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

Biomed Chromatogr. 2013 Apr;27(4):502-8. doi: 10.1002/bmc.2819. Epub 2012 Oct 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Antineoplastic Agents / blood*
  • Benzamides / blood*
  • Chromatography, High Pressure Liquid / methods*
  • Drug Monitoring / methods
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Limit of Detection
  • Piperazines / blood*
  • Protein Kinase Inhibitors / blood*
  • Pyrimidines / blood*
  • Solid Phase Extraction / methods*
  • Tandem Mass Spectrometry / methods*

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate