Temperature and pH-Dependent Stability of Mitragyna Alkaloids

J Anal Toxicol. 2020 May 18;44(4):314-324. doi: 10.1093/jat/bkz103.

Abstract

Mitragynine (MG) is the principal psychoactive alkaloid in kratom. The drug produces a variety of dose-dependent effects that appeal to recreational drug users and individuals seeking therapeutic benefits in the absence of medical supervision. In light of documented intoxications, hospitalizations and fatalities, MG and other alkaloids from Mitragyna speciosa are of growing importance to the forensic toxicology community. However, the chemical stability of these compounds has not been thoroughly described. In this report, the stability of MG, 7-hydroxymitragynine (MG-OH), speciociliatine (SC), speciogynine (SG) and paynantheine (PY) are investigated. Short-term stability of the Mitragyna alkaloids was determined over a range of pH (2-10) and temperature (4-80°C) over 8 hours. Liquid chromatography--quadrupole/time-of-flight mass spectrometry was used to estimate half-lives and identify degradation products where possible. The stability of MG and other alkaloids was highly dependent on pH and temperature. All of the Mitragyna alkaloids studied were acid labile. Under alkaline conditions, MG undergoes chemical hydrolysis of the methyl ester to produce 16-carboxymitragynine. MG-OH was the most unstable alkaloid studied, with significant drug loss at 8 hours experienced at temperatures of 40°C and above. No significant drug losses were observed for MG in aqueous solution (pH 2-10) at 4, 20 or 40°C. Diastereoisomers of MG (SC and SG) demonstrated even greater stability. These findings are discussed within the context of the identification of Mitragyna alkaloids in toxicological specimens.

MeSH terms

  • Alkaloids / chemistry*
  • Chromatography, Liquid
  • Drug Stability*
  • Forensic Toxicology*
  • Humans
  • Hydrogen-Ion Concentration
  • Indole Alkaloids
  • Mitragyna*
  • Oxindoles
  • Plant Extracts*
  • Secologanin Tryptamine Alkaloids

Substances

  • Alkaloids
  • Indole Alkaloids
  • Oxindoles
  • Plant Extracts
  • Secologanin Tryptamine Alkaloids
  • paynantheine
  • speciogynine
  • 7-hydroxymitragynine
  • mitragynine