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Journal of Chromatography B

Journal of Chromatography B

IF: 2.8
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Bioanalytical assay for the new-generation ROS1/TRK/ALK inhibitor repotrectinib in mouse plasma and tissue homogenate using liquid chromatography-tandem mass spectrometry

Published:1 May 2020 DOI: 10.1016/j.jchromb.2020.122098 PMID: 32278292
Wenlong Li , Nikoletta Perpinioti , Alfred H. Schinkel , Jos H. Beijnen , Rolf W. Sparidans

Abstract

Repotrectinib, a next-generation ROS1/TRK/ALK tyrosine kinase inhibitor, overcomes resistance due to acquired solvent-front mutations involving ROS1, NTRK1-3, and ALK. A bioanalytical assay for quantification of repotrectinib in mouse plasma and seven tissue-related matrices (brain, liver, spleen, kidney, small intestinal tissue, small intestinal content, and testis homogenates) was developed and validated using liquid chromatography with tandem mass spectrometric detection in a high-throughput 96-well format. Protein precipitation was performed by adding acetonitrile, also containing the internal standard axitinib, to 10-μl samples for all matrices. Chromatographic separation of analytes was done on an ACQUITY UPLC? BEH C18 column by gradient elution using ammonium hydroxide in water and methanol. Compounds were monitored with positive electrospray ionization using a triple quadruple mass spectrometer in selected reaction monitoring mode. The method was successfully validated in the 1–1000?ng/ml calibration range. Precisions (intra- and interday) were in the range of 1.3–8.7% and accuracies were in between 90.5% and 107.3% for all levels in all matrices. The developed method was successfully applied to investigate the plasma pharmacokinetics and tissue accumulation of repotrectinib in wild-type mice.

Substances (10)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Repotrectinib 1802220-02-5 C18H18FN5O2 192 suppliers $8.00-$1600.00
Repotrectinib 1802220-02-5 C18H18FN5O2 192 suppliers $8.00-$1600.00
Repotrectinib 1802220-02-5 C18H18FN5O2 192 suppliers $8.00-$1600.00
Repotrectinib 1802220-02-5 C18H18FN5O2 192 suppliers $8.00-$1600.00
TPX-0005 1802220-02-5 - Inquiry
TPX-0005 1802220-02-5 - Inquiry
TPX-0005 1802220-02-5 - Inquiry
TPX-0005 1802220-02-5 - Inquiry
TPX-0005 1802220-02-5 C18H18FN5O2 - Inquiry
TPX-0005 1802220-02-5 C18H18FN5O2 - Inquiry
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