Contaminants in illegal amphetamine. Basic contaminants in drug market 3,4-(methylenedioxy)methylamphetamine]

In this paper a survey is given concerning the production of illegal MDMA preparations. It was found that the reductive amination and the Leuckart syntheses were used for this purposes.     

Contamination in illegal amphetamine. Contaminants resulting from the synthesis of 3,4-(methylenedioxy)amphetamine (MDA) via condensation between nitroethane and piperonal]

Some impurities of illegally synthesized 3.4-(methylenedioxy)amphetamine (MDA) are presented. These compounds were detected in laboratory glassware which had been used for the synthesis of MDA via phenyl nitropropene route.     

3,4-Methylenedioxymethamphetamine (MDMA) and other amphetamine derivatives

As various substances of abuse come under Drug Enforcement Administration (DEA) Schedule restrictions, slightly modified derivatives (designer drugs) replace them. A series of amphetamine derivatives are discussed in this presentation. Applicable analytical methods are presented. Details of cases handled by the office (hospital patients, driving while under the influence/driving under the influence of drugs [DWI/DUID], and medical examiner cases) are discussed.     

A review of impurity profiling and synthetic route of manufacture of methylamphetamine, 3,4-methylenedioxymethylamphetamine,amphetamine, dimethylamphetamine and p-methoxyamphetamine

Amphetamine-type substances (ATS), like other synthetically derived compounds, can be produced by a multitude of synthetic pathways using a variety of precursors and reagents, resulting in a large number of possible contaminants (by-products, intermediates and impurities). This review article describes the common contaminants found in preparations of methylamphetamine (MA), 3,4-methylenedioxymethylamphetamine (MDMA), amphetamine (AP), N,N-dimethylamphetamine (DMA) and p-methoxyamphetamine (PMA) synthesised via common synthetic pathways including reductive amination, Leuckart method, Nagai method, Emde method, Birch reduction, “Moscow” method, Wacker process, “Nitrostyrene” method and the Peracid oxidation method.Contaminants can facilitate identification of the synthetic route, origin of precursors and may suggest information as to the location of manufacture of these illicit drugs. Contaminant profiling can provide vital intelligence for investigations in which linking seizures or identifying the synthetic pathway is essential. This review article presents an accessible resource; a compilation of contaminants resulting from a variety of manufacturing methods used to synthesise the most common ATS. It is important for research in this field to continue as valuable information can be extracted from illicit drug samples, increasing discrimination amongst ATS, and in turn, leading to an increase in evidential value and forensic drug intelligence from forensic drug samples.     

Distribution of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) stereoisomers in a fatal poisoning

This communication presents the quantitation and differential distribution of the enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and its physiologically active metabolite 3,4-methylenedioxyamphetamine (MDA) in a fatal poisoning following insufflation of MDMA, cocaine and heroin. Animal studies have demonstrated the stereoselective pharmacokinetics and neurotoxicity of these compounds; however, enantiomeric distributions have not been reported in humans. Quantitation of MDMA and MDA enantiomer was by gas chromatography/mass spectrometry (GC/MS) following chiral derivatization with N-trifluoroacetyl-l-triproyl chloride (LTPC). The decedents' blood concentration of S(+)-MDMA was slightly less than that of R(−)-MDMA (1.3 vs. 1.6 mg/l, respectively), while the S(+)- and R(−)-MDA blood concentrations were identical (0.8 mg/l). Both primary routes of excretion, bile and urine, had greater concentrations of R(−)-MDMA than the S(+) isomer. These fluids also contained twice the concentration of S(+)-MDA than the R(−)-isomer. These data indicate that S(+)-MDMA is metabolized and eliminated faster than R(−)-MDMA. The results appear to support the findings in animals regarding stereoselective metabolism of MDMA.     

The Characterization of 3,4-Dimethylmethcathinone (3,4-DMMC)

Analogs and derivatives of traditional illicit drugs are ever increasing in variety and creativity. Staying abreast of the new developments is a constant challenge for every forensic laboratory. Recently, a seizure from Australian Customs Service presented our laboratory with the designer cathinone 3,4-dimethylmethcathinone (3,4-DMMC). Gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS), nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, and ultraviolet (UV) spectrophotometry were employed to analyze the spectroscopic characteristics of this cathinone. As an analog, 3,4-DMMC exhibits similar if not identical IR and UV profiles to mephedrone (4-MMC) and methcathinone; however, the retention time from GC is unique as expected, and the electron impact fragmentation pattern is consistent with the fragmentation pattern of other cathinones. The chemical shifts of the carbons and hydrogens were assigned by both one- and two-dimensional NMR techniques, while the molecular weight was confirmed by LC/MS.     

Methyl 3-[3',4'-(methylenedioxy)phenyl]-2-methyl glycidate: an ecstasy precursor seized in Sydney, Australia

Five 44 gallon drums labeled as glycidyl methacrylate were seized by the Australian Customs Service and the Australian Federal Police at Port Botany, Sydney, Australia, in December 2004. Each drum contained a white, semisolid substance that was initially suspected to be 3,4-methylenedioxymethylamphetamine (MDMA). Gas chromatography-mass spectroscopy (GC/MS) analysis demonstrated that the material was neither glycidyl methacrylate nor MDMA. Because intelligence sources employed by federal agents indicated that this material was in some way connected to MDMA production, suspicion fell on the various MDMA precursor chemicals. Using a number of techniques including proton nuclear magnetic resonance spectroscopy ((1)H NMR), carbon nuclear magnetic resonance spectroscopy ((13)C NMR), GC/MS, infrared spectroscopy, and total synthesis, the unknown substance was eventually identified as methyl 3-[3',4'(methylenedioxy)phenyl]-2-methyl glycidate. The substance was also subjected to a published hydrolysis and decarboxylation procedure and gave a high yield of the MDMA precursor chemical, 3,4-methylenedioxyphenyl-2-propanone, thereby establishing this material as a "precursor to a precursor."     

Analysis of dyes in illicit pills (amphetamine and derivatives)

The determination of dyes present in illicit pills is shown to be useful and easy-to-get information in strategic and tactical drug intelligence. An analytical strategy including solid-phase extraction (SPE) thin-layer chromatography (TLC) and capillary zone electrophoresis equipped with a diode array detector (CZE-DAD) was developed to identify and quantify 14 hydrosoluble, acidic, synthetic food dyes allowed in the European Community. Indeed, these may be the most susceptible dyes to be found in illicit pills through their availability and easiness of use. The results show (1) that this analytical method is well adapted to small samples such as illicit pills, (2) that most dyes actually found belong to hydrosoluble, acidic, synthetic food dyes allowed in the European Community, and (3) that this evidence turns out to be important in drug intelligence and may be assessed into a Bayesian framework.     

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) and driving impairment.

3,4-Methylenedioxymethamphetamine, or MDMA, is increasing in popularity in the United States as a drug of abuse. It has stimulant and empathogenic mood altering properties with the potential to affect psychomotor skills and impact driving. This report reviews the literature relating to the relevant psychomotor effects of the drug, the relationship between dose and blood concentrations, and studies and case reports on specific effects of the drug on driving. The latter reports include both laboratory driving simulator studies and anecdotal reports, and case series. We also report details of eighteen cases of apparent MDMA impaired driving, including six drivers whose blood tested positive for MDMA alone. Most subjects displayed muscle twitching and body tremors, dilated pupils, slow pupillary reaction to light, elevated pulse and blood pressure, lack of balance and coordination, and most were perspiring profusely. Five of the six subjects were given field sobriety tests (one leg stand, walk and turn test), and all five performed poorly. There was no clear correlation between the blood concentration of MDMA and the specific demeanor of the subject. These findings are consistent with other reports, and lead to the conclusion that MDMA use is not consistent with safe driving, and that impairment of various types may persist for a considerable time after last use.     

Determination of synthesis route of 1-(3,4-methylenedioxyphenyl)-2-propanone (MDP-2-P) based on impurity profiles of MDMA

In our study 1-(3,4-methylenedioxyphenyl)-2-propanone (MDP-2-P or PMK) was prepared by two different routes, i.e. by oxidizing isosafrole in an acid medium and by 1-(3,4-methylenedioxyphenyl)-2-nitropropene reduction. The final product-MDP-2-P was subjected to GC/MS analysis. The intermediates and reaction by-products were identified and the 'route specific' impurities were established. The following impurities are the markers of the greatest importance: 1-(3,4-methylenedioxyphenyl)-1-propanone (compound 10, Table 2), 1-methoxy-1-(3,4-methylenedioxyphenyl)-2-propanone (compound 11, Table 2) and 2,2,4-trimethyl-5-(3,4-methylenedioxyphenyl)-[1,3]dioxolane (compound 13, Table 2) (the 'oxidising isosafrole route') and N-cyclohexylacetamide (compound 3, Table 1), 3-methyl-6,7-methylenedioxyisoquinoline-1,4-dione (compound 15, Table 1) (the 'MDP-2-nitropropene reduction route'). Subsequently, MDMA was prepared by reductive amination of MDP-2-P using NaBH4 as reducing agent (so-called 'cool method'). Impurities were extracted with n-heptane under alkaline conditions. The impurity profiles were obtained by means of GC/MS, some reaction by-products were identified by means of the EI mass spectra including low energy EI mass spectra and 'route specific' impurities were established. 4-Methyl-5-(3,4-methylenedioxyphenyl)-[1,3]dioxolan-2-one (compound 22, Table 2), N-methyl-2-methoxy-1-methyl-2-(3,4-methylenedioxyphenyl)-ethaneamine (compound 18, Table 2), 3-methyl-6,7-methylenedioxyisoquinoline-1,4-dione (compound 15, Table 1) and N-cyclohexyloacetamide (compound 3, Table 1) were found to be the synthesis markers of greatest importance.     

Evaluation of 5-(4-nitrophenyl)-2,4-pentadien-1-al (NPPD) as a tracer for shadowing pursuits

The chemical compound 5-(4-nitrophenyl)-2,4-pentadien-1-al (NPPD), called "spy dust," was used in the Soviet Union as a shadowing pursuit, the act of following someone secretly, for investigating the activities of diplomatic personnel. It is also useful for counter-terrorism, and some criminal cases in the forensic science field. In this paper, it was synthesized and evaluated as a tracer for shadowing pursuits. The method for utilizing this reagent was very simple: it was dissolved in methanol (1 mg/mL) and sprayed on the restricted area. If the suspect was to enter this area or touched the sprayed material, NPPD was attached to the suspect's shoe surface or hands. The color examination was a two-steps process: first was the addition of 1 mL of a 0.1% naphthoresorcinol methanol solution to the methanol extracts of a methanol-contained cotton swab used to smear some surfaces of the suspect, and second, the addition of 1 mL of concentrated hydrochloric acid, which turned the solution dark red. The gamma max of the colored solution was 510 nm, measured by ultraviolet-vis spectroscopy. Detection limits for three methods were determined: a visual method (detection limit 100 ng/3 mL), an ultraviolet-visible spectrometric method (detection limit 10 ng/3 mL), and a selected-ion-monitoring gas chromatographic/mass spectrometric method (detection limit 300 pg/injection). The forensic utility of NPPD was demonstrated for two simulated cases: a theft case and a case where NPPD was used as a tracer to prove that an automobile had entered a restricted area. These examinations prove NPPD is a useful shadowing pursuit (spy dust) for the forensic science field.     

Organic impurity profiling of 3,4-methylenedioxymethamphetamine (MDMA) tablets seized in The Netherlands.

In this study, a new method was developed for the impurity profiling of illicit MDMA tablets. The extraction efficiency, linearity, repeatability and reproducibility of the method were evaluated. Eighty two MDMA tablets coming from presumed unrelated large seizures in 2004 (n >500 tablets) were analyzed by gas chromatography mass spectrometry (GC-MS) in order to assess the discrimination power of the method. The latter was found to be practical, robust, relatively easy to perform, highly discriminative and yielding good chromatography. In addition, some new impurities were detected and identified. Their chemical structures and mass spectra are reported.     

5-(4-Nitrophenyl)-2,4-pentadien-1-al (NPPD) used as a tracer by nonscientists at a simulated crime scene

5-(4-Nitrophenyl)-2,4-pentadien-1-al (NPPD) was used as a tracer by nonscientists at a simulated crime scene. A card with both a plastic-coated smooth surface and a porous cellulose matrix paper surface was coated with a methanol solution containing 0.5mg/mL of NPPD. The card was touched with bare fingers and fingers covered by a cotton glove. A color-change protocol was then used to detect the presence of NPPD. The bare fingers or the fingers of gloves were swabbed with a cotton swab, or the parts of the glove that had touched the card were cut out. The swabs or the cloth pieces were dipped in methanol, a 0.1% methanol solution of naphthoresorcinol was added, and then concentrated hydrochloric acid was added. The observation of a red color at this point indicated a positive test. NPPD was easily observed in the experiments involving bare fingers, but no color change was observed from the swabbing of the cotton glove. However, when the cloth pieces cut from the fingers of the glove were subjected to the test, the red color was observed. In an attempt to enhance the sensitivity of the test, the volumes of the reagent solutions were reduced, but no improvement in sensitivity was obtained.     

“国策会社”日清公司论析（1907-1939）

日清公司(日清汽船株式会社)是二战前日本在华航运企业的重要代表.在其32年的企业经营中,一直受到日本政府的"补助金"资助,是日本航运界担负着其政府"国策使命"的"国策会社".通过对日清公司的兴办及运营状况及其对长江流域社会经济产生深刻影响的考察和分析,可以揭示其侵略本质,反映日本战前对华航运业的投资不单纯是一种经济行为,而是日本对华侵略的重要决策之一.因此,日清公司实质上就是日本对华经济侵略的一个重要工具.     

Impurities in illicit amphetamine. 7. Identification of benzyl methyl ketone phenylisopropylimine and benzyl methyl ketone benzylimine in amphetamine

The identification of the Schiff bases benzyl methyl ketone phenylisopropylimine and benzyl methyl ketone benzylimine by both high- and low-resolution mass spectrometry is reported. Both substances are found in amphetamine produced illegally by a reductive amination of benzyl methyl ketone.     

应用一滴溶剂萃取（SDE）技术提取尿样中苯丙胺类毒品

目的建立一滴溶剂萃取技术（SDE）在尿样中苯丙胺类毒品检验的提取优化方法。方法通过GC／NPD分析，系统考察了溶剂体积，萃取溶剂，搅拌速度，萃取时间等参数对苯丙胺类毒品的SDE萃取效率的影响。结果经实验研究，建立了SDE最优化方法。结论SDE技术是一种新型样品前处理技术，具有操作简单快速，成本低廉等特点，在毒物毒品检验中具有广泛的应用前景。     

Reidentification of a major impurity in illicit amphetamine

An impurity previously reported in illicit amphetamine has been found as a by-product om the synthesis of N-formylamphetamine, a reaction precursor to amphetamine by the Leukart synthesis. Its reidentification as di-(1-phenylisopropyl) formamide has been supported by combined spectroscopic analysis of isolated fractions.     

Identification of 1-butyl-3-(1-(4-methyl)naphthoyl)indole in a herbal mixture

Besides the cannabinoid mimetic JWH-073, a novel 4 methylnaphthoyl homologue of JWH-073 was detected in a herbal mixture. The structure of the compound was elucidated after thin layer chromatographic enrichment from the herbal mixture by nuclear magnetic resonance (NMR) and gas chromatographic mass spectrometric (GC-MS) analysis. The paper outlines data after GC-MS, liquid chromatography mass spectrometry (LC-MS) and NMR spectroscopy, and describes the structure elucidation.