Degradation of N-hydroxy-3,4-methylenedioxymethamphetamine in aqueous solution and its prevention

N-Hydroxy-3,4-methylenedioxymethamphetamine (N-OH-MDMA) is a lesser known psychedelic drug that has recently circulated in the Japanese illicit drug market. From the instability of the similarly structured N-hydroxy-3,4-methylenedioxyamphetamine (N-OH-MDA) in neutral-to-basic aqueous solution, it was presumed that N-OH-MDMA would also degrade in aqueous solution. The aims of this study were: (i) investigation of the degradation of N-OH-MDMA in aqueous solution and its prevention, (ii) identification of the degradation products, (iii) determination of the pKa for the conjugate acid of N-OH-MDMA, and (iv) evaluation of liquid–liquid extraction recovery. N-OH-MDA was also included in some of these studies.N-OH-MDMA degraded to 14.9% of initial concentration after 2 h storage in pH 10 buffer solution at 22 °C. This degradation was completely inhibited at least for 2 h by addition of l-ascorbic acid, a strong reactive oxygen scavenger. These findings indicate that reactive oxygen species in alkaline solution were involved in N-OH-MDMA degradation. N-OH-MDA, α-methyl-(N-methylene)-3′,4′-methylenedioxybenzeneethanamine and 3′,4′-methylenedioxyphenyl-2-propanone oxime were found as degradation products of N-OH-MDMA in alkaline solution. The pKa for the conjugate acid of N-OH-MDMA was determined by titration to be 5.52, which was much lower than that reported for 3,4-methylenedioxymethamphetamine (pKa = 10.38). Excellent recoveries for N-OH-MDMA and N-OH-MDA (>98%) were achieved by extraction with ethyl acetate or chloroform from a basic buffer (pH 10) solution containing 0.1% l-ascorbic acid.