title: Studies on the metabolism of mitragynine, the main alkaloid of the herbal drug Kratom, in rat and human urine using liquid chromatography-linear ion trap mass spectrometry.
abstract: Mitragynine (MG) is an indole alkaloid of the Thai medicinal plant Mitragyna speciosa (Kratom in Thai) and reported to have opioid agonistic properties. Because of its stimulant and euphoric effects, Kratom is used as a herbal drug of abuse. The aim of the presented study is to identify the phase I and II metabolites of MG in rat and human urine after solid-phase extraction (SPE) using liquid chromatography-linear ion trap mass spectrometry providing detailed structure information in the MSn mode particularly with high resolution. The seven identified phase I metabolites indicated that MG was metabolized by hydrolysis of the methylester in position 16, O-demethylation of the 9-methoxy group and of the 17-methoxy group, followed, via the intermediate aldehydes, by oxidation to carboxylic acids or reduction to alcohols and combinations of some steps. In rats, four metabolites were additionally conjugated to glucuronides and one to sulfate, but in humans, three metabolites to glucuronides and three to sulfates.
authors.affiliation: Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, D-66421 Homburg (Saar), Germany.
authors.forename: Anika A
authors.initials: AA
authors.lastname: Philipp
authors.forename: Dirk K
authors.initials: DK
authors.lastname: Wissenbach
authors.forename: Siegfried W
authors.initials: SW
authors.lastname: Zoerntlein
authors.forename: Oliver N
authors.initials: ON
authors.lastname: Klein
authors.forename: Jidapha
authors.initials: J
authors.lastname: Kanogsunthornrat
authors.forename: Hans H
authors.initials: HH
authors.lastname: Maurer
mesh_terms: D053000:Analytic Sample Preparation Methods; D000818:Animals; D001192:Arylsulfatases / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D008297:Male; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D053858:Metabolic Networks and Pathways; D032065:Mitragyna; D015394:Molecular Structure; D010936:Plant Extracts / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D018515:Plant Leaves; D051381:Rats; D017208:Rats, Wistar; D046948:Secologanin Tryptamine Alkaloids / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D052616:Solid Phase Extraction / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D015813:Substance Abuse Detection / Q000379:methods; D053719:Tandem Mass Spectrometry
chemical_list: D010936:Plant Extracts; D046948:Secologanin Tryptamine Alkaloids; D001192:Arylsulfatases; D005966:Glucuronidase; C001801:mitragynine