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

• Published in: Journal of liquid chromatography & related technologies 2006-12, Vol.29 (20), p.2957-2974
• Main Authors: Solassol, I., Bressolle, F., Philibert, L., Charasson, V., Astre, C., Pinguet, F.
• Format: Article
• Language: English
• Subjects: Analytical chemistry; Chemistry; Chromatographic methods and physical methods associated with chromatography; Exact sciences and technology; Human plasma; Imatinib; Liquid-chromatography/electrospray ionization mass spectrometry method; N-desmethyl-imatinib; Other chromatographic methods; Quantitation
• ISSN: 1082-6076; 1520-572X
• DOI: 10.1080/10826070600981058

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-D 8 ) 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-D 8 , 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.