Validated UHPLC-MS/MS assay for quantitative determination of etoposide, gemcitabine, vinorelbine and their metabolites in patients with lung cancer

Biomed Chromatogr. 2017 Nov;31(11). doi: 10.1002/bmc.3989. Epub 2017 Jun 15.

Abstract

A fully valid UHPLC-MS/MS method was developed for the determination of etoposide, gemcitabine, vinorelbine and their metabolites (etoposide catechol, 2',2'-difluorodeoxyuridine and 4-O-deacetylvinorelbine) in human plasma. The multiple reaction monitoring mode was performed with an electrospray ionization interface operating in both the positive and negative ion modes per compound. The method required only 100 μL plasma with a one-step simple de-proteinization procedure, and a short run time of 7.5 min per sample. A Waters ACQUITY UPLC HSS T3 column (2.1 × 100 mm, 1.8 μm) provided chromatographic separation of analytes using a binary mobile phase gradient (A, 0.1% formic acid in acetonitrile, v/v; B, 0.1% formic acid in water, v/v). Linear coefficients of correlation were >0.995 for all analytes. The relative deviation of this method was <10% for intra- and inter-day assays and the accuracy ranged between 86.35% and 113.44%. The mean extraction recovery and matrix effect of all the analytes were 62.07-105.46% and 93.67-105.87%, respectively. This method was successfully applied to clinical samples from patients with lung cancer.

Keywords: UHPLC-MS/MS; etoposide; gemcitabine; human plasma; metabolite; vinorelbine.

MeSH terms

  • Aged
  • Antineoplastic Agents / blood*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use
  • Chromatography, High Pressure Liquid / methods*
  • Cohort Studies
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / blood
  • Deoxycytidine / metabolism
  • Deoxycytidine / therapeutic use
  • Etoposide / blood*
  • Etoposide / metabolism
  • Etoposide / therapeutic use
  • Gemcitabine
  • Humans
  • Linear Models
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / metabolism
  • Middle Aged
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods*
  • Vinblastine / analogs & derivatives*
  • Vinblastine / blood
  • Vinblastine / metabolism
  • Vinblastine / therapeutic use
  • Vinorelbine

Substances

  • Antineoplastic Agents
  • Deoxycytidine
  • Vinblastine
  • Etoposide
  • Vinorelbine
  • Gemcitabine