Development and validation of a LC-MS/MS method for the determination of the novel oral 1,14 substituted taxane derivatives, IDN 5738 and IDN 5839, in mouse plasma and its application to the pharmacokinetic study

Elena Marangon, Cristiano Falcioni, Carla Manzotti, Gabriele Fontana, Maurizio D'Incalci, Massimo Zucchetti

Research output: Contribution to journalArticlepeer-review

Abstract

Two LC-ESI-MS and CID-MS/MS methods were developed and validated for pharmacokinetic studies of the novel oral taxane derivatives IDN 5738 and IDN 5839, used for preclinical evaluation in mice. The analysis requires 100 μL of plasma sample, involves the addition of an internal standard and protein precipitation with 0.1% HCOOH in acetonitrile. The HPLC separation was obtained on Sunfire C18 column and Selected Reaction Monitoring technique was used to quantify the taxanes. The recoveries were more than 90%; the methods were linear over the validated concentrations range of 25-1500 ng/mL for IDN 5738 and 25-5000 ng/mL for IDN 5839 and had a limit of detection of 0.14 and 0.25 ng/mL, respectively. The inter-day coefficient of variation (CV%) of the calibration standards ranged between 1.3 and 7.2% for IDN 5738 and between 0.0 and 9.0% for IDN 5839 and the mean accuracy was in the range 85.3-112.0% for IDN 5738 and between 80.0 and 111.0% for IDN 5839. Moreover, analysing quality control plasma samples on three different days, the methods resulted precise and accurate showing intra- and inter-day CV within 12% for both analytes, and accuracy of 92.0-113.3% and 85.9-105.7% for IDN 5738 and IDN 5839, respectively. With these methods, we studied for the first time, the pharmacokinetics of the two taxanes showing for both, good oral bioavailability (>50%).

Original languageEnglish
Pages (from-to)4147-4153
Number of pages7
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume877
Issue number32
DOIs
Publication statusPublished - Dec 15 2009

Keywords

  • LC-ESI-MS and CID-MS/MS method development
  • Oral taxanes
  • Preclinical pharmacokinetics
  • SRM analysis

ASJC Scopus subject areas

  • Biochemistry
  • Analytical Chemistry
  • Cell Biology
  • Clinical Biochemistry

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