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

  • 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.

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.

Keywords: Lapatinib, Liquid chromatography–mass spectrometry/mass spectrometry, Bioanalytical method validation, Pharmacokinetic study, Gefitinib, Rat plasma

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PALNATI, N., N. KOTAPATI, and G. VAIDYANATHAN. “LIQUID CHROMATOGRAPHY–MASS SPECTROMETRY/MASS SPECTROMETRY METHOD FOR THE DETERMINATION OF LAPATINIB IN RAT PLASMA: APPLICATION TO PHARMACOKINETIC STUDIES IN WISTAR RATS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 14, no. 2, Jan. 2021, pp. 74-77, doi:10.22159/ajpcr.2021.v14i2.39660.
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