Drug Testing and Analysis
1942-7611
1942-7603
Anh Quốc
Cơ quản chủ quản: John Wiley and Sons Ltd , WILEY
Lĩnh vực:
Analytical ChemistryPharmaceutical ScienceSpectroscopyEnvironmental Chemistry
Các bài báo tiêu biểu
The adverse health effects of chronic cannabis use 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.
Tập 6 Số 1-2 - Trang 39-45 - 2014
Analysis of NRG ‘legal highs’ in the UK: identification and formation of novel cathinones 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.
Tập 3 Số 9 - Trang 569-575 - 2011
Detection of urinary metabolites of AM‐2201 and UR‐144, two novel synthetic cannabinoids Synthetic cannabinoids are the psychotropic compounds frequently identified as active components of smoking mixtures easily available via the Internet in several countries. These herbal blends have become extremely popular as a legal alternative to cannabis‐based products and are difficult to detect by regular drug tests. Here we report on an in vitro and in vivo metabolism of AM‐2201, 1‐[(5‐fluoropentyl)‐1H ‐indol‐3‐yl]‐(naphthalen‐1‐yl)methanone, and UR‐144 (KM‐X1), (1‐pentylindol‐3‐yl)‐(2,2,3,3‐tetramethylcyclopropyl)methanone isolated using preparative liquid chromatography from the smoking mixtures sold in Russia. After incubation with human liver microsomes (HLM) as well as with cytochrome isoenzymes 3A4 and 2B6, the metabolic pathways were identified by means of liquid chromatography – triple quadrupole and high resolution mass spectrometry with electrospray ionization in positive mode. It was found that the in vitro reactions include mono‐ and dihydroxylation, loss of N ‐alkyl side chain and formation of dihydrodiol metabolites in case of AM‐2201. The HLM were found to be superior over the other two isoenzymes for generation of cannabinoid metabolites. Finally, forensic urine samples were analyzed to validate the in vitro data and it has been shown that for both cannabimimetics the recommended screening targets are the monohydroxylated metabolites. Copyright © 2012 John Wiley & Sons, Ltd.
Tập 4 Số 10 - Trang 745-753 - 2012
Screening for the synthetic cannabinoid JWH‐018 and its major metabolites in human doping controls Referred to as ‘spice’, several new drugs, advertised as herbal blends, have appeared on the market in the last few years, in which the synthetic cannabinoids JWH‐018 and a C8 homologue of CP 47,497 were identified as major active ingredients. Due to their reported cannabis‐like effects, many European countries have banned these substances. The World Anti‐Doping Agency has also explicitly prohibited synthetic cannabinoids in elite sport in‐competition. Since urine specimens have been the preferred doping control samples, the elucidation of the metabolic pathways of these substances is of particular importance to implement them in sports drug testing programmes. In a recent report, an in vitro phase‐I metabolism study of JWH‐018 was presented yielding mainly hydroxylated and N ‐dealkylated metabolites. Due to these findings, a urine sample of a healthy man declaring to have smoked a ‘spice’ product was screened for potential phase‐I and ‐II metabolites by high‐resolution/high‐accuracy mass spectrometry in the present report. The majority of the phase‐I metabolites observed in earlier in vitro studies of JWH‐018 were detected in this urine specimen and furthermore most of their respective monoglucuronides. As no intact JWH‐018 was detectable, the monohydroxylated metabolite being the most abundant one was chosen as a target analyte for sports drug testing purposes; a detection method was subsequently developed and validated in accordance to conventional screening protocols based on enzymatic hydrolysis, liquid‐liquid extraction, and liquid chromatography/electrospray tandem mass spectrometry analysis. The method was applied to approximately 7500 urine doping control samples yielding two JWH‐018 findings and demonstrated its capability for a sensitive and selective identification of JWH‐018 and its metabolites in human urine. Copyright © 2010 John Wiley & Sons, Ltd.
Tập 3 Số 9 - Trang 609-620 - 2011
Sewage‐based epidemiology in monitoring the use of new psychoactive substances: Validation and application of an analytical method using LC‐MS/MS 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.
Tập 7 Số 9 - Trang 812-818 - 2015
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 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.
Tập 8 Số 1 - Trang 63-70 - 2016
#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
Report on a novel emerging class of highly potent benzimidazole NPS opioids: Chemical and in vitro functional characterization of isotonitazene Abstract This paper reports on the identification and full chemical characterization of isotonitazene (N ,N ‐diethyl‐2‐[5‐nitro‐2‐({4‐[(propan‐2‐yl)oxy]phenyl}methyl)‐1H‐benzimidazol‐1‐yl]ethan‐1‐amine), a potent NPS opioid and the first member of the benzimidazole class of compounds to be available on online markets. Interestingly, this compound was sold under the name etonitazene, a structural analog. Identification of isotonitazene was performed by gas chromatography mass spectrometry (GC–MS) and liquid chromatography time‐of‐flight mass spectrometry (LC‐QTOF‐MS), the latter identifying an exact‐mass m/z value of 411.2398. All chromatographic data indicated the presence of a single, highly pure compound. Confirmation of the specific benzimidazole regio‐isomer was performed using 1 H and 13 C NMR spectroscopy, after which the chemical characterization was finalized by recording Fourier‐transform (FT‐IR) spectra. A live cell‐based reporter assay to assess the in vitro biological activity at the μ‐opioid receptor (MOR) revealed that isotonitazene has a high potency (EC50 of 11.1 nM) and efficacy (Emax 180% of that of hydromorphone), thus confirming that this substance is a strong opioid. Isotonitazene has not been previously detected, either in powder form, or in biological fluids. The high potency and efficacy of isotonitazene, combined with the fact that this compound was being sold undiluted, represents an imminent danger to anyone aiming to use this powder.
Tập 12 Số 4 - Trang 422-430 - 2020
<i>In vitro</i> and <i>in vivo</i> human metabolism of the synthetic cannabinoid AB‐CHMINACA 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.
Tập 7 Số 10 - Trang 866-876 - 2015
The detection of the urinary metabolites of 3‐[(adamantan‐1‐yl)carbonyl]‐1‐pentylindole (AB‐001), a novel cannabimimetic, by gas chromatography‐mass spectrometry 3‐[(Adamantan‐1‐yl)carbonyl]‐1‐pentylindole (AB‐001), a synthetic cannabimimetic, was identified in head shop products in Ireland in 2010. German authorities also reported it to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) via the Early Warning System (EWS) in 2011. As indole‐derived cannabimimetics, such as JWH‐018, JWH‐073, and JWH‐250, undergo extensive metabolism, it was expected that AB‐001 would behave similarly. To include it in our toxicological screening protocols, we have identified its urinary metabolites in humans following oral administration. The major metabolites were found to be adamantane mono‐hydroxylated and adamantane mono‐hydroxylated/N ‐dealkylated products. No parent compound was found in urine, and metabolites were detectable for up to 160 h following administration. Copyright © 2011 John Wiley & Sons, Ltd.
Tập 4 Số 6 - Trang 519-524 - 2012
Prevalence of new psychoactive substances and prescription drugs in the Belgian driving under the influence of drugs population 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.
Tập 10 Số 3 - Trang 539-547 - 2018