high’ Energy‐1 (NRG‐1) and NRG‐2 products obtained from 18 websites following the ban on mephedrone and derivatives in April 2010. The majority of these products contained a mixture of cathinones just carrying a new label. Here, three additional cathinone products have been detected; two from an NRG‐1 sample and one from an NRG‐3 sample. This report describes their identification. NRG‐1 sample 1 consisted of a mixture of 4 cathinones namely 4‐fluoromethcathinone (1), 1‐(3,4‐methylenedioxyphenyl)‐2‐(methylamino)pentan‐1‐one (pentylone, 2), 3,4‐methylenedioxy‐α‐pyrrolidinobutyrophenone (MDPBP, 3) and 3,4‐methylenedioxypyrovalerone (MDPV, 4). The sample labelled as NRG‐3 (mislabelled with the chemical structure of mephedrone) consisted of a mixture of 4‐methyl‐α‐pyrrolidinopropiophenone (MPPP, 5) and (2), whereas the remaining NRG‐1 sample 2 (also mislabelled with the chemical structure of mephedrone) consisted of a mixture of (2) and (3). Qualitative analyses were carried out by GC‐(EI/CI)‐MS, NMR spectroscopy and confirmation by preparation of standards. The preparation of brominated precursors carrying the 3,4‐methylenedioxyphenyl nucleus revealed extensive α,α‐dibromination: the mass spectral and NMR data of these intermediates are also presented and discussed. Copyright © 2010 John Wiley & Sons, Ltd.
‘Smoking’ mephedrone: The identification of the pyrolysis products of 4‐methylmethcathinone hydrochloride
Drug Testing and Analysis - Tập 5 Số 5 - Trang 291-305 - 2013
Pierce V. Kavanagh, John E. O’Brien, John D. Power, Brian Talbot, Seán D. McDermott
The ring‐substituted cathinone – mephedrone – has gained popularity among recreational drug users over the past several years. It is generally consumed orally or by snorting but reports indicate that it is also ingested by vaporization/inhalation. This study examines the pyrolysis products produced by heating mephedrone under using simulated ‘meth pipe’ conditions. Thirteen pyrolysis products were identified, the major ones being iso‐mephedrone, 4‐methylpropiophenone, 4‐methylphenylacetone, two pyrazine derivatives formed by dimerization of mephedrone, N‐methylated mephedrone (N,N,4‐trimethylcatinone), two hydroxylated oxidation products and a diketone. Other minor products formed were identified as 4‐methylacetophenone, two α‐chloro ketones and N‐methylated iso‐mephedrone. Copyright © 2012 John Wiley & Sons, Ltd.
Lefetamine‐derived designer drugs <i>N</i>‐ethyl‐1,2‐diphenylethylamine (NEDPA) and <i>N‐iso</i>‐propyl‐1,2‐diphenylethylamine (NPDPA): Metabolism and detectability in rat urine using GC‐MS, LC‐MS<sup>n</sup> and LC‐HR‐MS/MS
Drug Testing and Analysis - Tập 6 Số 10 - Trang 1038-1048 - 2014
Carina S. D. Wink, Golo M. J. Meyer, Dirk K. Wissenbach, Andrea Jacobsen‐Bauer, Markus R. Meyer, Hans H. Maurer
N‐Ethyl‐1,2‐diphenylethylamine (NEDPA) and N‐iso‐propyl‐1,2‐diphenylethylamine (NPDPA) are two designer drugs, which were confiscated in Germany in 2008. Lefetamine (N,N‐dimethyl‐1,2‐diphenylethylamine, also named L‐SPA), the pharmaceutical lead of these designer drugs, is a controlled substance in many countries. The aim of the present work was to study the phase I and phase II metabolism of these drugs in rats and to check for their detectability in urine using the authors’ standard urine screening approaches (SUSA). For the elucidation of the metabolism, rat urine samples were worked up with and without enzymatic cleavage, separated and analyzed by gas chromatography‐mass spectrometry (GC‐MS) and liquid chromatography‐high resolution‐tandem mass spectrometry (LC‐HR‐MS/MS). According to the identified metabolites, the following metabolic pathways for NEDPA and NPDPA could be proposed: N‐dealkylation, mono‐ and bis‐hydroxylation of the benzyl ring followed by methylation of one of the two hydroxy groups, combinations of these steps, hydroxylation of the phenyl ring after N‐dealkylation, glucuronidation and sulfation of all hydroxylated metabolites. Application of a 0.3 mg/kg BW dose of NEDPA or NPDPA, corresponding to a common lefetamine single dose, could be monitored in rat urine using the authors’ GC‐MS and LC‐MSn SUSA. However, only the metabolites could be detected, namely N‐deethyl‐NEDPA, N‐deethyl‐hydroxy‐NEDPA, hydroxy‐NEDPA, and hydroxy‐methoxy‐NEDPA or N‐de‐iso‐propyl‐NPDPA, N‐de‐iso‐propyl‐hydroxy‐NPDPA, and hydroxy‐NPDPA. Assuming similar kinetics, an intake of these drugs should also be detectable in human urine. Copyright © 2014 John Wiley & Sons, Ltd.
Sewage‐based epidemiology in monitoring the use of new psychoactive substances: Validation and application of an analytical method using LC‐MS/MS
Drug Testing and Analysis - Tập 7 Số 9 - Trang 812-818 - 2015
Juliet Kinyua, Adrian Covaci, Walid Maho, Ann‐Kathrin McCall, Hugo Neels, Alexander L.N. van Nuijs
Sewage‐based epidemiology (SBE) employs the analysis of sewage to detect and quantify drug use within a community. While SBE has been applied repeatedly for the estimation of classical illicit drugs, only few studies investigated new psychoactive substances (NPS). These compounds mimic effects of illicit drugs by introducing slight modifications to chemical structures of controlled illicit drugs. We describe the optimization, validation, and application of an analytical method using liquid chromatography coupled to positive electrospray tandem mass spectrometry (LC‐ESI‐MS/MS) for the determination of seven NPS in sewage: methoxetamine (MXE), butylone, ethylone, methylone, methiopropamine (MPA), 4‐methoxymethamphetamine (PMMA), and 4‐methoxyamphetamine (PMA). Sample preparation was performed using solid‐phase extraction (SPE) with Oasis MCX cartridges. The LC separation was done with a HILIC (150 x 3 mm, 5 µm) column which ensured good resolution of the analytes with a total run time of 19 min. The lower limit of quantification (LLOQ) was between 0.5 and 5 ng/L for all compounds. The method was validated by evaluating the following parameters: sensitivity, selectivity, linearity, accuracy, precision, recoveries and matrix effects. The method was applied on sewage samples collected from sewage treatment plants in Belgium and Switzerland in which all investigated compounds were detected, except MPA and PMA. Furthermore, a consistent presence of MXE has been observed in most of the sewage samples at levels higher than LLOQ. Copyright © 2015 John Wiley & Sons, Ltd.
<i>In vitro</i> and <i>in vivo</i> human metabolism of the synthetic cannabinoid AB‐CHMINACA
Drug Testing and Analysis - Tập 7 Số 10 - Trang 866-876 - 2015
Claudio Erratico, Noelia Negreira, Helia Norouzizadeh, Adrian Covaci, Hugo Neels, Kristof E. Maudens, Alexander L.N. van Nuijs
N‐[(1S)‐1‐(aminocarbonyl)‐2‐methylpropyl]‐1‐(cyclohexylmethyl)‐1H‐indazole‐3‐carboxamide (AB‐CHMINACA) is a recently introduced synthetic cannabinoid. At present, no information is available about in vitro or in vivo human metabolism of AB‐CHMINACA. Therefore, biomonitoring studies to screen AB‐CHMINACA consumption lack any information about the potential biomarkers (e.g. metabolites) to target. To bridge this gap, we investigated the in vitro metabolism of AB‐CHMINACA using human liver microsomes (HLMs). Formation of AB‐CHMINACA metabolites was monitored using liquid chromatography coupled to time‐of‐flight mass spectrometry. Twenty‐six metabolites of AB‐CHMINACA were detected including seven mono‐hydroxylated and six di‐hydroxylated metabolites and a metabolite resulting from N‐dealkylation of AB‐CHMINACA, all produced by cytochrome P450 (CYP) enzymes. Two carboxylated metabolites, likely produced by amidase enzymes, and five glucuronidated metabolites were also formed. Five mono‐hydroxylated and one carboxylated metabolite were likely the major metabolites detected. The involvement of individual CYPs in the formation of AB‐CHMINACA metabolites was tested using a panel of seven human recombinant CYPs (rCYPs). All the hydroxylated AB‐CHMINACA metabolites produced by HLMs were also produced by the rCYPs tested, among which rCYP3A4 was the most active enzyme. Most of the in vitro metabolites of AB‐CHMINACA were also present in urine obtained from an AB‐CHMINACA user, therefore showing the reliability of the results obtained using the in vitro metabolism experiments conducted to predict AB‐CHMINACA in vivo metabolism. The AB‐CHMINACA metabolites to target in biomonitoring studies using urine samples are now reliably identified and can be used for routine analysis. Copyright © 2015 John Wiley & Sons, Ltd.
Analytical characterization of three cathinone derivatives, 4‐MPD, 4F–PHP and bk‐EPDP, purchased as bulk powder from online vendors
Drug Testing and Analysis - Tập 10 Số 2 - Trang 372-378 - 2018
Orapan Apirakkan, Anca Frinculescu, Trevor Shine, Mark C. Parkin, Agostino Cilibrizzi, Nunzianda Frascione, Vincenzo Abbate
Novel emerging drugs of abuse, also referred as new psychoactive substances, constitute an ever‐changing mixture of chemical compounds designed to circumvent legislative controls by means of chemical modifications of previously banned recreational drugs. One such class, synthetic cathinones, namely β‐keto derivatives of amphetamines, has been largely abused over the past decade. A number of new synthetic cathinones are detected each year, either in bulk powders/crystals or in biological matrices. It is therefore important to continuously monitor the supply of new synthetic derivatives and promptly report them. By using complementary analytical techniques (i.e. one‐ and two‐dimensional NMR, FT‐IR, GC–MS, HRMS and HPLC‐UV), this study investigates the detection, identification and full characterization of 1‐(4‐methylphenyl)‐2‐(methylamino)pentanone (4‐methylpentedrone, 4‐MPD), 1‐(4‐fluorophenyl)‐2‐(pyrrolidin‐1‐yl)hexanone (4F–PHP) and 1‐(1,3‐benzodioxol‐5‐yl)‐2‐(ethylamino)‐1‐pentanone (bk‐EPDP), three emerging cathinone derivatives.
The adverse health effects of chronic cannabis use
Drug Testing and Analysis - Tập 6 Số 1-2 - Trang 39-45 - 2014
Wayne Hall, Louisa Degenhardt
This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance – those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment. Copyright © 2013 John Wiley & Sons, Ltd.
Metabolic profiling of isomeric aglycones central‐icaritin (<i>c</i>‐IT) and icaritin (IT) in osteoporotic rats by UPLC‐QTOF‐MS
Drug Testing and Analysis - Tập 7 Số 4 - Trang 309-319 - 2015
Jun Jiang, Liang Feng, Encheng Sun, Haotian Li, Li Cui, Xiaobin Jia
The isomers, although of similarly chemical structures, have different pharmacological activities due to their metabolic processes in vivo. Central‐icaritin (c‐IT) and icaritin (IT) are isomers and major bioactive aglycones of the Herba Epimedii. In this study, we found that the anti‐osteoporotic effect of c‐IT was stronger than IT on bone structural changes in osteoporotic rats evaluated by Micro‐μCT with the parameters of bone mineral density (BMD), bone mineral content (BMC), tissue mineral content (TMC), and tissue mineral density (TMD). c‐IT treatment significantly increased the bone microarchitecture, compared with IT (p < 0.05). In order to explain their differences in anti‐osteoporosis, the metabolic profiling and pathways of c‐IT and IT in the plasma, bile, urine, and faeces of ovariectomized (OVX) rats were investigated by ultra‐performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC‐QTOF‐MS) after oral administration of c‐IT or IT (80 mg/kg). Finally, 59 metabolites of c‐IT and 43 metabolites of IT were identified by elucidating their corresponding quasimolecular ions and fragment ions. IT could be quickly absorbed into blood and reached a maximum plasma concentration, and then be rapidly conversed to its glucuronidation metabolites, most of which were excreted out by urine. Interestingly, the absorbed and conjugated speeds of c‐IT were slower than IT. The metabolic processes of c‐IT existed enterohepatic circulation, which decreased the metabolism and excretion rate of c‐IT, and prolonged the anti‐osteoporosis effect. Our findings provided evidence on the difference on metabolic profiles of c‐IT and IT in osteoporotic rats, which might shed new lights on improving anti‐osteoporotic effects of IT and c‐IT. Copyright © 2014 John Wiley & Sons, Ltd.
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