Temperature and pH-Dependent Stability of Mitragyna Alkaloids

Mitragynine 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, mitragynine 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 mitragynine (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 degrees C) over 8 h. Liquid chromatography time-of-flight mass spectrometry (LC-Q/TOF-MS) was used to estimate half-lives and identify degradation products where possible. The stability of mitragynine and other alkaloids was highly dependent on pH and temperature. All of the Mitragyna alkaloids studied were acid labile. Under alkaline conditions mitragynine undergoes chemical hydrolysis of the methyl ester to produce 16-carboxymitragynine. 7-Hydroxymitragynine was the most unstable alkaloid studied, with significant drug loss at 8 hours experienced at temperatures of 40 degrees C and above. No significant drug losses were observed for mitragynine in aqueous solution (pH 2-10) at 4, 20 or 40 degrees C. Diastereoisomers of mitragynine (speciociliatine and speciogynine) demonstrated even greater stability. These findings are discussed within the context of the identification of Mitragyna alkaloids in toxicological specimens.