Analyses of a methamphetamine precursor <i>N-tert</i>-butoxycarbonyl-methamphetamine (<i>t</i>-BOCMA) and its behavior in simulated human gastric juice

Abstract

N-tert-Butoxycarbonyl-methamphetamine (t-BOCMA), a tert-butoxycarbonyl (t-BOC) derivative of methamphetamine (MA), which has recently been reported in several countries, was seized for theˆrst time in Japan in 2017. It deprotected easily in an acidic condition to result in an illicit MA, and recently became a newly designated drug of the Pharmaceutical and Medical Device Act. For drug enforcement, the information of its properties was, therefore, strongly demanded. In this study, we synthesized the t-BOCMA standard, acquired various analytical data, and demonstrated its conversion to MA in high yield in the relatively moderate acidic condition (5 HCl methanol solution, 50°C). Also, the stability of t-BOCMA in simulated gastric juice (0.08 M HCl, 37°C) was explored by using GC/MS. As the result, 19 of t-BOCMA remained even after 120 min incubation, and the T 1/2 was calculated to be 50 min. These suggest that the orally ingested t-BOCMA would be absorbed into blood in some degree without conversion to MA.

Human and rat microsomal metabolites of N-tert-butoxycarbonylmethamphetamine and its urinary metabolites in rat

“…These results suggested the intravenously injected and inhaled BocMA do not lead to the production of MA and its metabolites in biological samples. It seems only oral intake causes BocMA to convert into MA in gastric juice [7]. Our previous report suggested the gradual degradation (half-life: 50 min in gastric juice model) will allow BocMA to undergo absorption followed by metabolism and excretion, and produce metabolites for proving its intake.…”

“…The authentic standards including BocMA, six metabolite candidates M1-D1, M1-D2, M2, M3, M4, Boc-protected methcathinone (BocMC) and internal standard (IS, N-valerylmethamphetamine) were chemically synthesized as shown in procedures ( 1)- (7). All standards were purified with silica gel column chromatography followed by identification using nuclear magnetic resonance spectroscopy (NMR).…”

“…In our previous study, we evaluated the stability of BocMA in model gastric juice solution (pH 1.5, 37 °C), and showed its gradual decomposition with a half-life of 50 min [7]. This result indicated that some portion of the orally ingested BocMA can pass through the stomach into the intestine without converting into MA, and undergo absorption followed by first-pass effect in the liver.…”

“…The Boc group has been commonly used for protecting primary and secondary amines in organic synthesis. Boc protection is generally stable against heat, bases, and oxidation, whereas they can be easily de-protected by treatment with strong acids to produce the desired compound in excellent yield [4][5][6][7]. Kurakami et al reported that BocMA converted quickly into MA in heated hydrogen chloride aqueous solution (HClaq) at good yield [6].…”

“…BocMA is of increasing concern, acting as new smuggling operation tools due to the masked chemical structure that circumvents legal restrictions. In addition, previous studies showed that BocMA yields MA by exposure to simulated gastric juice including diluted HClaq at 37 °C (body temperature), making it an excellent potential precursor drug following oral administration [7]. Collins et al reported that N-tert-butoxycarbonylmethylenedioxymethamphetamine (BocMDMA) seized in Australia showed the same potential of being a precursor drug for MDMA [8].…”