Simultaneous quantification of seventeen kratom alkaloids and metabolites in human plasma and its application to clinical pharmacokinetic sample analysis.

Authors

Siva Rama Raju Kanumuri, Manoj Gundeti, Sushobhan Mukhopadhyay, Naftali Z Zeilinger, C Austin Zamarripa, Kirsten E Smith, Christopher R McCurdy, Abhisheak Sharma

Published in

Pharmaceutical biology. Volume 64. Issue 1. Pages 902-920. Epub Aug 17, 2026.

Abstract

Mitragyna speciosa Korth, commonly known as kratom, has been used traditionally in Southeast Asia by chewing fresh leaves and brewing decoctions (tea) for its stimulant and sedative-like properties. Despite its widespread use, controlled clinical trials are limited and have monitored mitragynine only or a few other major alkaloids and metabolites.
The objective of the study was to develop and validate an ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of 12 kratom alkaloids along with 5 metabolites of mitragynine in human plasma.
A sensitive UPLC-MS/MS based bioanalytical method for the simultaneous quantification of kratom alkaloids, including mitragynine, speciogynine, speciociliatine, mitraciliatine, paynantheine, isopaynantheine, corynantheidine, corynoxine-A, corynoxine-B, mitraphylline, speciofoline, and ajmalicine, along with five metabolites of mitragynine, 7-hydroxymitragynine, 9-hydroxycorynantheidine, mitragynine 16-carboxylic acid, mitragynine pseudoindoxyl, and 3-dehydromitragynine in human plasma was developed and validated following FDA guidelines. Chemically unstable metabolites, 7-hydroxymitragynine and 9-hydroxycorynantheidine, were stabilized in human plasma. The bioanalytical method was further used for the analysis of plasma samples collected during a clinical trial involving four regular kratom users.
The method was linear over the concentration range of 1-250 ng/mL. A simple protein precipitation method was used to extract analytes. Upon oral administration of kratom products, most of the alkaloids were absorbed quickly and showed peak plasma concentrations within 1-2 h post-dose.
Mitragynine, speciociliatine, mitraciliatine, isopaynantheine, and paynantheine are major circulating alkaloids, with mitragynine 16-carboxylic acid and 9-hydroxycorynantheidine being the major circulating metabolites of mitragynine in plasma upon kratom oral administration.

PMID:
42605611
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.

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