Phase I and II metabolites of speciogynine, a diastereomer of the main Kratom alkaloid mitragynine, identified in rat and human urine by liquid chromatography coupled to low- and high-resolution linear ion trap mass spectrometry

J Mass Spectrom. 2010 Nov;45(11):1344-57. doi: 10.1002/jms.1848. Epub 2010 Oct 21.

Abstract

Mitragyna speciosa (Kratom in Thai), a Thai medical plant, is misused as herbal drug of abuse. Besides the most abundant alkaloids mitragynine (MG) and paynantheine (PAY), several other alkaloids were isolated from Kratom leaves, among them the third abundant alkaloid is speciogynine (SG), a diastereomer of MG. The aim of this present study was to identify the phase I and II metabolites of SG in rat urine after the administration of a rather high dose of the pure alkaloid and then to confirm these findings using human urine samples after Kratom use. The applied liquid chromatography coupled to low- and high-resolution mass spectrometry (LC-HRMS-MS) provided detailed information on the structure in the MS(n) mode particularly with high resolution. For the analysis of the human samples, the LC separation had to be improved markedly allowing the separation of SG and its metabolites from its diastereomer MG and its metabolites. In analogy to MG, besides SG, nine phase I and eight phase II metabolites could be identified in rat urine, but only three phase I and five phase II metabolites in human urine. These differences may be caused by the lower SG dose applied by the user of Kratom preparations. SG and its metabolites could be differentiated in the human samples from the diastereomeric MG and its metabolites comparing the different retention times determined after application of the single alkaloids to rats. In addition, some differences in MS(2) and/or MS(3) spectra of the corresponding diastereomers were observed.

MeSH terms

  • Animals
  • Chromatography, Liquid / methods*
  • Humans
  • Male
  • Metabolic Networks and Pathways
  • Mitragyna / chemistry*
  • Plant Extracts / chemistry
  • Plant Leaves / chemistry
  • Rats
  • Rats, Wistar
  • Secologanin Tryptamine Alkaloids / chemistry
  • Secologanin Tryptamine Alkaloids / metabolism
  • Secologanin Tryptamine Alkaloids / urine*
  • Stereoisomerism
  • Tandem Mass Spectrometry / methods*

Substances

  • Plant Extracts
  • Secologanin Tryptamine Alkaloids
  • mitragynine