Abstract

SIMPLE AND RAPID METHOD FOR THE QUANTIFICATION OF IMATINIB MESYLATE AND DESMETHYL IMATINIB IN HUMAN PLASMA USINGLC-MS/MS AND ITS APPLICATION TO ROUTINE THERAPEUTIC DRUG MONITORING

Jose Francis* Biswajit Dubashi Rajan Sundaram Suresh Chandra Pradhan Adithan, Chandrasekaran

Abstract

Introduction: Imatinib mesylate is the standard of care in the treatment of chronic myeloid leukemia. Therapeutic drug monitoring (TDM) can be used as a tool to cross-check treatment adherence or toxic manifestations to imatinib mesylate in chronic myeloid leukemia patients. The study aimed to develop a simple, cost effective and rapid method for quantification of imatinib mesylate and desmethyl imatinib in human plasma using LC-MS/MS. Methods: The biological samples were prepared by a simple protein precipitation method and separated using an XTerra MS C18 column. Imatinib and its metabolite desmethyl imatinib was quantified using multiple reaction monitoring (MRM) with a triple quadrupole tandem mass spectrometer working in the positive electrospray ionization (ESI+) mode using verapamil as internal standard. RESULTS: The method was validated and found to be precise and accurate within the dynamic range of 5ng-8μg/mLfor the drug and 5ng-1μg/mL for the metabolite. The method was then applied to routine therapeutic drug monitoring of CML patients and the mean±SD trough level concentration was found to be 1437±459 ng/mL. Therapeutic drug monitoring; Imatinib mesylate; Liquid chromatography-Mass spectrometry.

Keywords: Therapeutic drug monitoring; Imatinib mesylate; Liquid chromatography-Mass spectrometry.