Optimum methamphetamine profiling with sample preparation by solid-phase microextraction

Solid-phase microextraction (SPME) is a relatively new technique in which a small, polymer-coated fiber is employed to extract volatile and semivolatile organic compounds from the sealed headspace above a questioned sample. SPME, coupled with gas chromatography/mass spectrometry (GC/MS), was used to characterize impurities in illicit methamphetamine samples. Trace impurities present in a specimen were tentatively identified using mass-spectral databases and included 1,2-dimethyl-3-phenyl-aziridine (indicating synthesis via a halogenated ephedrine intermediate), ethyl vanillin (a flavoring compound), and caffeine (a stimulant used as cutting agent). The types and numbers of organic compounds sampled by SPME were compared with those collected by various solvent extraction protocols. In addition to unambiguously confirming the presence of methamphetamine, SPME-GC/MS analyses detected approximately 30 more organic analytes than were found by GC/MS following the ethyl acetate extraction method adopted by the United Nations International Drug Control Programme. SPME-GC/MS is a superior method for generating material "fingerprint" profiles in methamphetamine samples. The detection and characterization of increased points of comparison in drug samples provide more detailed chemical signatures for both intelligence and operational information.     

Determination of impurities in illicit methamphetamine samples seized in Iran

In this study fifty samples of crystalline methamphetamine obtained from antinarcotics police of Iran seized during the year 2010 were analyzed. In order to determine the chemical characteristics of these samples, anion test, Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) were carried out on the samples. All of the samples containing methamphetamine tested positive for chloride anion. The range of methamphetamine hydrochloride content in these samples was 33-95%. One sample out of 50 contained no methamphetamine. The fact that 1,2-dimethyl-3-phenylaziridine was the most frequently found impurity in the analyzed samples, indicates that most of the methamphetamine samples seized in Iran have been synthesized from pseudoephedrine as starting material.     

The impurity characteristics of methamphetamine synthesized by Emde and Nagai method

Impurity profiling and classification of seized methamphetamine may play an important role in the interpretation of analytical results, the determination of the synthetic method employed, and the criminal investigations of drug traffic routes. Our study is focused on classifying seized methamphetamine samples according to the groups sorted by the types and quantities of impurities present in illicit methamphetamine samples. The samples (100 mg) were dissolved in 2 mL of potassium phosphate buffer (pH 7.0), extracted with 200 μL of ethyl acetate under basic condition, and then analyzed by gas chromatography-mass spectrometry (GC–MS) with a DB-1 capillary column (30 m × 0.25 mm i.d., 0.25 μm). Five impurities are used as criteria for the classification of seized methamphetamine samples by Emde and Nagai method. A total of fifty-two samples of seized methamphetamine were analyzed by GC–MS and classified by five organic impurities, and then sorted into four groups, which are Nagai type, Emde Type, Undetermined I type, and Undetermined II type.     

Australian Federal Police seizures of illicit crystalline methamphetamine ('ice') 1998-2002: impurity analysis

Nineteen crystalline methamphetamine ('ice') seizures captured by the Australian Federal Police (AFP) at the Australian border between 1998 and 2002 were analysed. Using a modified gas chromatograph-mass spectrometry (GC-MS) impurity profiling approach of these samples we have identified >30 compounds associated with methamphetamine and/or its synthetic route. Major impurities detected include 1,2-dimethyl-3-phenylaziridine 8, dimethylamphetamine 14, N-formylmethamphetamine 24, N-acetylmethamphetamine 25, 1,3-dimethyl-2-phenylnaphthalene 32, 1-benzyl-3-methylnaphthalene 33 and methamphetamine dimer 34. These data are suggestive of ephedrine/pseudoephedrine as the main precursor of the 'ice' samples seized during 1998-2002. Additionally the two naphthalenes 32 and 33 further identified that 15 items in 9 seizures were produced via the more specific ephedrine/hydriodic acid/red phosphorus method. One sample comprised 75% dimethylamphetamine and 9.7% methamphetamine, representing the first Australian seizure of imported dimethylamphetamine reported.     

Analysis of the impurities in the methamphetamine synthesized by three different methods from ephedrine and pseudoephedrine

Organic impurities of methamphetamine may show different patterns by synthesis. In the present study, we tried to find the impurities reflecting the conditions of synthesis by comparing impurity patterns of the methamphetamine samples synthesized by different methods. Sixteen methamphetamine samples were synthesized from ephedrine and pseudoephedrine by the three different manufacturing methods of Emde, Nagai and Moscow. The synthesized samples were extracted with ethyl acetate containing four internal standards, and the patterns of the organic impurities were investigated by GC-MS and GC-FID . Through the investigation, we found 10 peaks appearing in the latter part of GC chromatograms are characteristic to synthesis. The areas of the selected peaks were converted to the variables suitable for the statistical calculation, and the synthesized samples could be classified into four groups through the resultant cluster analysis.     

Methamphetamine impurity profiling using a 0.32 mm i.d. nonpolar capillary column

Classification of seized methamphetamine by impurity profiling can provide very useful information in criminal investigations of drug traffic routes, sources of supply and relationships between seizures. The aim of this study is to improve and develop an analytical method for detecting impurities such as starting materials and by-products in illegally prepared methamphetamine.HCl samples. A 50mg sample of methamphetamine.HCl was dissolved in 1 ml of buffer solution (four parts 0.1M phosphate buffer pH 7.0 and one part 10% Na2CO3). Impurities were extracted with 0.5 ml of ethyl acetate containing four internal standards (ISs) (n-decane, n-pentadecane, n-nonadecane and n-hexacosane) and analyzed by gas chromatography (GC) using a flame ionization detector (FID) on a DB-5 capillary column (0.32 mmi.d. x 30 m, film thickness 1.0 microm). The use of a middle-bore column offered better separation of the impurity peaks. The correction of the retention times of impurity peaks with four ISs made peak identification very accurate for subsequent data processing. Twenty-four characteristic peaks were selected for comparison and similarity and/or dissimilarity between samples, and the data were evaluated by the Euclidean distance of the relative peak areas after logarithmic transformation. The results indicate that the present method would be useful for methamphetamine impurity profiling.     

Contribution of thermal desorption and liquid-liquid extraction for identification and profiling of impurities in methamphetamine by gas chromatography-mass spectrometry

Impurity profiling of methamphetamine (MA) using thermal desorption (TD) and gas chromatography-mass spectrometry (GC-MS) was examined. Using TD/GC-MS, impurities were extracted and separated under various conditions. Optimal chromatograms were obtained when a 20 mg MA sample was extracted at 120 degrees C for 3 min using a TD instrument, followed by separation of the extracts using a non-polar capillary column coated with (5%phenyl)-methylpolysiloxane. MA samples from nine different batches were analyzed under optimized conditions. Compounds related to the structure of MA, such as benzaldehyde, benzyl alcohol, amphetamine, cis- and trans-1,2-dimethyl-3-phenylaziridine, dimethylamphetamine, and N-acetylephedrine, were detected in the chromatograms without any laborious extraction procedure. Compounds such as ethanol, diethyl ether, and acetic acid, which are considered reagents and solvents for MA synthesis, were also detected in some of the chromatograms. The numbers and intensities of the peaks detected were different among the samples. Impurity profiling of MA using TD was compared with that using liquid-liquid extraction (LLE). Better reproducibility of peak areas was obtained using LLE, whereas higher intensities and numbers of peaks were detected using TD. Solvents were extracted more effectively using TD. The nine batches of MA were classified using both extraction procedures. The nine batches were divided roughly into two groups using data from LLE. Subsequently, the groups were classified in detail using data from TD. TD can be used to provide supplemental information for LLE, and the combination of these extraction methods can be helpful for impurity profiling of MA.     

SPME/GC-MS characterization of volatiles associated with methamphetamine: toward the development of a pseudomethamphetamine training material

The headspace profiles of eleven methamphetamine (MA) samples have been analyzed using solid-phase microextraction/gas chromatography-mass spectrometry (SPME/GC-MS). Nine of the eleven are illicit MA seizures from the Southwest U.S. border. One sample is methamphetamine base synthesized in the Drug Enforcement Administration (DEA) Southwest Laboratory, and the remaining sample is pharmaceutical-grade methamphetamine hydrochloride that is used to make training aids for drug detecting canines. In addition. volatiles associated with 1-phenyl-2-propanone (P2P), a methamphetamine precursor, have been identified for comparison with those found in methamphetamine seizure and the two reference samples. Eighty-seven different compounds were identified from all the samples, not including simple hydrocarbons and aldehydes. Only seven occur consistently in all seizure samples, and these are: acetic acid, benzaldehyde, acetophenone, P2P, 1-phenyl-1,2-propanedione (P12P), 3-phenyl-3-buten-2-one, 1-chloro-1-phenyl-2-propanone. Dimethyl sulfone, a common cutting agent in methamphetamine. was found in six of the nine seizure materials. When the reference methamphetamine and P2P samples are included, only two compounds are common to all twelve samples, and these are benzaldehyde and P2P. As such, these two compounds are likely candidates for use in a pseudomethamphetamine (PM) formulation, and their effectiveness in eliciting a canine response is being evaluated before actual deployment.     

Effective injection in pulsed splitless mode for impurity profiling of methamphetamine crystal by GC or GC/MS

Gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) are commonly used for the impurity profiling of illegal drugs. For the impurity profiling of methamphetamine, it is very important to obtain information about impurities related to the manufacturing route and the precursor chemicals [B. Remberg, A.H. Stead, Drug characterization/impurity profiling, with special focus on methamphetamine: recent work of the United Nations International Drug Control Programme, Bull. Narcotics LI (1999) 97-117 ]. There are many artifact impurities arising from the preparation of samples and conditions of GC. Moreover, some impurities pose a barrier to the statistical processing of methamphetamine profiling. We investigated capillary GC analysis using pulsed splitless (PS/L) injection to minimize the thermal decomposition of impurities at the injection port and improve the transfer of samples into the column. We confirmed that the optimal conditions of PS/L-mode are 230 degrees C (injection temperature), 50 psi (pulsed pressure) and 1.1 min (pulsed time) for the methamphetamine profiling. Based on the impurity profiles of 48 methamphetamine crystals in PS/L-mode, we can achieve very easy handling and obtained, good results.     

Impurity profiling of methamphetamine hydrochloride drugs seized in the Philippines

Methamphetamine hydrochloride is one of the most widely used illicit drugs in the Philippines. In this study, we describe the application of cluster analysis of trace impurities in the profiling of the seized methamphetamine drug samples. Thirty milligrams of a homogenized drug sample were dissolved in 1 mL of pH 10.5 buffer solution and extracted with ethyl acetate containing three internal standards. The trace impurities were identified using gas chromatography-mass spectrometry (GC-MS) and quantified by gas chromatography with a flame ionization detector (GC-FID). Following previously reported methodologies, 30 impurity peaks were selected from the GC-FID chromatograms. The peak areas and retention times were referenced to the internal standards. The peak areas of the selected peaks were then grouped for cluster analysis. In order to check for consistency of clustering, two further cluster analyses were performed using 40 and 50 impurity peaks. Changes in clustering were observed in going from 30 to 40 impurity peaks, while analyses using 40 and 50 impurity peaks gave similar results. Thus, for the seized drug samples used in this study, cluster analysis using at least 40 impurity peaks showed better consistency of clustering as compared to analysis using 30 peaks only. Ten of the impurity peaks were identified, of which four were identified for the first time in methamphetamine drug samples. These are p-bromotoluene, N-benzyl amphetamine, N-ethyl amphetamine, and N-ethyl methamphetamine. The presence of phenyl-2-propanone (P2P), N,N-dimethyl amphetamine, and N-formyl amphetamine is indicative that these casework samples were synthesized using the Leuckart method.     

Population data on the 11 STR loci in the Upper Silesia (Poland)

Smuggling of methamphetamine is affected by enforced regulation and international situation, resulting in changes of precursors and synthetic methods used. Enantiomer ratio of methamphetamine can provide information concerning its precursor and synthetic method. This information is useful for the prevention of smuggling methamphetamine and its precursor, and resultant reduction of methamphetamine abuse. In the present study, we investigated on the enantiomer ratios of 433 crystalline methamphetamine samples seized in Korea from 1994 to 2005. Excluding 17 samples of low purity, 416 samples were used for enantiomer profiling. The methamphetamine samples were derivatized with (S)-(+)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride ((S)-(+)-MTPACl), and the derivatives were analyzed by GCMS in selected ion monitoring (SIM) mode. The enantiomer ratios of the samples were calculated from the standard calibration curves of each enantiomer, both of which showed good linearity in the range of 0-1.2 microg. Most of the seizures were pure S(+)-enantiomer, but 21% (95 of 416 samples) contained R(-)-enantiomer above 1%. They began to appear from 1997, and increased continuously up to 50% in the year 2005 (55 of 111 samples). From this study, we could find out that alternative precursors have been used recently for the illicit manufacture of methamphetamine seized in Korea.     

Raman Spectroscopy as a Simple,Rapid, Nondestructive Screening Test for Methamphetamine in Clandestine Laboratory Liquids

Raman spectroscopy has found increased use in the forensic controlled substances laboratory in recent years due to its rapid and nondestructive analysis capabilities. Here, Raman spectroscopy as a screening test for methamphetamine in clandestine laboratory liquid samples is discussed as a way to improve the efficiency of a laboratory by identifying the most probative samples for further workup among multiple samples submitted for analysis. Solutions of methamphetamine in ethanol, diethyl ether, and Coleman fuel were prepared in concentrations ranging from 0.5% to 10% w/v, and Raman spectra of each were collected. A concentration‐dependant Raman peak was observed at 1003 per cm in each solution in 4% w/v and greater solutions. Case samples were analyzed and also found to reliably contain this diagnostic peak when methamphetamine was present. The use of this diagnostic indicator can save the forensic controlled substances laboratory time and materials when analyzing clandestine laboratory liquid submissions.     

Identification of impurities and the statistical classification of methamphetamine using headspace solid phase microextraction and gas chromatography-mass spectrometry

The profiling of impurities in methamphetamine (MA) using headspace solid phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) is described. The extraction of the impurities with an SPME fiber was examined under varying conditions. Optimal chromatograms were obtained when a 50 mg MA sample at 85 degrees C for 30 min was extracted using a fiber coated with divinylbenzene/carboxen/polydimethylsiloxane. MA samples from nine different origins were analyzed under optimized extraction conditions. Compounds related to MA such as benzaldehyde, benzyl alcohol, amphetamine, benzyl methyl ketone, cis- and trans-1,2-dimethyl-3-phenylaziridine, dimethylamphetamine, N-acetylamphetamine, N-acetylmethamphetamine and N-formylmethamphetamine were detected in the chromatograms. Trace amounts of ethanol, diethyl ether and acetic acid were also detected in some of the chromatograms. The numbers and intensities of the peaks detected were different, depending on the sample. After the areas of the eight principal peaks were converted to their square root and logarithm, similarities among the samples were evaluated by Euclidian distance, cosine distance and correlation coefficient. The results showed that a combination of logarithmic conversion and cosine distance was the most suitable for discriminating and classifying the samples. HS-SPME/GC-MS is a simple and effective method for the extraction and identification of impurities. The present method, in combination with an appropriate statistical analysis, would be useful for developing a profile of impurities in MA.     

甲基苯丙胺对映异构体两种衍生化方法的比较分析

目的建立甲基苯丙胺毒品的对映异构体分析的优化方法。方法按文献方法用（S）-（＋）-a-甲氧基-a-（三氟甲基）苯基乙酰氯（MTPACl）对甲基苯丙胺直接衍生化和在碱性条件下用有机溶剂萃取后再用MTPACl衍生化（对文献方法优化）,分别对其衍生物采用全扫描形式进行GC-MS分析,比较其结果。结果优化方法的检测限低,峰型好,副反应少。文献方法的检测限是0.1ng,优化方法的检测限是0.001 6ng。结论优化方法用于甲基苯丙胺的对映体特征分析,结果更准确,实用性更强。     

Characteristics and trends of 3,4-methylenedioxymethamphetamine (MDMA) tablets found in Taiwan from 2002 to February 2005

One hundred and eighty-one 3,4-methylenedioxymethamphetamine (MDMA) containing tablets were sampled from confiscated drugs received by the Taiwan National Bureau of Controlled Drugs for testing from 2002 to February 2005. Sample tablets demonstrated various colors and logos. The appearances, contents of MDMA and other components in these tablets were analyzed in order to understand the characteristics and trends of MDMA use. Samples were analyzed using GC-MS methodology. Deuterated internal standards were used for drug quantification. The MDMA contents varied from 16 to 193 mg/tablet. 66-71% of the tablets seized each year contained only MDMA, and the content of MDMA in MDMA only tablets varied from 89 to 133 mg/tablet. There was a decreasing trend in MDMA content in these tablets over time. Other components commonly found besides MDMA included caffeine (18%), methamphetamine (7%), 3,4-methylenedioxyethylamphetamine (MDEA) (7%) and amphetamine (4%). 3,4-Methylenedioxyamphetamine (MDA), ketamine, ephedrine, diazepam, chlorzoxazone and nicotinamide were also detected. During the study period, the number of other drugs found as well as the combinations of different drugs detected in these tablets increased.     

甲基苯丙胺在家兔体内的毒物代谢动力学研究

目的研究甲基苯丙胺及其代谢物苯丙胺在家兔体内的毒物代谢动力学行为。方法GC/MS法测定家兔灌胃甲基苯丙胺后不同时间点血、尿中甲基苯丙胺和代谢物苯丙胺浓度,采用3P97程序进行房室模型拟合以及毒物代谢动力学参数计算。结果甲基苯丙胺和苯丙胺在家兔体内的毒物代谢动力学过程均呈一级动力学特征,符合二室开放模型。甲基苯丙胺在家兔体内Cm ax为1.457 mg/L±0.094 mg/L,Tm ax为1.557h±0.078h,t1/2 ka、t1/2α和t1/2β分别为0.384h±0.052h、1.614h±0.036h和3.007h±0.430h,CL为1.769 L/h/kg±0.114 L/h/kg。甲基苯丙胺的毒物代谢动力学方程为:C t=2.767 e-0.746 t+1.454 e-0.234 t+4.119 e-1.746 t。结论甲基苯丙胺在家兔体内吸收、消除和代谢都较快。建立的甲基苯丙胺毒物代谢动力学方程和参数可为甲基苯丙胺分析的合理取样、从血药浓度推断服毒时间以及甲基苯丙胺滥用的法医学鉴定提供理论依据。     

Abuse of smoking methamphetamine mixed with tobacco: I. Inhalation efficiency and pyrolysis products of methamphetamine

Experiments of smoking methamphetamine in tobacco have been investigated. Inhalation efficiencies of methamphetamine into tar were 6 to 17% according to the additive amounts, suction volume, and intervals of smoking. Major pyrolysis products of methamphetamine in tar were identified as methamphetamine, amphetamine, phenylacetone, dimethylamphetamine, N-formyl-, N-acetyl-, N-propionyl-, and N-cyanomethyl-methamphetamine by the spectral analysis of infrared spectra (IR), mass spectra (MS), and proton magnetic resonance spectra (PMR), and comparison with the samples synthesized from authentic samples by one step. The largest pyrolysis product was N-cyanomethylmethamphetamine which is a new compound and easily metabolized to methamphetamine in the body. Methamphetamine itself transferred into tar was not so large, but the total active compounds in tar which would be metabolized to methamphetamine in the body were considerably larger.     

超高效液相色谱法（UPLC）同时筛选检测吗啡等7种常见毒品

目的建立快速筛选检测中毒者血液、尿液中吗啡、甲基苯丙胺、苯丙胺、麻黄碱、3，4-亚甲基双氧甲基苯丙胺（MDMA）、3，4-亚甲基双氧苯丙胺（MDA）、氯胺酮并定量分析的方法；方法采用超高效液相色谱（UP—LC）-二极管阵列检测器（PAD）；结果峰面积和质量浓度的线性关系良好，分离效果好、速度快、灵敏度提高；结论该方法与传统的HPLC相比能够更好满足实际办案中吗啡、甲基苯丙胺、苯丙胺、麻黄碱、MDMA、MDA、氯胺酮等中毒者血液、尿液的筛选检测并定量分析。     

GC/MS检验不同案件中摇头丸

目的 分析不同案件缴获的“摇头丸”主要成分和添加物,为确定“摇头丸”的合成路线、非法来源提供依据.方法 以GC/MS检测法为主要检测方法.结果 检验的14个“摇头丸”主要成分为甲基苯丙胺和咖啡因,其中含有少量的其他杂质如麻黄碱和氯胺酮等.结论 检测的14个“摇头丸”样本其中12个含甲基苯丙胺,实为冰毒成分,1个为咖啡因均不属于摇头丸.     

Quantitative determination of amphetamines, cocaine, and opiates in human hair by gas chromatography/mass spectrometry

Hair of young subjects (N = 36) suspected for drug abuse was analysed for morphine, codeine, heroin, 6-acetylmorphine, cocaine, methadone, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA). The analysis of morphine, codeine, heroin, 6-acetylmorphine, cocaine, and methadone in hair included incubation in methanol, solid-phase extraction, derivatisation by the mixture of propionic acid anhydride and pyridine, and gas chromatography/mass spectrometry (GC/MS). For amphetamine, methamphetamine, MDA, MDMA, and MDEA analysis, hair samples were incubated in 1M sodium hydroxide, extracted with ethyl acetate, derivatised with heptafluorobutyric acid anhydride (HFBA), and assayed by GC/MS. The methods were reproducible (R.S.D. = 5.0-16.1%), accurate (85.1-100.6%), and sensitive (LoD = 0.05-0.30ng/mg). The applied methods confirmed consumption of heroin in 18 subjects based on positive 6-acetylmorphine. Among these 18 heroin consumers, methadone was found in four, MDMA in two, and cocaine in two subjects. Cocaine only was present in two, methadone only in two, methamphetamine only in two, and MDMA only in seven of the 36 subjects. In two out of nine coloured and bleached hair samples, no drug was found. Despite the small number of subjects, this study has been able to indicate the trend in drug abuse among young people in Croatia.