Liquid Chromatography‐Electrospray Mass Spectrometry Determination of Imatinib and Its Main Metabolite, N‐Desmethyl‐Imatinib in Human Plasma

Abstract

The aim of this paper was to develop a specific and sensitive liquid chromatography/electrospray ionization mass spectrometry method for the determination of imatinib and its metabolite in human plasma. The method involved a solid phase extraction of the compounds and internal standard (imatinib‐D₈) from human plasma. LC separation was performed on a SymmetryShield™ RP8 column with a mobile phase of water:acetonitrile:formic acid. MS data were acquired in single ion monitoring mode at m/z 494.4, m/z 480.4 and m/z 502.4 for imatinib, N‐desmethyl‐imatinib, and imatinib‐D₈, respectively. The absence of ion suppression was demonstrated. The drug/internal standard peak area ratios were linked via a quadratic relationship to plasma concentrations (8.35–8350 µg/L for imatinib and N‐desmethyl‐imatinib). Precision was 2.8–10.8% and accuracy was 91.3–111.3%. Extraction recoveries were ≥70%. The lower limit of quantitation was 8.35 µg/L for both imatinib and N‐desmethyl‐imatinib.

Keywords:

• Imatinib
• N‐desmethyl‐imatinib
• Liquid‐chromatography/electrospray ionization mass spectrometry method
• Quantitation
• Human plasma

Acknowledgments

The authors gratefully acknowledge support of this work by the “Ligue Nationale de Lutte contre le Cancer”, Montpellier, France. Special thanks are given to B. Hawkins, for his assistance in the preparation of this manuscript.