Investigation of the reaction impurities associated with methylamphetamine synthesized using the Nagai method.
The synthesis of methylamphetamine hydrochloride from l-ephedrine or d-pseudoephedrine hydrochloride via reduction with hydriodic acid and red phosphorus was investigated. Eighteen batches of methylamphetamine hydrochloride were synthesized in six replicate batches using three different reaction times. This allowed the investigation of the variation of impurities in the final product with reaction time. The results obtained have resolved previously conflicting impurity profile data reported in the literature for this synthesis route. The impurity profile was shown to change with reaction time, and all previously reported impurity components were identified but not in all batches. Additionally, 20 batches of methylamphetamine hydrochloride were synthesized from either from l-ephedrine or d-pseudoephedrine hydrochloride in reactions which were allowed to proceed for 24 h. The impurities present in the resulting batches were investigated, and route-specific impurities present in all batches were identified. Batch-to-batch fluctuations in the resultant chromatographic impurity profile, despite careful synthetic monitoring and control, were also noted.
Centre for Forensic Science, Department of Pure and Applied Chemistry, WestCHEM, University of Strathclyde, Glasgow, Scotland, UK.
Vanitha
V
Kunalan
William J
WJ
Kerr
Niamh Nic
NN
Daéid
D000143:Acids / Q000138:chemical synthesis / Q000737:chemistry*; D000697:Central Nervous System Stimulants / Q000138:chemical synthesis* / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D004340:Drug Contamination; D004809:Ephedrine / Q000138:chemical synthesis / Q000737:chemistry*; D017613:Iodine Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D008694:Methamphetamine / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction
D000143:Acids; D000697:Central Nervous System Stimulants; D017613:Iodine Compounds; D008694:Methamphetamine; C010466:hydroiodic acid; D004809:Ephedrine