Simultaneous quantitation of azole antifungals, antibiotics, imatinib, and raltegravir in human plasma by two-dimensional high-performance liquid chromatography-tandem mass spectrometry

J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Mar 1:919-920:1-9. doi: 10.1016/j.jchromb.2012.12.028. Epub 2013 Jan 9.

Abstract

High-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a standard analytical technique for therapeutic drug monitoring (TDM). A rapid LC-MS/MS method was developed for simultaneous quantitation of 3 antifungals and one active metabolite (posaconazole, voriconazole, itraconazole, and hydroxy-itraconazole), 5 antibiotics (daptomycin, ciprofloxacin, oxacillin, levofloxacin, and rifampicin), an antineoplastic agent (imatinib), and an antiretroviral (raltegravir) in human plasma. Protein precipitation of 10 μL of plasma with acetonitrile was used as a single-extraction procedure. After 2-dimensional LC, all drugs were quantified by electrospray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection in the positive mode. The method was validated per FDA recommendations including the study of extraction recovery (from 79.3% to 105.9%) and matrix effect via ion suppression/enhancement phenomenon. This method is precise (intra- and inter-assay coefficients of variation of 1.95-12.77%, 2.56-8.16% and 2.12-11.38% for low, medium and high levels of internal quality controls respectively) and accurate (intra- and inter-assay biases of 0.19-12.67%, 0.04 to -12.17% and 0.22-12.98% respectively). This method is an efficient tool for routine TDM and optimization of laboratory resource utilization.

MeSH terms

  • Anti-Bacterial Agents / blood*
  • Antifungal Agents / blood*
  • Antineoplastic Agents / blood
  • Azoles / blood*
  • Benzamides / blood*
  • Chromatography, High Pressure Liquid / methods*
  • Drug Stability
  • Humans
  • Imatinib Mesylate
  • Least-Squares Analysis
  • Limit of Detection
  • Piperazines / blood*
  • Pyrimidines / blood*
  • Pyrrolidinones / blood*
  • Raltegravir Potassium
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antineoplastic Agents
  • Azoles
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Pyrrolidinones
  • Raltegravir Potassium
  • Imatinib Mesylate