Cross-validation of a mass spectrometric-based method for the therapeutic drug monitoring of irinotecan: implementation of matrix-assisted laser desorption/ionization mass spectrometry in pharmacokinetic measurements

Eleonora Calandra, Bianca Posocco, Sara Crotti, Elena Marangon, Luciana Giodini, Donato Nitti, Giuseppe Toffoli, Pietro Traldi, Marco Agostini

Research output: Contribution to journalArticle

Abstract

Irinotecan is a widely used antineoplastic drug, mostly employed for the treatment of colorectal cancer. This drug is a feasible candidate for therapeutic drug monitoring due to the presence of a wide inter-individual variability in the pharmacokinetic and pharmacodynamic parameters. In order to determine the drug concentration during the administration protocol, we developed a quantitative MALDI-MS method using CHCA as MALDI matrix. Here, we demonstrate that MALDI-TOF can be applied in a routine setting for therapeutic drug monitoring in humans offering quick and accurate results. To reach this aim, we cross validated, according to FDA and EMA guidelines, the MALDI-TOF method in comparison with a standard LC-MS/MS method, applying it for the quantification of 108 patients’ plasma samples from a clinical trial. Standard curves for irinotecan were linear (R2 ≥ 0.9842) over the concentration ranges between 300 and 10,000 ng/mL and showed good back-calculated accuracy and precision. Intra- and inter-day precision and accuracy, determined on three quality control levels were always

Original languageEnglish
Pages (from-to)5369-5377
Number of pages9
JournalAnalytical and Bioanalytical Chemistry
Volume408
Issue number19
DOIs
Publication statusPublished - Jul 1 2016

Keywords

  • Bioanalytical methods
  • Drug monitoring/drug screening
  • Irinotecan
  • MALDI-TOF

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry

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