Determination of Aplidin®, a marine-derived anticancer drug, in human plasma, whole blood and urine by liquid chromatography with electrospray ionisation tandem mass spectrometric detection

Nicola Celli, Barbara Mariani, Francesco Di Carlo, Massimo Zucchetti, Luis Lopez-Lazaro, Maurizio D'Incalci, Domenico Rotilio

Research output: Contribution to journalArticle

Abstract

A sensitive and highly specific liquid chromatographic method with electrospray ionisation tandem mass spectrometric detection (LC-ESI-MS/MS) is reported for the determination in human plasma, whole blood and urine of Aplidin® (APL), a novel depsipeptide derived from the tunicate Aplidium albicans with a potent cytotoxic activity under investigation in clinical studies. Didemnin B was used as internal standard and, after protein precipitation with acetonitrile and liquid-liquid extraction with chloroform, APL was separated by liquid chromatography using a reversed-phase C 18 column and a linear gradient of acetonitrile in water (both containing 0.5% formic acid). Detection was performed using a turboionspray source operated in positive ion mode and by multiple reaction monitoring (MRM; m/z 1111→295 for APL and m/z 1113→297 for didemnin B). The method was linear (r≥0.9933) over the range 1-250ng/ml, with intra- and inter-batch precision and accuracy below 12.2% (except at LLOQ, ≤15.4%) for both plasma and urine. Recoveries were moderate, ranging from 54 to 70% in plasma and blood, and from 46 to 60% in urine, for both APL and didemnin B. The LOD was 0.25ng/ ml for both matrices. APL resulted stable in the different matrices at least for 6h (both at room temperature and 37°C), after freeze and thaw cycles and long term storage at -20°C. The method allowed demonstrating that APL is in a dynamic equilibrium between plasma and blood cells. Moreover, the method was successfully applied to the pharmacokinetic study of Aplidin® in cancer patients.

Original languageEnglish
Pages (from-to)619-630
Number of pages12
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume34
Issue number3
DOIs
Publication statusPublished - Feb 18 2004

Keywords

  • Aplidin®
  • Cytotoxic drug
  • Didemnin B
  • Distribution in blood

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science

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