Development and validation of and LC-MS/MS method to quantify Capmatinib in human plasma: Application to a pharmacokinetic study in rabbits

Siddhartha Lolla; Kumar Shiva Gubbiyappa

doi:10.7324/JAPS.2023.131969

Abstract

A novel, sensitive, and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of Capmatinib in human plasma and its pharmacokinetic application in rabbits. Chromatographic separation of the Capmatinib and internal standard ([13CD3]Capmatinib) were achieved on Phenomenex Luna C18 column (50 mm × 2 mm × 5 μm) with 0.5 ml/minute flow rate and coupled with API6000 triple quadrupole MS in multi reaction monitoring mode by applying mass transitions m/z 413.15–128.05 for Capmatinib and m/z 416.20–131.01 for the internal standard. The calibration curve exhibited linearity over the concentration of 1.0–28,000.0 ng/ml for Capmatinib. The LLOQ was 1.0 ng/ml. The validated LC-MS/MS method was effectively applied for the analysis of plasma in healthy rabbits for the determination of Capmatinib. From pharmacokinetic studies, Capmatinib showed an average AUClast of 12,964.14 ± 635.97 hour*ng/ml and Cmax of 2,537.94 ± 12.42 ng/ml in the subjects. In summary, the developed method has been successfully validated and pharmacokinetic parameters were demonstrated after oral administration of Capmatinib to healthy rabbits.

Keyword: Capmatinib non-small cell lung cancer LC-MS/ MS validation rabbits pharmacokinetics

Citation:

Lolla S, Gubbiyappa KS. Development and validation of and LC-MS/MS method to quantify Capmatinib in human plasma: Application to a pharmacokinetic study in rabbits. J Appl Pharm Sci, 2022. https://doi.org/10.7324/JAPS.2023.131969

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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