合成大麻素类物质合成方法和制毒物品分析

合成大麻素是数量最多，化学结构多样的一大类新精神活性物质。本文综述了合成大麻素类物质的化学结构和合成方法，分析了合成大麻素类物质相关制毒物品并提出了管控对策，以期从源头上降低合成大麻素类物质的危害。     

利用高分辨液质联用仪检测新型合成大麻素

目的介绍一种鉴别非法合成大麻素(AMB-FUBINACA)结构的方法。方法巧用GC-MS质谱谱库检索提示信息,利用高分辨液质联用仪的一级质谱碎片推导的分子式与GC-MS的质谱谱库检索物质的分子式进行比较,推测目标物的结构式。目标物的结构式符合液质联用仪(LC-MS/MS)的二级质谱碎片(误差4×10-7)和GC-MS的质谱碎片归属,并结合文献报道进行综合研判。结果对一例网络售卖合成大麻素的案件进行了检验,准确判定缴获样品“小树枝”中含有的合成大麻素为AMB-FUBINACA。结论该方法可为解析一些未知物的结构提供新途径。     

合成大麻素类新精神活性物质的代谢物鉴定研究进展

合成大麻素类是目前涵盖物质种类最多、滥用最为严重的一类新精神活性物质,代谢物鉴定研究可以为合成大麻素滥用监测提供基础数据,是目前的研究热点。合成大麻素结构修饰的主要趋势是戊基吲哚或吲唑环戊基末端上的氟原子取代为氢原子,这大大提高了化合物的生物活性,涉及的主要代谢反应包括羟基化、氧化脱氟、酰胺水解、酯水解。液相色谱-高分辨质谱已成为代谢物结构鉴定的首选方法。本文基于合成大麻素的结构和分类,着重对代谢软件预测以及人肝细胞模型、人肝微粒体模型、大鼠体内模型、斑马鱼模型和真菌秀丽线虫模型在代谢物鉴定方面的研究进展进行综述。     

疑似毒品烟丝和烟油中检出新型合成大麻素ADB-BUTINACA

正近几年,新型合成大麻素类毒品在我国广泛传播,目前相关文献已经报道了ADB-FUBINACA、5F-MDMB-PICA、AMB-FUBINACA等诸多新型合成大麻素类毒品案件~([1-4])。截止2021年4月15日,Cayman上已列出合成大麻素类化合物794种,远超芬太尼类毒品的398种。本文利用GC/MS和LC/MS/MS在山东省缴获的疑似毒品烟叶和陕西省缴获的烟油中同时检出一种新型合成大麻素:ADB-BUTINACA。我国已经列管了53种合成大麻素~([5]),     

可疑植物制品中合成大麻素5F-EDMB-PICA的鉴定

目的探讨无对照品时可疑植物制品中未知合成大麻素的定性分析策略。方法采用甲醇对植物制品中的合成大麻素进行提取,提取液经旋转蒸发仪浓缩后采用制备液相分离、纯化,得到高纯度合成大麻素制备样品,综合利用气相色谱-质谱法(gas chromatography-mass spectrometry,GC-MS)、超高效液相色谱-四极杆飞行时间质谱(ultra-high performance liquid chromatography-quadrupole time-of-flight massspectrometry,UPLC-QTOF-MS)、核磁共振(nuclear magnetic resonance,NMR)对制备化合物进行结构解析。结果采用制备液相得到10 mg高纯度未知样品,采用GC-MS、UPLC-QTOF-MS和NMR进行分析,通过谱图解析,最终确定未知合成大麻素为2-[1-(5-氟戊基)-1H-吲哚-3-甲酰氨基]-3,3-二甲基丁酸乙酯,简称5F-EDMB-PICA。结论本研究建立了采用制备液相从低含量植物制品中提取未知合成大麻素的方法,并综合利用GC-MS、UPLC-QTOF-MS、NMR实现了对未知物结构的解析,这些信息将有助于法庭科学实验室在鉴定实践中鉴定该物质或其他具有类似结构的化合物。     

缴获疑似毒品烟叶检出新型合成大麻素1例

随着互联网的发展,全球范围内的科技交流更为快捷。与此同时,制毒技术也在互联网上蔓延。为了逃避打击处理,不法分子通过在被管制毒品分子基础上增减、变换取代基位置、改变取代基结构等方式,合成一系列与管制毒品结构相似的新型毒品,合成大麻素是其中的一类[1]。自2013年起,我国开始对合成大麻素类毒品进行管制。     

电子烟油中新型合成大麻素检测分析

正新精神活性物质(New Psychoactive Substances),也称为"策划药"~([1])。合成大麻素作为一类增长最快的新精神活性物质。法医学分析中,最常用的是气相色谱-质谱仪(GC-EI-MS),它可以快速、准确推测合成大麻素的结构。本文通过对两批次烟油进行了GC-EI-MS分析,均检测出同一种新型合成大麻素:3,3-二甲基-2-[1-(4-氟丁基)吲哚-3-甲酰胺基]丁酸甲酯(4F-MDMB-BICA)。4F-MDMB-BICA与4F-MDMB-BINACA结构非常相似,它们的结构及EI(70eV)裂解裂解方式见图1。     

可疑电子烟油中5种吲哚或吲唑酰胺类合成大麻素的GC-MS定性和定量分析

目的 建立可疑电子烟油样品中合成大麻素及其主要基质、添加物的GC-MS定性定量分析方法。方法 电子烟油样品用甲醇稀释后进行GC-MS分析,以特征碎片离子和保留时间对电子烟油中的合成大麻素及其主要基质、添加物进行定性分析,在选择离子监测模式下对合成大麻素进行定量分析。结果GC-MS定量方法中各化合物的线性范围为0.025～1 mg/mL,基质加标回收率为94%～103%,日内精密度相对标准偏差小于2.5%,日间精密度相对标准偏差小于4.0%。在25份电子烟油样品中检出了5种吲哚或吲唑酰胺类合成大麻素类物质。电子烟油的基质主要为丙二醇、丙三醇,部分样品中还检出了N,2,3-三甲基-2-异丙基丁酰胺、三乙酸甘油酯和尼古丁等添加物。25份电子烟油样品中合成大麻素的含量范围为0.05%～2.74%。结论 所建立的电子烟油样品中合成大麻素、基质、添加物的GC-MS方法选择性好、分离度高、检出限低,可用于多组分同时定性和定量分析;所探讨的吲哚或吲唑酰胺类化合物的电子轰击离子源碎片离子碎裂机制有助于鉴定该类物质或其他具有类似结构的化合物。     

新型合成大麻素MDMB-4en-PINACA检测1例

<正>近年来,合成大麻素（SCS）物质的滥用在国内日益严重且呈蔓延趋势,由该类物质滥用所导致的恶性案件时有发生。本文报道一起因吸食合成大麻素导致暴力伤害致死案件的电子烟油和吸食者尿液检材中新型合成大麻素MDMB-4en-PINACA的检测案例,系国内首次在吸食者尿液中检出MDMB-4en-PINACA的报道,     

合成大麻素检验方法研究进展

近年合成大麻素类物质(synthetic cannabinoids,SCs)的危害及滥用引起社会广泛关注,它们不仅具有类似天然大麻的致幻性,还有更强的副作用,包括潜在的神经精神毒性,严重影响人类身心健康。因此,国内外研究人员对合成大麻素及其代谢物的检验方法进行了相关研究。本文主要介绍了SCs的生理药理作用、主要分类等,对其检验方法研究进展进行了综述与展望,探讨了各检验方法的应用范围与选择依据,以期为SCs相关案件的检验鉴定提供参考。     

Rapid Identification of Synthetic Cannabinoids in Herbal Incenses with DART‐MS and NMR

The usage of herbal incenses containing synthetic cannabinoids has caused an increase in medical incidents and triggered legislations to ban these products throughout the world. Law enforcement agencies are experiencing sample backlogs due to the variety of the products and the addition of new and still‐legal compounds. In our study, proton nuclear magnetic resonance (NMR) spectroscopy was employed to promptly screen the synthetic cannabinoids after their rapid, direct detection on the herbs and in the powders by direct analysis in real time mass spectrometry (DART‐MS). A simple sample preparation protocol was employed on 50 mg of herbal sample matrices for quick NMR detection. Ten synthetic cannabinoids were discovered in fifteen herbal incenses. The combined DART‐MS and NMR methods can be used to quickly screen synthetic cannabinoids in powder and herbal samples, serving as a complementary approach to conventional GC‐MS or LC‐MS methods.     

Quantitation of Synthetic Cannabinoids in Plant Materials Using High Performance Liquid Chromatography with UV Detection (Validated Method)

Plant based products laced with synthetic cannabinoids have become popular substances of abuse over the last decade. Quantitative analysis for synthetic cannabinoid content in the laced materials is necessary for health hazard assessments addressing overall exposure and toxicity when the products are smoked. A validated, broadly applicable HPLC‐UV method for the determination of synthetic cannabinoids in plant materials is presented, using acetonitrile extraction and separation on a commercial phenylhexyl stationary phase. UV detection provides excellent sensitivity with limits of quantitation (LOQs) less than 10 μg/g for many cannabinoids. The method was validated for several structural classes (dibenzopyrans, cyclohexylphenols, naphthoylindoles, benzoylindoles, phenylacetylindoles, tetramethylcyclopropylindoles) based on spike recovery experiments in multiple plant materials over a wide cannabinoid contents range (0.1–81 mg/g). Average recovery across 32 cannabinoids was 94% for marshmallow leaf, 95% for damiana leaf, and 92% for mullein leaf. The method was applied to a series of case‐related products with determined amounts ranging from 0.2 to >100 mg/g.     

Identification of two cannabimimetic compounds WIN48098 and AM679 in illegal products

Two synthetic cannabinoids have been identified, during a survey, as new adulterants; they might have been intended to be used as ingredients for smart drugs. The characterization of these compounds has been made by gas chromatography–mass spectrometry (GC–MS), Orbitrap high resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR), leading to the identification of WIN48098, a compound disclosed as a new adulterant in herbal and powder products, and AM679, identified in Italy for the first time.Taking into account the high number of synthetic cannabinoids seized during the last year in Italy, how quickly they appear on the illegal market and the rapidity required for analytical results, a method was developed for the simultaneous quantitation of several synthetic cannabinoids, using gas chromatography–flame ionization detection (GC–FID).     

Separation and structural characterization of the synthetic cannabinoids JWH-412 and 1-[(5-fluoropentyl)-1H-indol-3yl]-(4-methylnaphthalen-1-yl)methanone using GC-MS, NMR analysis and a flash chromatography system

The 'herbal highs' market continues to boom. The added synthetic cannabinoids are often exchanged for another one with a high frequency to stay at least one step ahead of legal restrictions. While most of these substances were synthesized for pharmaceutical purposes and have been described in the scientific literature before, others originate from clandestine laboratories supplying this lucrative market. In this paper, the identification and structure elucidation of two synthetic cannabinoids is reported. The first compound, 1-[(5-fluoropentyl)-1H-indol-3yl]-(4-methylnaphthalen-1-yl)methanone, was found along with AM-2201 in a 'herbal mixture' obtained via the Internet. For isolation of the substance from the mixture, a newly developed flash chromatography method was used providing an inexpensive and fast way to gain pure reference substances from 'Spice' products for the timely development or enhancement of analytical methods in the forensic field. The second substance, 4-fluoronaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-412) was seized by German authorities as microcrystalline powder, making it very likely that it will be found in 'herbal mixtures' soon.     

Synthetic cannabinoids in "spice-like" herbal blends: First appearance of JWH-307 and recurrence of JWH-018 on the German market

Herbal smoking blends, available on the German market were analyzed and several known synthetic cannabinoids were identified (JWH-122 and JWH-018). In addition, we isolated a new active ingredient by silica gel column chromatography and elucidated the structure by nuclear magnetic resonance (NMR) methods. The compound was identified as JWH-307, a synthetic cannabinoid of the phenyl-pyrrole subclass with known in vitro binding affinities for cannabinoid receptors. To date, this is the first appearance of this subclass of cannabimimetics in such products. JWH-307 has been further characterized by gas chromatography accurate mass spectrometry (GC-HRMS), electrospray tandem mass spectrometry (ESI-MS/MS), ultraviolet (UV) and infrared (IR) spectroscopy. JWH-018 was among the first compounds banned by many countries world-wide including Germany. The identification of JWH-018 was striking, since this is the first report where JWH-018 recurred on the German market thus violating existing laws. A generic method was established to quantify synthetic cannabinoids in herbal smoking blends. Quantification was achieved using an isotopically labeled standard (JWH-018-D(3)). JWH-018 was found at a level of 150mg/g while JWH-122 and JWH-307 occurred as a mixture at a total level of 232mg/g.     

Near‐fatal Intoxication with the “New” Synthetic Opioid U‐47700: The First Reported Case in the Czech Republic

Recreational use of the potent synthetic opioid 3,4‐ dichloro‐N‐(2‐(dimethylamino)cyclohexyl)‐N‐methylbenzamide (U‐47700) is rising, accompanied by increasingly frequent cases of serious intoxication. This article reports a case of near‐fatal U‐47700 intoxication. A man was found unconscious (with drug powder residues). After 40 h in hospital (including 12 h of supported ventilation), he recovered and was discharged. Liquid chromatography/high‐resolution mass spectrometry (LC/HRMS) or gas chromatography/mass spectrometry (GC/MS) were used to detect and quantify substances in powders, serum and urine. Powders contained U‐47700 and two synthetic cannabinoids. Serum and urine were positive for U‐47700 (351.0 ng/mL), citalopram (<LOQ), tetrahydrocannabinol (THC: 3.3 ng/mL), midazolam (<LOQ) and a novel benzodiazepine, clonazolam (6.8 ng/mL) and their metabolites but negative for synthetic cannabinoids. If potent synthetic opioids become cheaper and more easily obtainable than their classical counterparts (e.g., heroin), they will inevitably replace them and users may be exposed to elevated risks of addiction and overdose.     

DART‐MS as a Preliminary Screening Method for “Herbal Incense”: Chemical Analysis of Synthetic Cannabinoids

Direct analysis in real time mass spectrometry (DART‐MS) served as a method for rapid high‐throughput screening of six commercially available “Spice” products, detecting various combinations of five synthetic cannabinoids. Direct analysis in real time is an ambient ionization process that, along with high mass accuracy time‐of‐flight (TOF)‐MS to 0.0001 Da, was employed to establish the presence of cannabinoids. Mass spectra were acquired by simply suspending a small portion of sample between the ion source and the mass spectrometer inlet. The ability to test minute amounts of sample is a major advantage when very limited amounts of evidentiary material are available. In addition, reports are widespread regarding the testing backlogs that now exist because of the large influx of designer drugs. This method circumvents time‐consuming sample extraction, derivatization, chromatographic, and other sample preparative steps required for analysis by more conventional mass spectrometric methods. Accordingly, the synthetic cannabinoids AM‐2201, JWH‐122, JWH‐203, JWH‐210, and RCS‐4 were identified in commercially available herbal Spice products, singly and in tandem, at concentrations within the range of 4–141 mg/g of material. Direct analysis in real time mass spectrometry decreases the time necessary to triage analytical evidence, and therefore, it has the potential to contribute to backlog reduction and more timely criminal prosecution.     

Identification of Eight Synthetic Cannabinoids,Including 5F‐AKB48 in Seized Herbal Products Using DART‐TOF‐MS and LC‐QTOF‐MS as Nontargeted Screening Methods

Synthetic cannabinoids are sprayed onto plant material and smoked for their marijuana‐like effects. Clandestine manufacturers modify synthetic cannabinoid structures by creating closely related analogs. Forensic laboratories are tasked with detection of these analog compounds, but targeted analytical methods are often thwarted by the structural modifications. Here, direct analysis in real time coupled to accurate mass time‐of‐flight mass spectrometry (DART‐TOF‐MS) in combination with liquid chromatography quadruple time‐of‐flight mass spectrometry (LC‐QTOF‐MS) are presented as a screening and nontargeted confirmation method, respectively. Methanol extracts of herbal material were run using both methods. Spectral data from four different herbal products were evaluated by comparing fragmentation pattern, accurate mass and retention time to available reference standards. JWH‐018, JWH‐019, AM2201, JWH‐122, 5F‐AKB48, AKB48‐N‐(4‐pentenyl) analog, UR144, and XLR11 were identified in the products. Results demonstrate that DART‐TOF‐MS affords a useful approach for rapid screening of herbal products for the presence and identification of synthetic cannabinoids.     

Effects of synthetic cannabinoids on electroencephalogram power spectra in rats

Several synthetic cannabinoids have recently been distributed as psychoactive adulterants in many herbal products on the illegal drug market around the world. However, there is little information on pharmacology and toxicology of such compounds. Although Δ(9)-tetrahydrocannabinol (Δ(9)-THC), a psychoactive cannabinoid of marijuana, was reported to affect electroencephalograms (EEG) of rats, the effects of synthetic cannabinoids are unknown. We examined the pharmacological activities of three synthetic cannabinoids; cannabicyclohexanol (CCH), CP-47,497 and JWH-018; by analyzing EEG power spectra and locomotor activity after intraperitoneal administration to rats and compared them with those of Δ(9)-THC. The three compounds significantly increased the EEG power in the frequency range of 5.0-6.0 Hz for the first 3h, while Δ(9)-THC decreased the power spectra in the wide range of 7.0-20.0 Hz during the first hour. These results indicate that the effect of the three compounds on EEG is different from that of Δ(9)-THC. Additionally, CCH, CP-47,497 and JWH-018 significantly decreased the locomotor activity for 11.5h, 11h and 4.5h, respectively, after administration which was longer than that of Δ(9)-THC (3.5h). Furthermore, all three compounds significantly reduced the total amounts of locomotor activity during a 3-h, 6-h and 12-h period after injection, whereas no statistical difference was observed for the Δ(9)-THC injection. Among the three compounds, CCH and CP-47,497 exerted a longer duration of the change in the EEG power spectra and suppression of the locomotor activity than JWH-018.