Characterization and Differentiation of Geometric Isomers of 3‐methylfentanyl Analogs by Gas Chromatography/Mass Spectrometry,Liquid Chromatography/Mass Spectrometry,and Nuclear Magnetic Resonance Spectroscopy

The cis and trans isomers of 3‐methylfentanyl and its three analogs were chemically synthesized, and these compounds were characterized and differentiated by gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS), and nuclear magnetic resonance (NMR) spectroscopy. The cis and trans isomers of the 3‐methylfentanyl analogs were completely separated by GC/MS. Although the high temperature of the GC injection port caused thermal degradation of β‐hydroxy‐3‐methylfentanyl, the degradation was completely suppressed by trimethylsilyl derivatization. The isomers were also well separated by LC/MS on an octadecylsilyl column with 10 mM ammonium acetate and methanol as the mobile phase. The proton NMR signals were split when the hydrochloride salts of the 3‐methylfentanyl analogs were dissolved in deuterated chloroform because stereoisomers were formed by the coordination of the hydrochloride proton to the nitrogen of the piperidine ring of the 3‐methylfentanyl analogs.     

Application of LC−QTOF/MS for the validation and determination of organic explosive residues on Ionscan® swabs

The identification and confirmation of trace explosive residues along with potential precursors and degradation products require a comprehensive laboratory analysis procedure. This study presents the determination of organic explosives consisting of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 2,4,6-trinitrotoluene (TNT), 2,4,6,N-tetranitro-N-methylaniline (Tetryl), 1,3,5-trinitrobenzene (1,3,5-TNB) and pentaerythritol tetranitrate (PETN) by a high-resolution liquid chromatography quadrupole time-of-flight mass spectrometry (LC−QTOF/MS). The qualitative information including retention time, collision energy, precursor ions, and characteristic fragmentation pattern of each explosive were collected using an atmospheric pressure chemical ionization (APCI) in negative ion mode. The separation efficiency among five compounds was greatly achieved in this study. Four real explosive samples consisting of TNT, RDX, PETN and Tetryl and 12 Ionscan® quality control swabs from the Royal Thai Army were also tested to validate and verify the viability of the GC–MS method used to validate results from an Ionscan® system. The results showed that LC−QTOF/MS is a powerful technique for the identification and confirmation of thermally unstable organic explosives on Ionscan® swabs compared to a conventional GC−MS technique.     

High-performance liquid chromatography-ultraviolet-visible spectroscopy-electrospray ionization mass spectrometry method for acrylic and polyester forensic fiber dye analysis

A critical point of comparison between a fiber collected from a crime scene and a fiber from a known source is the color. Fiber dye analysis using thin-layer chromatography or ultraviolet (UV)-visible (Vis) microspectrophotometry provides useful, although limited, data for comparison. High-performance liquid chromatography-electrospray ionization mass spectrometry (LC/MS) overcomes these limitations by integrating chromatography, ultraviolet-visible spectroscopy, and mass spectrometry into a single instrument. In order to evaluate the applicability of the LC/MS to forensic fiber dye analysis, a multi-stage chromatographic method using acidified water and acidified acetonitrile was developed that separated and identified a mixture of 15 basic and 13 disperse dye standards. The LC/MS also detected and analyzed dyes extracted from individual 0.5 cm acrylic and polyester fibers, demonstrating its applicability to this type of analysis. With regard to the analysis of disperse dyes in polyester fibers, the replacement of pyridine with acetonitrile in the extraction system allowed direct injection of the extracts into the LC/MS. The advantage of the LC/MS over other instrumental methods of textile dye analysis is demonstrated by the analysis and differentiation of three black acrylic fibers: two fibers had similar UV-Vis spectra but were differentiated with chromatography and two had similar UV-Vis spectra and chromatograms but were differentiated using the mass spectrometer.     

4F‐MDMB‐BINACA: A New Synthetic Cannabinoid Widely Implicated in Forensic Casework

This is the first report regarding the characterization of the new synthetic cannabinoid 4F‐MDMB‐BINACA. 4F‐MDMB‐BINACA was first analytically confirmed in seized drug material using gas chromatography–mass spectrometry (GC‐MS), liquid chromatography–quadrupole time‐of‐flight mass spectrometry (LC‐QTOF), and nuclear magnetic resonance (NMR) spectroscopy. Subsequent to this characterization, 4F‐MDMB‐BINACA was detected in biological specimens collected as part of forensically relevant casework, including medicolegal death investigations and drug impaired driving investigations, from a variety of regions in the United States. Further analysis of biological specimens resulted in the identification of the metabolites 4F‐MDMB‐BINACA 3,3‐dimethylbutanoic acid and 4‐OH‐MDMB‐BINACA. 4F‐MDMB‐BINACA is appearing with increasing frequency as a contributory factor in deaths, creating morbidity and mortality risks for drug users. Laboratories must be aware of its presence and impact, incorporating 4F‐MDMB‐BINACA into workflows for detection and confirmation.     

N-甲基-3,4-亚甲二氧基卡西酮的确证

目的 对毒品案件样本进行N-甲基-3,4-亚甲二氧基卡西酮(bk-MDMA)确证检验.方法 采用阴离子检测、颜色反应、气质联用(GC/MS)、核磁共振(NMR)、傅立叶变换红外光谱(FTIR)等方法对毒品案件中白色晶体样本进行剖析确证.结果 快速筛查结果提示样本为具有亚甲二氧基结构的仲胺物质的盐酸盐,经GC/MS、NMR、FTIR检验,确证样本为bk-MDMA,系3,4-亚甲二氧基甲基苯丙胺(3,4-methylenedioxymethamphetmaine,MDMA)的卡西酮类似物.结论 采用本文所用方法可以对毒品案件样本中N-甲基-3,4-亚甲二氧基卡西酮成分进行确证,该药具有滥用的可能性应引起相关部门的重视.     

Differentiation of side chain isomers of ring-substituted amphetamines using gas chromatography/infrared/mass spectrometry (GC/IR/MS).

Common analytical methods used for identifying samples obtained from clandestine laboratories were evaluated for their ability to differentiate between possible amphetamine isomers and homologs. A series of ring-substituted (4-methyl, 4-methoxy, and 3,4-methylenedioxy) amphetamine and N-methylphenethylamine isomers was analyzed using color tests, thin-layer chromatography, gas chromatography/mass spectrometry (GC/MS) and GC/infrared (GC/IR). The N-acetyl derivatives of the isomers were analyzed using GC/IR/MS. GC/IR/MS readily differentiated the 4-methylphenylalkylamine isomers. MS and IR spectra were also obtained for each pair of the 4-methoxyphenylalkylamine isomers and the 3,4-methylenedioxyphenylalkylamine isomers, but differentiation via GC/IR/MS was difficult. The N-acetyl derivatives of each pair of isomers could be readily differentiated using GC/IR/MS. Good library researchable spectra for N-acetylamphetamine could be obtained for IR identification with 10 ng (on-column) and MS identification with 2 ng. The spectrometrically independent IR and MS data obtained for the N-acetyl derivatives indicated that the combination of GC/IR/MS can add a significant level of confidence in the analysis of ring-substituted arylalkylamines.     

The analytical profile of some 4-methylthioamphetamine (4-MTA) homologues

The 4-methylthioamphetamine (4-MTA) is a sulphur-containing amphetamine-type stimulant (ATS), which appeared on the illicit market in Europe at the end of 90s. For the purpose of this study, several N-alkyl homologues of 4-MTA, including 4-methylthiomethamphetamine (4-MTMA), 4-methylthioethylamphetamine (4-MTEA), 4-methylthiodimethamphetamine (4-MTDMA), 4-methylthiopropylamphetamine (4-MTPA) and 4-methylthiobutylamphetamine (4-MTBA) were synthesized. The homologues were characterized by means of gas chromatography/mass spectrometry (GC–MS), infrared (IR) spectroscopy and the magnetic resonance spectroscopy (¹H and ¹³C NMR). The gas chromatography and mass spectrometry properties of their acetyl, trifluoroacyl (TFA), pentafluoropropionyl (PFP) and heptafluorobutyryl (HFB) derivatives were also investigated and discussed.     

Identification of 2‐(ethylamino)‐1‐(4‐methylphenyl)‐1‐pentanone (4‐MEAP), a New “Legal High” Sold by an Internet Vendor as 4‐Methyl Pentedrone

Online vendors are offering a new legal high, 4‐methylpentedrone (4‐MPD). Information for potential users provided by internet vendors of 4‐MPD includes incorrect structures and nonexistent CAS numbers. A sample of 4‐MPD was obtained and analyzed using GC‐MS, NMR, and LC‐EIS. The fragmentation data from the GC‐MS and LC‐EIS produced an M‐1 ion that suggested the molecular mass was 219 amu, rather than 205 amu as calculated for 4‐methylpentedrone. The difference in molecular mass corresponded to the addition of a methyl group. Based on the mass and fragmentation pattern, two standards were synthesized, 2‐(ethylamino)‐1‐(4‐methylphenyl)‐1‐pentanone and 1‐(4‐methylphenyl)‐2‐(propylamino)‐1‐butanone. The synthesis involved bromination of the appropriate ketone followed by the reaction with ethylamine or propylamine. Based on the NMR data and unique fragmentation patterns produced by these molecules, the sample was identified as 2‐(ethylamino)‐1‐(4‐methylphenyl)‐1‐pentanone, not 4‐methylpentedrone.     

Use of Xylazine in Drug‐Facilitated Crimes

Human xylazine poisoning is uncommon. This report describes the use of xylazine for intentional poisoning with criminal intent. Two incidents occurred within 3 weeks: the first involved one victim, and the second involved two victims. The clinical presentations were brief coma, bradycardia, hypotension, and hyperglycemia. The victims recalled having been given a drink from a stranger in a hospital waiting room before loss of consciousness. In the first case, general drug screening by gas chromatography/mass spectrometry (MS) revealed xylazine in the gastric contents, but liquid chromatography–tandem MS (LC‐MS/MS) of serum did not. In the second incident, LC‐MS/MS screening of both victims’ urine and serum samples revealed an unknown peak in the total ion chromatograms, which a molecular mass database identified as morantel or xylazine. The latter was confirmed by comparison with a xylazine standard. Based on this report, we suggest that xylazine should be classified as a controlled drug.     

Quantitative Analysis of Gamma‐Hydroxybutyrate at Endogenous Concentrations in Hair using Liquid Chromatography Tandem Mass Spectrometry

Abstract: A method capable of quantifying endogenous concentrations of gamma‐hydroxybutyrate (GHB) in human head hair was developed and validated using liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). Hair was digested under alkaline conditions, and GHB was isolated using liquid–liquid extraction. LC/MS/MS was performed using atmospheric pressure chemical ionization in the negative mode, multiple reaction monitoring, and deuterated internal standard (GHB‐D₆). Linearity was observed between 0.1 and 100 ng/mg GHB (R² = 1.000). The limits of detection and quantitation in human hair were 0.2 and 0.4 ng/mg, respectively. Accuracy at 2 ng/mg and 10 ng/mg was determined to be 97% and 94%, and intra‐assay CVs at these concentrations were 5.2% and 7.4% (n = 4). Beta‐hydroxybutyrate (BHB), alpha‐hydroxybutyrate, gamma‐butyrolactone, and 1,4‐butanediol did not produce an interference, and there was negligible ion suppression or enhancement from the matrix.     

Morbidity Involving the Hallucinogenic Designer Amines MDA and 2C‐I*

Abstract: A case is presented of a 39‐year‐old woman who suffered severe debilitation because of a hemorrhagic stroke in the context of substance abuse. The patient presented to the emergency room with rapidly diminishing mental status, hypertension, and vasoconstriction; her friends provided a history of ingestion of cocaine, 3,4‐methylenedioxymethamphetamine (MDMA), and 2C‐I, a novel designer amine. A multi‐targeted LC‐MS/MS method for sympathomimetic amines and related drugs in urine detected and quantified 2C‐I and MDA, while ruling out MDMA. The cause of the stroke was determined to be an underlying cerebrovascular abnormality called Moyamoya, secondary to substance abuse. In clinical laboratories, gas chromatography–mass spectrometry or liquid chromatography–tandem mass spectrometry (LC‐MS/MS) confirmation of a positive amphetamine immunoassay is usually directed only towards amphetamine, methamphetamine, MDMA and MDA. This report demonstrates the utility of testing for a wider menu of compounds using LC‐MS/MS in order to better characterize the prevalence and toxicities of novel amines such as 2C‐I.     

GC法和GC/MS法在地区毒品情报分析中的应用

目的探讨气相色谱法(GC)和气相色谱/质谱联用法(GC/MS)在地区毒品情报分析中的应用,并用于实际样品分析。方法采用GC/MS法定性分析毒品样品中的主成分、痕量杂质、掺假剂和稀释剂,并选择GC/FID法和内标标准曲线法定量分析上述各组分,通过定性和定量数据的统计和分析,推断该地区的毒品状况。结果用GC/MS定性分析、GC/FID定量分析,和数据的统计比对,获得了某省某年27起海洛因毒品大案样品主成分、痕量杂质、掺假剂和稀释剂组成及含量的特征,发现该省缴获的大宗海洛因毒品主要以掺假和稀释后的产品出现,且咖啡因和扑热息痛为两种主要的掺假剂和稀释剂。结论GC/MS和GC/FID法在地区毒品情报分析和打击毒品犯罪中可以发挥重要作用。     

Detection of Cutting Agents in Drug‐Positive Seized Exhibits within the United States

The following report summarizes a study performed on seized drug exhibits collected in two U.S. states to evaluate the presence and identification of cutting agents. Aliquots of seized drug materials from Kentucky (n = 200) and Vermont (n = 315) were prepared using a dilute‐and‐shoot procedure. Initial analysis was performed using gas chromatography–mass spectrometry (GC‐MS) followed by analysis using liquid chromatography quadrupole time‐of‐flight mass spectrometry (LC‐QTOF). Active compounds detected overall included caffeine (31.0%), quinine/quinidine (24.7%), levamisole (11.6%), acetaminophen, (8.2%) and procaine (8.2%). These compounds were found with several drugs of abuse, such as heroin, fentanyl, methamphetamine, and cocaine. This novel information about cutting agents used to dilute or alter drugs of abuse is important to criminal investigations and in the management of acute intoxications at health centers. However, common methodologies for analysis and standard reporting practices frequently do not include cutting agents, resulting in lacking or inadequate information regarding prevalence of these substances.     

离子交换柱法萃取血样中4种巴比妥类药物

目的建立血样中4种常见巴比妥类药物的固相萃取方法。方法采用Oasis MAX固相萃取柱对样品进行预处理,以2%氨水淋洗2,%甲酸-甲醇洗脱,GC/NPD定量检验,GC/MS定性检验。结果血样中4种常见巴比妥类药物平均萃取回收率达80%以上,以信噪比10/1计,最小定量限为1～2μg/mL,以信噪比3/1计,检出限为0.5～1μg/mL,在1～50μg/mL范围内,线性相关系数均在0.99以上。结论本文固相萃取方法检出限低,回收率高,选择性强,可应用于血样中4种常见巴比妥类药物的检测。     

Counterfeit Adderall Containing Aceclofenac from Internet Pharmacies

A nontargeted approach based on liquid chromatography equipped with a quadrupole time‐of‐flight mass detector (LC‐MS Q‐TOF) joined to nuclear magnetic resonance (NMR) analysis allowed rapid identification and quantification of the anti‐inflammatory drug aceclofenac in illegal Adderall tablets. The largest chromatographic peak had m/z = 354.030 and m/z = 376.012 matching, respectively, the ionic structures (M + H)⁺ and (M + Na)⁺ of a molecule M. The accurate mass data generated the molecular formula C₁₆H₁₃Cl₂NO₄. A screening of the pharmaceutical active substances having that molecular formula together with the MS/MS fragmentation pattern suggested aceclofenac. Aceclofenac structure was unambiguously confirmed by ¹H and ¹³C NMR experiments. The aceclofenac content was 90 mg/tablet (RSD 2%) as detected by quantitative NMR. Information on the identity and content of illegal drugs is required for legal purposes; it supports in evaluating the effective impact on users safety, and it is useful for control laboratories using a targeted approach in their analytical activities.     

Synthesis and identification of urinary metabolites of 4-iodo-2,5-dimethoxyphenethylamine

This article describes the synthesis and identification of urinary metabolites of 4-iodo-2,5-dimethoxyphenethylamine (2C-I), a new psychoactive drug. 2C-I hydrochloride was administered orally to male Sprague-Dawley rats, and the urinary extracts were analyzed by gas chromatography/mass spectrometry (GC/MS), then five putative 2C-I metabolites were synthesized in our laboratory. In the synthetic process of the 2C-I metabolites, iodination of the aromatic ring was successfully carried out using iodine and orthoperiodic acid as the iodination reagent, and selective debenzylation of aryl benzyl ether was accomplished by the acid hydrolysis method using trifluoroacetic acid and thioanisole. The synthesized metabolites were well separated and detected by GC/MS after valeryl derivatization. The results showed that 2C-I underwent O-demethylation, N-acetylation, and deamination, followed by oxidation to the corresponding carboxylic acid in rats. The data presented in this study will be very useful for the analysis of 2C-I and its metabolites in forensic samples.     

A contribution to the chemical profiling of 3,4-methylenedioxymethamphetamine (MDMA) tablets

A profiling method for the identification of impurities found in seized 3,4-methylenedioxymethamphetamine (MDMA) tablets is presented. Impurities of interest are extracted from an alkaline solution (pH 12.8) by diethyl ether and submitted to gas chromatography (GC)-mass spectrometry (MS) analyses. Identification of impurities is performed by electron impact ionization (Ei) mass spectrometry and confirmation by positive chemical ionization (Ci+) MS or, when possible, MS/MS (MS(2)). Repeat extractions of the same sample give an average relative standard deviation (R.S.D.) of less than 8% within the same day and 15% between days (results were obtained after normalization by the sum of peak areas, each one being acquired by selected ion monitoring (SIM)). Possible application toward batch comparison of samples is discussed. Chromatographic profiles are compared using the cosine function for evaluating similarity and/or dissimilarity among exhibits.     

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.     

Gases released from tissue and analyzed by infrared and gas chromatography/mass spectroscopy techniques

Two techniques for analyzing contaminants released as gases from postmortem tissues were described and compared. One technique used gas chromatography/mass spectrometry (GC/MS); the other, infrared spectroscopy (IR). Brain, lung, liver, blood and urine specimens were obtained from suspected drug-overdose victims whose deaths were contributed to or caused by inhalation of unknown gases or vapors during the period immediately preceding death. Gases from the postmortem tissues and liquid samples were separately admitted into an evacuated IR gas cell, the IR spectra recorded, and gas samples then removed for GC/MS analysis. Nitrous oxide, glue, and paint solvent constituents were identified and measured. Only the brain and lung tissues contained measurable amounts of inhalants. Both IR and GC/MS methods were adequate for normal confirmatory analyses; the GC/MS system was judged superior for fast routine efforts normally hampered by incomplete sample history.     

Development of microwave-assisted extraction procedure for organic impurity profiling of seized 3,4-methylenedioxymethamphetamine (MDMA)

Abstract: Organic impurity profiling of seized 3,4‐methylenedioxymethamphetamine (MDMA) tablets aims to link tablets to common production sources. Conventionally, organic impurities are extracted from tablets using a liquid–liquid extraction (LLE) procedure prior to analysis by gas chromatography–mass spectrometry (GC‐MS). In this research, the development of an alternative microwave‐assisted extraction/headspace solid‐phase microextraction (MAE/HS‐SPME) procedure is described. The optimal procedure used phosphate buffer (1 M, pH 8), with an HS‐SPME extraction temperature of 70°C for 40 min, using a divinylbenzene/Carboxen?/polydimethylsiloxane (DVB/CAR/PDMS) fiber. Impurities were extracted from seized MDMA exhibits using the MAE/HS‐SPME procedure, as well as HS‐SPME alone, and a conventional LLE procedure. The HS‐SPME procedure was deemed to be the most practical because of the affordability and need for less analyst involvement. Although the LLE was limited in the number of impurities extracted, the procedure is still useful for the extraction of less volatile impurities that are not extracted by HS‐SPME.