Chiral separation of 3,4-methylenedioxymeth- amphetamine and related compounds in clandestine tablets and urine samples by capillary electrophoresis/fluorescence spectroscopy

The R-(-)- and S-(+)-isomers of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA) were prepared, identified by gas chromatography/mass spectrometry (GC/MS) and then used as standards in a series of capillary electrophoresis (CE) experiments. Using these R-(-)- and S-(+)-isomers, the distribution of (RS)-MDA and (RS)-MDMA stereoisomers in clandestine tablets and suspect urine samples were identified. Several electrophoretic parameters, such as the concentration of beta-cyclodextrin used in the electrophoretic separation and the amount of organic solvents required for the separation, were optimized.     

Impurity profiling of seized MDMA tablets by capillary gas chromatography

Impurity profiles of 3,4-methylenedioxymethylamphetamine (MDMA) tablets seized in France have been examined. The samples were extracted with methylene chloride under basic conditions and then analyzed by capillary gas chromatography. Almost 30 compounds were identified as precursors, intermediates and by-products. Palmitic and stearic acid were also found as tableting materials. The comparison of the different profiles obtained by the reported procedure provided very useful information about the synthetic processes used by clandestine laboratories and enabled a classification into several groups of profiles. According to these results, the reductive amination route appears to be the most common synthetic pathway in Western Europe. Furthermore, 3,4-methylenedioxyphenyl-2-propanone seems to be the most used precursor in clandestine laboratories.     

<Superscript>15</Superscript>N isotopic analyses: a powerful tool to establish links between seized 3,4-methylenedioxymethamphetamine (MDMA) tablets

In this study the (15)N/(14)N isotopic ratios of 43 samples of 3,4-methylenedioxymethamphetamine (MDMA) samples were measured using Gas Chromatography-Combustion-Isotope-Ratio Mass Spectrometry (GC-C-IRMS). The results show a large discrimination between samples with a range of delta(15)N values between -16 and +19 per thousand. Comparison between delta(15)N values and other physical and chemical parameters shows a strong relationship between delta(15)N and brand logo or composition. Thus, it could be assumed that tablets from different seizures probably originated from the same clandestine manufacturing source. Hence, (15)N isotopic parameters provide an important additional tool to establish common origins between seizures of clandestine synthetic drugs.     

Application of SERS spectroscopy to the identification of (3,4-methylenedioxy)amphetamine in forensic samples utilizing matrix stabilized silver halides.

A method based on surface-enhanced Raman scattering (SERS) spectroscopy was developed to meet the need for the reliable and rapid identification of illicit drugs such as the 'designer drug' XTC, preferably to increase the security of legal certificates. A matrix stabilized silver halide dispersion on a microtiter plate is used as the SERS-active substrate, providing an easy to use system for sample preparation and probing by means of a Raman microscope. The potential of the method is demonstrated by applying it to the identification of the psychoactive ingredients of drug containing tablets which were confiscated by the local police at techno-music events. The samples of interest were 26 different brands of XTC tablets and several pieces of evidence (powders) containing amphetamine. For reference, we show SERS and Raman spectra of pristine amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethamphetamine.     

解析电喷雾质谱法对感冒药中对乙酰氨基酚的快速检测

基于常压质谱的直接、快速、无需样品预处理检测的优势,该文拓展了其在药物质检领域的应用。采用自行搭建的解析电喷雾(DESI)装置,对常用感冒药对乙酰氨基酚片进行快速质谱检测,无需样品预处理,直接获得药片中有效成分的分子结构信息。为克服基质差异对定量分析的影响,以淀粉为基质构建对乙酰氨基酚模拟药片,在优化的基础上进行定量实验。针对实际药片中高浓度对乙酰氨基酚检测的需要,研究了其在较高浓度范围的定量关系,结果显示,方法对0.35~4.52 mg/mm^2范围内的对乙酰氨基酚具有较好的线性关系(r^2=0.9982),定量下限为1.903 ng/mm^2,检出限为0.237 ng/mm^2,加标回收率为102%~114%。对3种市售的对乙酰氨基酚片进行直接检测,与厂家提供的标准数据相比,相对标准偏差(RSD)为7.2%~12%,表明方法具有较好准确度。该工作很好地证明了DESI-MS在药品快检中的优势,从而为药品质检提供了潜在的高效、可靠的检测手段。     

Chromatographic and spectroscopic methods of identification for the side-chain regioisomers of 3,4-methylenedioxyphenethylamines related to MDEA,MDMMA, and MBDB

Three regioisomeric 3,4-methylenedioxyphenethylamines having the same molecular weight and major mass spectral fragments of equivalent mass have been reported as components of clandestine drug samples in recent years. These drugs of abuse are 3,4-methylenedioxy-N-ethylamphetamine, 3,4-methylenedioxy-N,N-dimethylamphetamine, and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine. These three compounds are a subset of a total of ten regioisomeric 3,4-methylenedioxyphenethylamines of molecular weight 207, yielding regioisomeric fragment ions of equivalent mass (m/z 72 and 135/136) in the electron impact mass spectrum. The specific identification of one of these compounds in a forensic drug sample depends upon the analyst's ability to eliminate the other regioisomers as possible interfering or coeluting substances. This paper reports the synthesis, mass spectral characterization, and chromatographic analysis of these ten unique regioisomers. The ten regioisomeric methylenedioxyphenethylamines are synthesized from commercially available precursor chemicals. The electron impact mass spectra of these regioisomers show some variation in the relative intensity of the major ions with only one or two minor ions that might be considered side-chain specific fragments. Thus, the ultimate identification of any one of these amines with the elimination of the other nine regioisomeric substances depends heavily upon chromatographic methods. Chromatographic separation of these ten uniquely regioisomeric amines is studied using gas chromatographic temperature program optimization.     

调控微波等离子体能量进行药片活性分子结构的质谱分析

采用微波等离子体质谱(MPT-MS)技术,对替硝唑和马来酸氯苯那敏药片进行快速质谱分析.通过调控等离子体能量,在一级谱图中可得到目标物的准分子离子及丰富的碎片离子,这些碎片离子与其对应串联质谱数据基本一致,甚至更加丰富;结合标准品比对分析,最终确定这些碎片离子来自目标物而非基质.因此,MPT兼具硬电离和软电离性质,采用MPT-MS技术从一级质谱图中获得的数据可对药片中活性分子的结构进行鉴定.该方法具有快速、准确及环保等特点,在发展MPT与简单的质量分析器联用,实现质谱仪的小型化等方面有广阔的应用前景.     

Desorption electrospray ionization mass spectrometry: direct toxicological screening and analysis of illicit Ecstasy tablets

Desorption electrospray ionization mass spectrometry (DESI-MS) was used as a simple and rapid way to analyze drug tablets and powders without sample preparation. Experiments were performed with a home-made DESI source coupled to a triple-quadrupole linear-ion trap (QqQ(LIT)) mass spectrometer. Twenty-one commercial drugs as well as some illicit Ecstasy tablets and powders were analyzed. MS spectra almost exclusively showed the protonated or deprotonated ion of the drug after directing the pneumatically assisted electrospray onto the tablet's surface. With some tablets, inhomogeneity of the surface resulted in different spectra depending on the spot analyzed, thus showing that DESI could be used for imaging. Directly triggered MS/MS spectra were used for confirmatory analysis, with analysis times often below 10 s per tablet. For illicit Ecstasy tablets, DESI-MS, GC/MS and LC/MS analyses provided similar qualitative results for the main analytes. With MS/MS spectra library comparison or exact mass measurements, this technique could become very powerful for the rapid analysis of unknown tablets and shows the great potential of desorption techniques as an alternative to solution-based analysis.     

Study on the bioavailability of puerarin from Pueraria lobata isoflavone self-microemulsifying drug-delivery systems and tablets in rabbits by liquid chromatography-mass spectrometry

To evaluate the bioavailability of puerarin from Pueraria lobata isoflavone self-microemulsifying drug delivery systems (SMEDDS) and Yufengningxin tablets, a rapid and specific liquid chromatography--mass spectrometric method was developed and validated to determine puerarin in rabbit serum. The analyte was extracted from serum samples by precipitating the serum proteins, separated on a Diamonsil C(18) column and detected by mass spectrometry with an electrospray ionization interface. 4-Hydroxybenzaldehyde was used as the internal standard. The method has a limit of quantitation of 10 ng/mL using 200 microL serum. The intra-day relative standard deviations (RSDs) ranged from 3.7 to 6.9% and inter-day RSDs were within 6.5%. After administration of SMEDDS and tablets to rabbits, a significant difference was observed in main pharmacokinetic parameters of t(max), C(max) and AUC(0--infinity) between SMEDDS and tablets, and a 2.2-fold increase in the relative bioavailability of puerarin was observed with the SMEDDS compared with Yufengningxin tablets. It was concluded that the absorption of puerarin from Pueraria lobata isoflavone SMEDDS was enhanced.     

Chemical profile of meta-chlorophenylpiperazine (m-CPP) in ecstasy tablets by easy ambient sonic-spray ionization, X-ray fluorescence, ion mobility mass spectrometry and NMR

Meta-chlorophenylpiperazine (m-CPP) is a new illicit drug that has been sold as ecstasy tablets. Easy ambient sonic-spray ionization mass spectrometry (EASI-MS) and X-ray fluorescence spectrometry (XRF) are shown to provide relatively simple and selective screening tools to distinguish m-CPP tablets from tablets containing amphetamines (mainly 3,4-methylenedioxymethamphetamine (MDMA)). EASI-MS detects the active ingredients in their protonated forms: [m-CPP + H](+) of m/z 197, [MDMA + H](+) of m/z 194, and [2MDMA + HCl + H](+) of m/z 423 and other ions from excipients directly on the tablet surface, providing distinct chemical fingerprints. XRF identifies Cl, K, Ca, Fe, and Cu as inorganic ingredients present in the m-CPP tablets. In contrast, higher Cl concentrations and a more diverse set of elements (P, Cl, Ca, Fe, Cu, Zn, Pt, V, Hf, Ti, Pt, and Zr) were found in MDMA tablets. Principal component analysis applied to XRF data arranged samples in three groups: m-CPP tablets (four samples), MDMA tablets (twenty three samples), and tablets with no active ingredients (three samples). The EASI-MS and XRF techniques were also evaluated to quantify m-CPP in ecstasy tablets, with concentrations ranging from 4 to 40 mg of m-CPP per tablets. The m-CPP could only be differentiated from its isomers (o-CPP and for the three isomers p-CPP) by traveling wave ion mobility mass spectrometry and NMR measurements.     

Validation of an HPLC method for quantitation of MDMA in tablets

An isocratic reversed-phase high-performance liquid chromatography (HPLC) method is developed and validated for the quantitation of 3,4-methylenedioxymethamphetamine (MDMA) in tablets. The chromatographic separation is achieved with potassium phosphate buffer (pH 3.2)-acetonitrile (9:1, v/v) as mobile phase, a Chromspher B column, and UV detection at 210 nm. The calibration curve is linear from 1.4 to 111 microg/mL. The percent relative standard deviation for intra- and interday precision studies is 2.7% each. The measurement uncertainty is estimated to 9%. The method is specific and successfully used for routine quantitation of MDMA in tablets.     

Determination of paramethoxyamphetamine and other amphetamine-related designer drugs by liquid chromatography/sonic spray ionization mass spectrometry

Paramethoxyamphetamine (PMA) is an amphetamine-like designer drug that has emerged recently on the European illicit drug market. This drug has a wicked reputation, as a number of lethal intoxications have occurred. A method using high-performance liquid chromatography coupled to ion trap based mass spectrometry (LC/MS) is described for the determination of this compound together with 3,4-methylenedioxymethamphetamine (XTC or MDMA), amphetamine and 3,4-methylenedioxyamphetamine (MDA) in human matrices. A liquid/liquid extraction (LLE) was applied to whole blood, urine and postmortem tissues. Reversed-phase liquid chromatography was performed on a narrow-bore phenyl-type column at a flow rate of 0.3 mL/min. A switch box allowed disposal of early-eluting irrelevant material to waste, protecting the mass spectrometer from contamination. The column effluent was directed into an ion trap mass spectrometer by a sonic spray ionization (SSI) interface. The method was validated for all three matrices, proving the applicability of SSI even when dealing with complex biological matrices. The within-and between-day precisions were less than 17.5% and accuracy was below 16.2%. Weighted (1/x) quadratic calibration curves were generated ranging from 10 to 1000 ng/mL (blood and urine) or 20 to 2000 ng/g (tissue) and correlation coefficients (r(2)) always exceeded 0.995. In addition, the mass spectrum of PMA is given together with a proposed fragmentation pattern for the obtained LC/MS spectrum. This information can be useful for future identification of PMA with LC/MS in biological matrices as well as in confiscated powders or tablets.     

Analysis of ecstasy with a monolithic reversed-phase column

Summary A new, rapid, and precise liquid chromatographic method has been developed for simultaneous identification and quantification of amphetamine,N-methyl-3,4-methylenedioxymetamphetamine,N-ethyl-3,4-methylenedioxymetamphetamine, andN-methyl-1-(3,4-methyl-enedioxyphenyl)-2-butanamine in the presence of other constituents. The compounds were separated on a monolithic column with a gradient prepared from acetonitrile and 20mm monobasic potassium buffer at a flow rate of 1.5 mL min⁻¹. Quantitation was performed with metoclopramide as internal standard. Use of different flow rates was investigated and enabled reduction of the separation time from 11 to 3.5 min for seven substances. The method was then applied to ten seized tablets to identify and quantify their active ingredients.     

超声液相萃取-GC/MS-SIM法定量检测唾液中苯丙胺类毒品

建立了一种人体唾液中苯丙胺(AM)、甲基苯丙胺(MAM)、 3, 4-亚甲二氧基苯丙胺(MDA)、 3, 4-亚甲二氧基甲基苯丙胺(MDMA)毒品的超声波液液萃取-气相色谱/质谱-选择离子检测方法. 对萃取溶剂、萃取时间等参数进行了考查, 确定了乙酸乙酯为萃取溶剂, 在超声波下液液萃取2 min. 用该溶剂对添加毒品的唾液进行提取, 采用气相色谱/质谱-选择离子检测法(GC/MS-SIM)检测, 获得了良好线性, 相对标准偏差在15%内, 准确性均在80%～115%之间, 最小检测限可达0.05 μg/mL. 该方法未对毒品进行衍生化处理, 可用于缴获毒品及嫌疑吸毒者人体生物检材中苯丙胺类毒品的分析.     

Rapid analysis of controlled substances using desorption electrospray ionization mass spectrometry

The recently developed technique of desorption electrospray ionization (DESI) has been applied to the rapid analysis of controlled substances. Experiments have been performed using a commercial ThermoFinnigan LCQ Advantage MAX ion-trap mass spectrometer with limited modifications. Results from the ambient sampling of licit and illicit tablets demonstrate the ability of the DESI technique to detect the main active ingredient(s) or controlled substance(s), even in the presence of other higher-concentration components. Full-scan mass spectrometry data provide preliminary identification by molecular weight determination, while rapid analysis using the tandem mass spectrometry (MS/MS) mode provides fragmentation data which, when compared to the laboratory-generated ESI-MS/MS spectral library, provide structural information and final identification of the active ingredient(s). The consecutive analysis of tablets containing different active components indicates there is no cross-contamination or interference from tablet to tablet, demonstrating the reliability of the DESI technique for rapid sampling (one tablet/min or better). Active ingredients have been detected for tablets in which the active component represents less than 1% of the total tablet weight, demonstrating the sensitivity of the technique. The real-time sampling of cannabis plant material is also presented.     

Simultaneous analysis of synthetic cannabinoids in the materials seized during drug trafficking using GC-MS

A rapid and simple gas chromatography–mass spectrometry (GC-MS) method was developed and validated to identify and quantify synthetic cannabinoids in the materials seized during drug trafficking. Accuracy and reproducibility of the method were improved by using deuterated JWH-018 and JWH-073 as internal standards. Validation results of the GC-MS method showed that it was suitable for simultaneous qualitative and quantitative analyses of synthetic cannabinoids, and we analyzed synthetic cannabinoids in seized materials using the validated GC-MS method. As a result of the analysis, ten species of synthetic cannabinoids were identified in dried leaves (n?=?40), bulk powders (n?=?6), and tablets (n?=?14) seized in Korea during 2009–2012, as a single ingredient or as a mixture with other active co-ingredients. JWH-018 and JWH-073 were the most frequently identified compounds in the seized materials. Synthetic cannabinoids in the dried leaves showed broad concentration ranges, which may cause unexpected toxicity to abusers. The bulk powders were considered as raw materials used to prepare legal highs, and they contained single ingredient of JWH-073, JWH-019, or JWH-250 with the purity over 70 %. In contrast, JWH-018 and JWH-073 contents in the tablets were 7.1–13.8 and 3.0–10.2 mg/g, respectively. Relatively low contents in the tablets suggest that the synthetic cannabinoids may have been added to the tablets as supplements to other active co-ingredients.     

The metabolite profiling of 3,4-dicaffeoylquinic acid in Sprague–Dawley rats using ultra-high performance liquid chromatography equipped with linear ion trap-Orbitrap MS

3,4-Dicaffeoylquinic acid (3,4-DiCQA) is a dicaffeoylquinic acid that possesses antioxidant, anti-inflammatory, antibacterial, antiviral, anticancer, hypoglycemic, hypotensive, and hepatoprotective activities. This study developed a rapid and reliable method using ultra-high performance liquid chromatography equipped with linear ion trap-Orbitrap MS to identify the metabolites of 3,4-DiCQA in rat plasma, urine, feces, and tissues. The metabolic profile of 3,4-DiCQA was determined after an oral administration of 200 mg/kg to rats. A strategy of full scan-parent ions list acquisition coupled to diagnostic product ion analysis for screening and identification of target metabolites was used. A total of 67 metabolites, combined with accurate mass measurement, diagnostic ions, neutral losses, and reference standards, were observed and characterized for the first time. The results indicated that hydrolysis, methylation, hydrogenation, hydration, dehydroxylation, dehydrogenation, sulfate conjugation, and glucuronide conjugation were the major metabolic reactions of 3,4-DiCQA in vivo.     

Improved stability of OPALMON tablets under humid conditions. III: Application of the rotary vacuum drying method to dry Opalmon tablets

In stability studies on moisture-resistant Opalmon tablets in press-through-packages (PTP), which were placed in aluminum bags, we found that the degradation rate of the dextran formulation is faster than that of the lactose formulation. The fast degradation of the dextran formulation is attributed to residual moisture in the package because drying the tablets before packaging suppressed the degradation and there is a good correlation between the stability of the drug and the water-activity of the tablets. Therefore, we developed a new drying method for the tablets, i.e. the rotary vacuum drying method, and investigated the effects of the operating conditions such as heating temperature, rotation speed, and vacuum degree on the drying time, and the appearance of the tablets. Using the rotary vacuum drying method, the tablets were dried over a short time (30 min) on a mass production scale so that the water activity was less than 0.03. Furthermore, the tablets suffered negligible damage such as breaking and chipping during the drying process. These results indicate that the rotary vacuum drying method is useful for drying tablets on mass production scales.     

高效液相色谱法测定盐酸芬氟拉明及其在片剂中含量

应用高效液相色谱法测定了盐酸芬氟拉明及其片剂的含量,使用２５ｃｍ×０．４６ｃｍｉ．ｄ．分析柱,填充ＨｙｐｅｒｓｉｌＢＤＳＣ１８（５μｍ）,检测波长２６４ｎｍ,流动相为Ｖ（乙腈）∶Ｖ（０．４ｍｏｌ／Ｌ乙酸铵）∶Ｖ（三乙胺）＝３０∶７０∶２。选用咖啡因作内标物,用内标法进行定量测定,在０．１～０．５ｇ／Ｌ范围内呈良好的线性关系,相关系数为０．９９９９。片剂的平均回收率为９９．９８％。方法简单、快速、灵敏度高、重现性好。     

Rapid analysis of illicit drugs by mass spectrometry: results from seizures in Ireland

A gas chromatographic procedure with mass spectrometric detection (GC-MS) was established to determine the principal amphetamines, methylenedioxymethamphetamine (MDMA), methylenedioxyethamphetamine (MDEA) and methylenedioxyamphetamine (MDA), cocaine and pharmacologically active impurities in 'ecstasy' tablets. The procedure was developed and optimised by combining the individual methods for the various drugs of abuse available in the literature into a single GC-MS run. New variants of the main drugs which may appear on the drug scene were also detected, including N-methyl-1-phenylethylamine, a member of a new series of illicit drugs. The method is rapid and has good sensitivity and reproducibility.