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.
The metabolism and urinary excretion of N hydroxy 3,4 methylenedioxymethamphetamine (N OH MDMA), a newly banned narcotic in Japan, were explored to conˆrm biotransformation of N OH MDMA to 3,4 methylenedioxymethamphetamine (MDMA) and to discriminate between N OH MDMA and MDMA intake in forensic urine analysis. The in vitro and the in vivo experiences were performed with human liver S9 and rats, respectively, and the resultant products or metabolites were determined using liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry.In both the in vitro and the in vivo experiences, MDMA and 3,4 methylenedioxyamphetamine (MDA) were detected, and the MDA levels exceeded the MDMA levels throughout the entire periods except for during 3 h after administration to the rats. This suggests the existence of the metabolic pathway(s) from N OH MDMA to MDA not via MDMA. In urine samples from the administered rats parent N OH MDMA and its demethylated metabolite N hydroxy 3,4 methylenedioxyamphetamine (N OH MDA) with very low levels during short period after administration (6 h) were detected. The ratios of the urinary MDA/ MDMA levels for N OH MDMA administered rats were higher than those for MDMA administered rats. In addition, the determination of urinary diastereomers of glucuronidated 4 hydroxy 3 methoxymethamphetamine (HMMA), MDMA metabolite, revealed that the relative peak intensity of l HMMA glucuronide to d
The urinary concentrations of the main metabolites of methamphetamine (MA), speciˆcally p hydroxymethamphetamine-sulfate (p OHMA-Sul) and p hydroxymethamphetamine-glucuronide (p OHMA-Gul) have been directly measured in MA users using an optimized LC ESI MS method.The concentrations of the main metabolites and unchanged MA in 50 MA users' urine ranged from 0.02 to 21.7 mg/ml for p OHMA Sul, from <0.02 to 2.43 mg/ml for p OHMA Glu, from <0.005 to 1.33 mg/ml for p hydroxymethamphetamine (p OHMA), from 0.01 to 6.79 mg/ml for amphetamine (AP) and from 0.04 to 133 mg/ml for MA, and the ratios of sulfate to glucuronide (S/G ratios) ranged from 2.2 to 37.1 (13.8±8.1). These results demonstrate that the majority of p OHMA is eliminated as its conjugate and the sulfation is quantitatively more important than glucuronidation for the conjugation of p OHMA in humans. The urinary concentration time-dependency in two MA users have also revealed that the conjugates were mostly excreted in urine within 3 days post-intake.Both the acid and enzymatic hydrolysis conditions for p OHMA conjugates were also optimized using the authentic standards of p OHMA Sul and p OHMA Gul. In the acid hydrolysis, the hydrolysis rate of p OHMA Sul was faster than p OHMA Glu, and a 3 h incubation with 1.2 mol/l HCl at 98 degrees Celsius gave complete hydrolysis of p OHMA Sul and p OHMA Glu. On the other hand, the enzymatic hydrolysis of two conjugates with Sulfatase Type H 1 from Helix pomatia required 6 hours for completion.
In this study, we describe a rapid gas chromatography-tandem mass spectrometry (GC MS/MS) analytical method that allows comprehensive detection and structural elucidation of synthetic cathinone-type designer drugs. Our proposed method consists of three simultaneous analytical procedures: 1) selective detection of the carbonyl group characteristic to each cathinone examined via selected reaction monitoring (SRM); and the determination of both 2) iminium cations and 3) substituted benzoyl cations generated via the a cleavage of their corresponding amines and ketone moieties via product ion scanning, respectively.One peak was detected in the SRM chromatogram for all cathinones examined in procedure 1), as well as the relevant single peaks in the total ion current chro-
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