Quantification of trabectedin in human plasma: Validation of a high-performance liquid chromatography-mass spectrometry method and its application in a clinical pharmacokinetic study

Monique Zangarini, Laura Ceriani, Federica Sala, Elena Marangon, Renzo Bagnati, Maurizio D'Incalci, Federica Grosso, Massimo Zucchetti

Research output: Contribution to journalArticle

Abstract

A rapid, sensitive and specific HPLC-MS/MS method was developed and validated for the quantification of trabectedin in human plasma after using deuterated trabectedin as Internal Standard (IS). After the addition of ammonium sulphate, the analyte was extracted from human plasma with acidified methanol (0.1M HCl). Chromatographic separation was done on an Accucore XL C18 column (4μm; 50mm×2.1mm) using a Mobile Phase (MP) consisting of CH3COONH4 10mM, pH 6.8 (MP A) and CH3OH (MP B). The mass spectrometer worked with electrospray ionization in positive ion mode and Selected Reaction Monitoring (SRM), using target ions at [M-H2O+H]+ m/z 744.4 for trabectedin and [M-H2O+H]+ m/z 747.5 for the IS. The standard curve was linear (R2≥0.9955) over the concentration range 0.025-1.0ng/ml and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy determined on three quality control samples (0.04, 0.08 and 0.80ng/ml) were 81% and the lower limit of quantification 0.025ng/ml. The method was successfully applied to study trabectedin pharmacokinetics in a patient with a liposarcoma who received 1.3mg/m2 as a 24h continuous i.v. infusion.

Original languageEnglish
Pages (from-to)107-112
Number of pages6
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume95
DOIs
Publication statusPublished - 2014

Keywords

  • HPLC-MS/MS
  • Human plasma
  • Liposarcoma
  • Pharmacokinetics
  • Trabectedin

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Spectroscopy
  • Clinical Biochemistry
  • Medicine(all)

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