LIQUID CHROMATOGRAPHY–MASS SPECTROMETRY/MASS SPECTROMETRY METHOD FOR THE DETERMINATION OF LAPATINIB IN RAT PLASMA: APPLICATION TO PHARMACOKINETIC STUDIES IN WISTAR RATS

NARMADA PALNATI; NALINI KOTAPATI; GOPAL VAIDYANATHAN

doi:10.22159/ajpcr.2021.v14i2.39660

Authors

NARMADA PALNATI Natco Pharma Limited, Natco Research Centre, B-13, Industrial Estate, Sanathnagar, Hyderabad, Telangana, India.
NALINI KOTAPATI Natco Pharma Limited, Natco Research Centre, B-13, Industrial Estate, Sanathnagar, Hyderabad, Telangana, India.
GOPAL VAIDYANATHAN Natco Pharma Limited, Natco Research Centre, B-13, Industrial Estate, Sanathnagar, Hyderabad, Telangana, India.

DOI:

https://doi.org/10.22159/ajpcr.2021.v14i2.39660

Keywords:

Lapatinib, Liquid chromatography-mass spectrometrymass spectrometry, Bioanalytical method validation, Pharmacokinetic study, Gefitinib, Rat plasma

Abstract

Objective: The objective of the study was to develop and validate a simple, accurate, and sensitive liquid chromatography–mass spectrometry (LC–MS)/MS method for the determination of lapatinib a dual tyrosine kinase inhibitor in rat plasma using gefitinib as internal standard.

Methods: An Inertsil ODS column (50 mm×4.6 mm×5 μm) was used for separation with isocratic elution of 10 mM ammonium formate-acetonitrile (5:95 v/v). Analyte and internal standard were extracted from 50 μl of plasma using tertiary butyl methyl ether followed by subsequent reconstitution in a mixture of water-acetonitrile.

Results: The extraction recoveries were 95% and 98% for lapatinib and gefitinib, respectively. The lower limit of quantification was 5 ng/ml with a precision of 6.2% and accuracy of 108%. The response was found to be linear over the range of 5–1000 ng/ml with a correlation coefficient of 0.999. The intraday and interday precision expressed as relative standard deviation was <15%.

Conclusion: This validated method was applied to the pharmacokinetic study in Wistar rats. The proposed bioanalytical LC–MS/MS method for lapatinib is a simple, sensitive, and accurate to quantify the concentrations in rat plasma.

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