Imatinib assay by high-performance liquid chromatography in tandem mass spectrometry with solid-phase extraction in human plasma

• Published in: Biomedical chromatography Vol. 27; no. 4; pp. 502 - 508
• Main Authors: Moreno, Jose María, Wojnicz, Aneta, Steegman, Juan Luis, Cano-Abad, Maria F., Ruiz-Nuño, Ana
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2013
• Subjects: Antineoplastic Agents - blood; Benzamides - blood; Chromatography, High Pressure Liquid - methods; chronic myeloid leukemia; Drug Monitoring - methods; Humans; imatinib; Imatinib Mesylate; isocratic; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Limit of Detection; liquid chromatography in tandem with mass spectrometry; Piperazines - blood; Protein Kinase Inhibitors - blood; Pyrimidines - blood; Solid Phase Extraction - methods; solid-phase extraction; Tandem Mass Spectrometry - methods; validation method
• ISSN: 0269-3879; 1099-0801
• DOI: 10.1002/bmc.2819

ABSTRACT We have developed a method of liquid chromatography in tandem with mass spectrometry to monitor therapeutic levels of imatinib in plasma, a selective inhibitor of protein tyrosine kinase. After solid‐phase extraction of plasma samples, imatinib and its internal standard, imatinib‐D8, were eluted with Zorbax SB‐C18 at 60 °C, under isocratic conditions through a mobile phase consisting of 4 mm ammonium formate, pH: 3.2 (solution A) and acetonitrile solution B. The flow rate was 0.8 mL/min with 55% solution A + 45% solution B. Imatinib was detected and quantified by mass spectrometry with electrospray ionization operating in selected‐reaction monitoring mode. The calibration curve was linear in the range 10–5000 ng/mL, the lower limit of quantitation being 10 ng/mL. The method was validated according to the recommendations of the Food and Drug Administration, including tests of matrix effect (bias < 10%) and recovery efficiency (>80 and <120%). The method is precise (coefficient of variance intra‐day <2% and inter‐day <7%), accurate (95–108%), sensitive and specific. It is a simple method with very fast recording time (1.2 min) that is applicable to clinical practice. This will permit improvement of the pharmacological treatment of patients. Copyright © 2012 John Wiley & Sons, Ltd.