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Quantitative bioanalytical assay for the tropomyosin receptor kinase inhibitor larotrectinib in mouse plasma and tissue homogenates using liquid chromatography-tandem mass spectrometry
- Source :
- Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1102-1103, 167. Elsevier
- Publication Year :
- 2018
-
Abstract
- Larotrectinib is a promising tyrosine kinase inhibitor for solid tumors harboring tropomyosin receptor kinase gene fusions. A bioanalytical assay was developed for this drug in small volume samples using a 96-well format to efficiently support multiple mouse studies. The assay was completely validated for mouse plasma and partially for homogenates of eight different tissues: brain, heart, kidneys, liver, lungs, small intestine, spleen, and testes. Proteins in 10-μl samples were precipitated using acetonitrile containing momelotinib as internal standard. Chromatographic separation of analyte and internal standard from endogenous interferences was performed on an ethylene bridged octadecyl silica column using 0.1% (v/v) formic acid (in water) and methanol for gradient elution. Electrospray ionization and selected reaction monitoring on a triple quadrupole mass spectrometer were used for detection. In the range 1–2000 ng/ml the drug could be quantified in all 9 matrices with precisions (within-day and between-day) in the range 2.7–11.1% and accuracies in the range 87.4–101.4%. Compounds were sufficiently stable under all investigated conditions except for kidney homogenate. A pilot pharmacokinetic and tissue distribution study in mice demonstrated the applicability of the new presented assay for larotrectinib.
- Subjects :
- Male
Analyte
Bioanalysis
Formic acid
Electrospray ionization
Clinical Biochemistry
Sensitivity and Specificity
01 natural sciences
Biochemistry
Analytical Chemistry
Mice
03 medical and health sciences
chemistry.chemical_compound
Plasma
0302 clinical medicine
Pharmacokinetics
Tandem Mass Spectrometry
Liquid chromatography–mass spectrometry
Animals
Humans
Tissue Distribution
LC-MS/MS
Protein Kinase Inhibitors
Larotrectinib
Chromatography
Chemistry
010401 analytical chemistry
Selected reaction monitoring
Reproducibility of Results
General Medicine
Cell Biology
Mouse tissue
0104 chemical sciences
Triple quadrupole mass spectrometer
Pyrimidines
030220 oncology & carcinogenesis
Linear Models
Pyrazoles
Female
Protein Kinases
Chromatography, Liquid
Subjects
Details
- Language :
- English
- ISSN :
- 15700232
- Database :
- OpenAIRE
- Journal :
- Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
- Accession number :
- edsair.doi.dedup.....b18086d5e31f6a5ca1ed84742e23295a