Development and validation of an LC-MS/MS method for monitoring larotrectinib, a tropomyosin-related kinase inhibitor, in mouse and human plasma and application to pharmacokinetic studies
| Autor: | Yoon-Jee Chae, Jong Soon Kang, Kyeong-Ryoon Lee, Yoo-Kyung Song, Song-Hee Chae, Tae-Sung Koo, Jae Young Lee, Min Ju Kim |
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| Rok vydání: | 2020 |
| Předmět: |
Formic acid
lcsh:Analytical chemistry General Physics and Astronomy 01 natural sciences General Biochemistry Genetics and Molecular Biology lcsh:Chemistry 03 medical and health sciences chemistry.chemical_compound Pharmacokinetics Oral administration Protein precipitation General Materials Science Receptor Tyrosine Kinase Gene Receptor Larotrectinib 030304 developmental biology General Environmental Science 0303 health sciences lcsh:QD71-142 Chromatography Mass spectrometry 010401 analytical chemistry Selected reaction monitoring General Chemistry 0104 chemical sciences lcsh:QD1-999 chemistry Trk receptor TRK inhibitor |
| Zdroj: | Journal of Analytical Science and Technology, Vol 11, Iss 1, Pp 1-9 (2020) |
| ISSN: | 2093-3371 |
| DOI: | 10.1186/s40543-020-00219-5 |
| Popis: | Larotrectinib is an orally administered drug and the first and only selective pan-tropomyosin receptor kinase (TRK) inhibitor in clinical development to treat cancer patients harboring a neurotrophic receptor tyrosine kinase gene fusion. In this study, an analytical method to quantify the TRK inhibitor in mouse and human plasma was developed and validated using LC-MS/MS following protein precipitation with acetonitrile. Larotrectinib and an internal standard (carbamazepine) were separated from endogenous substances using an Xterra C18 column with acetonitrile containing 0.1% formic acid as the mobile phase. The ions m/z 429.8 → 342.8 for larotrectinib and m/z 237.0 → 194.0 for carbamazepine detected in multiple reaction monitoring mode were used for the quantitation. The detector response of larotrectinib was linear within the concentration range 5–10,000 ng/mL with a correlation coefficient (r2) of not less than 0.999. The intra- and inter-day precision and accuracy were less than 10.48% and within − 8.99%, respectively, in mouse and human plasma. Larotrectinib was stable under various storage and handling conditions, and no significant matrix effect was observed in both mouse and human plasma. Finally, the assay was successfully applied to the pharmacokinetic study of larotrectinib after its intravenous and oral administration to mice. |
| Databáze: | OpenAIRE |
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