The application of capillary electrophoresis for enantiomeric separation of N,N-dimethylamphetamine and its related analogs: intelligence study on N,N-dimethylamphetamine samples in crystalline and tablet forms.

This paper reports a new capillary zone electrophoresis method for the simultaneous chiral determination of the enantiomers of N,N-dimethylamphetamine (DMA), methamphetamine (MA), ephedrine (E), pseudoephedrine (PE) and methylephedrine (Me-E). In this study, a number of electophoretic parameters were examined and optimized including the choice of chiral selectors, the use of short-chain tetraalkylammonium cations, the effect of chiral selector concentration, buffer concentration, applied voltage and capillary temperature. Heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CD) and tetrabutylammonium (TBA) being the best chiral selector and buffer cation, respectively, the optimized electrophoretic conditions were found to be: 20 mM DM-beta-CD, 50 mM TBAPO(4) at pH 2.5, applied voltage at 30 kV and temperature at 25 degrees C. Under the optimized conditions, all analytes were well separated with resolution factors between 3.3 and 24.0 achieved. Using phentermine as an internal standard, the intra-day (n=8) precisions for the relative migration times and peak areas of all analytes were below 1.09%, while the inter-day precisions (n=12, 6 days) for the relative migration times and peak areas of all analytes were under 3.77%. This method has been applied to the measurement of the enantiomeric purities of the seized DMA samples. The result of the measurement could provide important clues about the possible synthetic pathways of these samples.

Impurity profiling of ecstasy tablets seized in Hong Kong by gas chromatography-mass spectrometry.

In Hong Kong, ecstasy tablets are more commonly known as "Fing Tau Yuen", literally meaning "Shake Head Pills". The tablets contain mainly amphetamine-type stimulants (ATS) including 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), methamphetamine (MA) and/or ketamine. Adulterant such as caffeine was also detected in the tablets. This paper reports a study on the impurity profiles of ecstasy tablets from 89 seizures in Hong Kong from 2002 to early 2004. Tablet samples were extracted by diethyl ether under alkaline condition and then analyzed by gas GC-MS. The chromatograms obtained were compared. A total of 19 identified impurities were selected as markers for impurity profiling. They are different precursors, intermediates and by-products. The data matrices were examined by hierarchical cluster analysis (HCA), and then the ecstasy tablets were classified into different groups. Cluster analysis of ecstasy tablets is shown to be capable of providing intelligence on clandestine laboratory networks.

Chemical profiling of 3,4-methylenedioxymethamphetamine (MDMA) tablets seized in Hong Kong.

During 2000-2001, the Government Laboratory of Hong Kong received over 600,000 ecstasy tablets in more than 2,600 cases. Using GC-MS or FTIR, the major amphetamine-type stimulants were identified, and the samples were categorized into four groups containing: (1) 3,4-methylenedioxymethamphetamine (MDMA), (2) methamphetamine (MA), (3) 3,4-methylenedioxyamphetamine (MDA), or (4) amphetamine. Our study revealed that in Hong Kong MDMA tablets have made up 98 and 71% of the total ecstasy tablets examined in 2000 and 2001, respectively. Among the MDMA cases, 613 cases involving a total of 123,776 tablets in 2001 were randomly selected, and their active ingredients, minor ingredients, and/or impurities were studied using GC-MS and HPLC. Based on the chemical profiles, and irrespective of their different physical characteristics, tablets obtained in different seizures could be determined as to whether or not they could have come from a common origin. The impurities detected in the MDMA tablets also served as excellent chemical markers from which plausible synthetic route(s) of the MDMA were inferred. Our study revealed that 3,4-methylenedioxyphenyl-2-propanone (MDP2P), 3,4-methylenedioxyphenyl-2-propanol (MDP), 3,4-methylenedioxy-N-methylbenzylamine (MDB), piperonal and N-formyl-3,4-methylenedioxymethamphetamine (N-formyl-MDMA) were the most common impurities detected in MDMA tablets seized in Hong Kong. The finding of the phosphate salt of MDMA is intriguing. Based on a presumptive color test, spectroscopic data (FTIR/ESI-MS) and the percentage of MDMA content in a purified phosphate salt of MDMA, the ratio of the phosphate to MDMA was determined to be 1:1, suggesting that the compound is a dihydrogen phosphate salt [i.e. (HMDMA)H2PO4].

Enantiomeric separation of methamphetamine and related analogs by capillary zone electrophoresis: intelligence study in routine methamphetamine seizures.

A method for simultaneous enantiomeric separation of ephedrine, pseudoephedrine, and methamphetamine (MA) in a single run by simple capillary zone electrophoresis (CZE) with beta-cyclodextrin as a chiral selector is described. The effects of the buffer pH, phosphate concentration, beta-cyclodextrin concentration, voltage and temperature on the peak resolution were examined. Good enantiomeric resolution was attained for each analyte under our optimized conditions: 15 mM beta-cyclodextrin, 300 mM NaH2PO4 at pH 2.5 with an uncoated capillary (64.5 cm x 50 microm), applied potential at 20 kV and temperature at 30 degrees C. Ultraviolet (UV) detection at a fixed wavelength (200 nm) was employed using a diode array detector. Using phentermine as an internal standard, migration times for all analytes are reproducible within 0.16% for intra-day and 0.6% for inter-day runs. Application of this method to the analysis of confiscated drugs is discussed.