Liquid Chromatographic Properties and Aqueous Solution Stability of N-Hydroxy-3,4-methylenedioxyamphetamine

Abstract

The reversed-phase liquid chromatographic properties of N-hydroxy-3,4-methylenedioxyamphetamine (NOHMDA) were determined on a C8 stationary phase specifically prepared for the separation of basic compounds. NOHMDA and several N-alkyl MDA derivatives displayed excellent peak shape on this stationary phase without the need for competing bases such as triethylamine. The k' values for NOHMDA varied with mobile phase pH in the range of 2.5 to 6.0, but the retention of the primary amine, MDA, and N-alkyl MDAs remained relatively constant over this range. The pKa value for NOHMDA was determined by titration to be 6.22 compared to a pKa of 10.04 for MDA. Thus, the variation of k' with mobile phase pH for NOHMDA may be a result of appreciable changes in degree of protonation. The stability of NOHMDA was found to decrease with an increase in aqueous solution pH. At pH 7.0 the degradation half-life was determined to be 49.8 h, which decreased to 2.57 h at pH 10.0. Above pH 10.0 the decomposition to the corresponding oxime was too fast for a reliable half-life determination.

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

“…Especially, at pH 10, N-OH-MDMA was rapidly degraded with a half-life of less than 1 h. In contrast, N-OH-MDMA was stable at least for 24 h at pH 2. This pH-dependent stability is similar to that of N-OH-MDA reported previously [4].…”

“…The N-OH-MDA peak shape difference between the two columns was explained by the degree of unreacted silanol. This is supported by a previous report on addition of triethylamine, a silanol masking agent, improves the peak shape of N-OH-MDA [4].…”

“…To confirm whether N-OH-MDA was truly produced from N-OH-MDMA in alkaline solution, the ethyl acetate extract obtained from the alkaline solution of N-OH-MDMA oxalate was analyzed by GC-MS. GC-MS chromatograms obtained from this solution after storage showed increasing peak intensities for the overlapping peak of N-OH-MDA/MDP2P-oxime (the degradation product of N-OH-MDA in alkaline solution [4]) and MDMA-nitrone with timedependent decrease of the N-OH-MDMA peak intensity ( Fig. 4(a)).…”

“…From the instability of a similar drug, N-hydroxy-3,4-methylenedioxyamphetamine (N-OH-MDA, Fig. 1(b)), in neutral-to-basic aqueous solution [4], it is suspected that N-OH-MDMA is also unstable in aqueous solution. In addition, suitable liquidliquid extraction conditions to allow for analysis of this compound in biological samples have not been reported.…”

Identification of N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), an homologue derivative of "ecstasy"

“…And the toxicologist is called upon, therefore, to put to work the most powerful analytical techniques to separate by high performance liquid chromatography [8,[16][17][18][19][20][21][22][23][24][25][26][27]29,30], or gas chromatography [8,11,19,21,[23][24][25][26][27][29][30][31][32][33][34] and identify by mass spectrometry [8,11,19,21,[23][24][25][26][27][28][29][30][31][32][33][34], or nuclear magnetic resonance [17,19,32,35] these various "designer amphetamines". In this article, we shall pres...…”