Cristina Sempio, Jorge Campos-Palomino, Jelena Klawitter, Wanzhu Zhao, Marilyn A Huestis, Uwe Christians, Jost Klawitter
{"title":"Quantification of 11 kratom alkaloids including mitragynine and its main metabolites in human plasma using LC-MS/MS.","authors":"Cristina Sempio, Jorge Campos-Palomino, Jelena Klawitter, Wanzhu Zhao, Marilyn A Huestis, Uwe Christians, Jost Klawitter","doi":"10.1007/s00216-024-05689-9","DOIUrl":null,"url":null,"abstract":"<p><p>Recently in the USA, kratom consumers increasingly report use of the plant for self-treatment of mood ailments, the lack of energy, chronic pain, and opioid withdrawal and dependence. Several alkaloids are present in kratom leaves, but limited data are available on their pharmacokinetics/pharmacodynamics, except for mitragynine. To support clinical studies, a high-performance liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of 11 kratom alkaloids in human plasma was developed and validated. For calibration standards and quality control samples, human plasma was fortified with alkaloids at varying concentrations, and 200 µL were extracted employing a simple one-step protein precipitation procedure. The extracts were analyzed using LC-MS/MS including electrospray ionization (ESI) in positive multiple reaction monitoring (MRM) mode. The lower limit of quantification was 0.5 ng/mL, and the upper limit of quantification was 400 ng/mL for all analytes. Inter-day analytical accuracy and imprecision ranged from 98.4 to 113% of nominal and from 3.9 to 14.7% (coefficient of variance), respectively. The analysis of plasma samples collected during a clinical trial administering capsules containing kratom leaf extract showed that most samples had quantifiable concentrations of mitragynine, 7-OH-mitragynine, speciogynine, speciociliatine, and paynantheine and that mitragynine, speciogynine, and speciociliatine accumulated in human plasma after daily administration over 15 days. An LC-MS/MS assay for the specific quantification of kratom alkaloids including mitragynine and its main metabolites was developed and successfully validated in human plasma. Human plasma samples collected following multiple oral administrations of a controlled Kratom extract documented accumulation of kratom alkaloids over 15 days.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Analytical and Bioanalytical Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s00216-024-05689-9","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Recently in the USA, kratom consumers increasingly report use of the plant for self-treatment of mood ailments, the lack of energy, chronic pain, and opioid withdrawal and dependence. Several alkaloids are present in kratom leaves, but limited data are available on their pharmacokinetics/pharmacodynamics, except for mitragynine. To support clinical studies, a high-performance liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of 11 kratom alkaloids in human plasma was developed and validated. For calibration standards and quality control samples, human plasma was fortified with alkaloids at varying concentrations, and 200 µL were extracted employing a simple one-step protein precipitation procedure. The extracts were analyzed using LC-MS/MS including electrospray ionization (ESI) in positive multiple reaction monitoring (MRM) mode. The lower limit of quantification was 0.5 ng/mL, and the upper limit of quantification was 400 ng/mL for all analytes. Inter-day analytical accuracy and imprecision ranged from 98.4 to 113% of nominal and from 3.9 to 14.7% (coefficient of variance), respectively. The analysis of plasma samples collected during a clinical trial administering capsules containing kratom leaf extract showed that most samples had quantifiable concentrations of mitragynine, 7-OH-mitragynine, speciogynine, speciociliatine, and paynantheine and that mitragynine, speciogynine, and speciociliatine accumulated in human plasma after daily administration over 15 days. An LC-MS/MS assay for the specific quantification of kratom alkaloids including mitragynine and its main metabolites was developed and successfully validated in human plasma. Human plasma samples collected following multiple oral administrations of a controlled Kratom extract documented accumulation of kratom alkaloids over 15 days.
期刊介绍:
Analytical and Bioanalytical Chemistry’s mission is the rapid publication of excellent and high-impact research articles on fundamental and applied topics of analytical and bioanalytical measurement science. Its scope is broad, and ranges from novel measurement platforms and their characterization to multidisciplinary approaches that effectively address important scientific problems. The Editors encourage submissions presenting innovative analytical research in concept, instrumentation, methods, and/or applications, including: mass spectrometry, spectroscopy, and electroanalysis; advanced separations; analytical strategies in “-omics” and imaging, bioanalysis, and sampling; miniaturized devices, medical diagnostics, sensors; analytical characterization of nano- and biomaterials; chemometrics and advanced data analysis.