1. Quantitation of ivosidenib in human plasma via LC–MS/MS and its application in clinical trials
- Author
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Shaoxia Yu, Heidi Mangus, Guowen Liu, Rohini Narayanaswamy, Erin McCourt, and Feng Yin
- Subjects
Bioanalysis ,Pyridines ,Clinical Biochemistry ,Glycine ,Molecular Conformation ,Analytical Chemistry ,Matrix (chemical analysis) ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Tandem Mass Spectrometry ,In vivo ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Racemization ,030304 developmental biology ,Clinical Trials as Topic ,0303 health sciences ,Chromatography ,Chemistry ,General Medicine ,Small molecule ,Clinical trial ,Medical Laboratory Technology ,Isocitrate dehydrogenase ,030220 oncology & carcinogenesis ,Chromatography, Liquid - Abstract
Aim: Ivosidenib is a potent and selective small molecule inhibitor of mutant isocitrate dehydrogenase 1. Accurate measurement of ivosidenib is the key to ivosidenib pharmacokinetics in clinical trials. Materials & methods: Quantitation of ivosidenib was conducted by using a stable isotope labeled compound (ivosidenib-d4) as the internal standard. Results: This assay was validated and successfully applied to support multiple clinical trials. Selected clinical samples were also tested by a chiral LC–MS/MS method against four ivosidenib isomer standards to exclude the possibility of in vivo racemization of ivosidenib. Conclusion: A robust LC–MS/MS method was validated for ivosidenib in human plasma. This is the first time for ivosidenib bioanalytical method in any human matrix to be reported.
- Published
- 2021