Lapatinib is a novel, orally administered protein-tyrosine kinase inhibitor used in a treatment of patients with advanced or metastatic breast cancer. Considering the need for low-cost cancer treatments, it is essential to develop reliable and sensitive bioanalytical methods for lapatinib determination in human plasma for conducting bioequivalence studies of new generic drug products.

The aim of the study was to develop the first single quadrupole bioanalytical method for the determination of lapatinib in human plasma, which can be applied to pharmacokinetic studies after administration of 250 mg oral dose. The method was validated according to European Medicines Agency (EMA) [1] and Food and Drug Administration (FDA) [2] guidelines, in compliance with the principles of Good Laboratory Practice (GLP), providing its reliability. The sample preparation procedure was based on a liquid-liquid extraction with methyl tert-buthyl ether. Chromatographic analysis was carried out using C18 column and isocratic elution with mixture of acetonitrile, methanol and formic buffer. Positive electrospray ionization mass spectrometry in single ion monitoring mode was applied as a detector. Isotope labelled lapatinib was used as an internal standard.

All of the validation parameters met acceptance criteria. Calibration curve, prepared using freshly spiked plasma samples, was linear within the range of 5.00-800.00 ng/mL. The method was found to be sufficiently accurate and precise over the studied range of concentrations.

Lapatinib was synthesized in the Chemistry Department and Minisynthesis Department than certified in the R&D Analytical Chemistry Department of the Pharmaceutical Research Institute. The study was supported by the European Union (European Regional Development Fund) under the Innovative Economy Operational Programme 2007–2013 (Project No. UDA-POIG.01.03.01-14-069/08-00).

References:
[1]  Guideline on bioanalytical method validation. European Medicines Agency (EMEA/CHMP/EWP/192217/2009). London, 21 July 2011.
[2]  Guidance for Industry. Bioanalytical Method Validation. U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Center for Veterinary Medicine (CVM). May 2001.
 

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