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Use of liquid chromatography coupled to low- and high-resolution linear ion trap mass spectrometry for studying the metabolism of paynantheine, an alkaloid of the herbal drug Kratom in rat and human urine

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Abstract

The Thai medicinal plant Mitragyna speciosa (Kratom in Thai) is misused as a herbal drug of abuse. During studies on the main Kratom alkaloid mitragynine (MG) in rats and humans, several dehydro analogs could be detected in urine of Kratom users, which were not found in rat urine after administration of pure MG. Questions arose as to whether these compounds are formed from MG only by humans or whether they are metabolites formed from the second abundant Kratom alkaloid paynantheine (PAY), the dehydro analog of MG. Therefore, the aim of the presented study was to identify the phase I and II metabolites of PAY in rat urine after administration of the pure alkaloid. This was first isolated from Kratom leaves. Liquid chromatography–linear ion trap mass spectrometry provided detailed structure information of the metabolites in the MSn mode particularly with high resolution. Besides PAY, the following phase I metabolites could be identified: 9-O-demethyl PAY, 16-carboxy PAY, 9-O-demethyl-16-carboxy PAY, 17-O-demethyl PAY, 17-O-demethyl-16,17-dihydro PAY, 9,17-O-bisdemethyl PAY, 9,17-O-bisdemethyl-16,17-dihydro PAY, 17-carboxy-16,17-dihydro PAY, and 9-O-demethyl-17-carboxy-16,17-dihydro PAY. These metabolites indicated that PAY was metabolized via the same pathways as MG. Several metabolites were excreted as glucuronides or sulfates. The metabolism studies in rats showed that PAY and its metabolites corresponded to the MG-related dehydro compounds detected in urine of the Kratom users. In conclusion, PAY and its metabolites may be further markers for a Kratom abuse in addition of MG and its metabolites.

Isolation of paynantheine from kratom leaves; high-resolution mass spectrum of the glucuronide of its 9-O-demethyl metabolite, and paynantheine structure with marked sides of biotransformation.

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Acknowledgments

The authors like to thank their colleagues Markus R. Meyer, Gabriele Ulrich, and Carsten Schröder as well as Kornelia Weidemann and Edeltraud Thiry, ThermoFisher Scientific, Scientific Instruments, Dreieich (Germany) for their support.

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Authors and Affiliations

  1. Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421, Homburg (Saar), Germany

    Anika A. Philipp, Dirk K. Wissenbach, Armin. A. Weber & Hans H. Maurer

  2. Department of Pharmaceutical Biology, Saarland University, 66123, Saarbrücken, Germany

    Josef Zapp

  3. Department of Forensic Medicine, Johannes Gutenberg University, 55131, Mainz, Germany

    Siegfried W. Zoerntlein

  4. Bureau of Drug and Narcotics, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000, Thailand

    Jidapha Kanogsunthornrat

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  1. Anika A. Philipp
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Correspondence to Hans H. Maurer.

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Philipp, A.A., Wissenbach, D.K., Weber, A.A. et al. Use of liquid chromatography coupled to low- and high-resolution linear ion trap mass spectrometry for studying the metabolism of paynantheine, an alkaloid of the herbal drug Kratom in rat and human urine. Anal Bioanal Chem 396, 2379–2391 (2010). https://doi.org/10.1007/s00216-009-3239-1

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  • DOI: https://doi.org/10.1007/s00216-009-3239-1

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