Separation and identification of stereoisomers of methamphetamine and impurities of its illicit synthesis: 1,2-dimethyl-3-phenyl aziridine and chloroephedrine

Separation and identification of methamphetamine stereoisomers is helpful to forensic toxicologist in distinguishing legal from illegal drug use. Additionally, such analysis may enable forensic toxicologist to identify the route of illicit methamphetamine synthesis; and thereby alert law enforcement agencies to the need to regulate the availability of specific precursor chemical(s) used in the synthesis. Chiral analysis is also useful in pharmacokinetic studies of drugs such as selegiline and benzphetamine which are metabolized to methamphetamine.; Initially, an enantiomeric separation of amphetamine and methamphetamine in urine by chiral high-pressure liquid chromatography (HPLC) using Chirex chiral stationary phase 3022; (S)-indole carboxylic acid and (R)-1-napthylethylamine (Phenomenex, CA), was developed. Quantitative analysis was performed with the method of peak height ratios. Calibration curves were linear from 50--5,000 ng/ml with a LOD of 20 ng/ml. Popular phenylisopropyl amine drugs were found not to interfere with the method. The results of enantiomeric analysis of 30 urine specimens from methamphetamine abusers by the presented method and chiral gas chromatography/Mass spectrometry (GC/MS) were compared by linear regression analysis which yielded good correlation for each enantiomer: r 2s range from 0.952 to 0.974. Results of the HPLC analysis of urines collected from substance abuse treatment center clients revealed that d-methamphetamine was the predominate isomer found. These data indicated that methamphetamine was illicitly manufactured from a chiral synthetic route. In order to determine if reduction of ephedrine or pseudoephedrine by thionyl chloride was the synthetic method, it was necessary to develop an analytical procedure for the identification of synthetic byproducts such as cis-1,2-dimethyl-3-phenyl aziridine and chloroephedrine. Stability studies showed that cis-aziridine was unstable in acidic and basic buffers. The decomposition products of cis-aziridine were not completely characterized. Attempts to simultaneously determine methamphetamine and cis-aziridine in samples by acid anhydride derivatization followed by GC/MS analysis resulted in the detection of methamphetamine and pseudoephedrine. In acidic solutions (pH ≤ 5.0) containing 0.5 M NaCl, cis-aziridine is converted to chloroephedrine. chloroephedrine.HCl when analyzed by GC/MS was detected as cis-aziridine. In attempts to follow this conversion, it was found that at high GC/MS injector port temperatures, chloroephedrines were converted not only to aziridines but also to other rearrangement products. Although the toxicity of aziridine and chloroephedrine is unclear, aziridine is expected to be more toxic than chloroephedrine. Smoking methamphetamine may cause the thermal conversion of chloroephedrine to aziridine, which, in turn, may increase the toxicity of illicit methamphetamine.