Back to Search
Start Over
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
- Source :
- Journal of Analytical Science and Technology, Vol 11, Iss 1, Pp 1-9 (2020)
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 20933371
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of Analytical Science and Technology
- Accession number :
- edsair.doi.dedup.....931e63afc5955f5235b810840dd80cad