Analysis of aplidine (dehydrodidemnin B), a new marine-derived depsipeptide, in rat biological fluids by liquid chromatography-tandem mass spectrometry

Nicola Celli, Agata Motos Gallardo, Cosmo Rossi, Massimo Zucchetti, Maurizio D'Incalci, Domenico Rotilio

Research output: Contribution to journalArticle

Abstract

Aplidine (dehydrodidemnin B) is a new marine-derived depsipeptide with a powerful cytotoxic activity, which is under early clinical investigation in Europe and in the US. In order to investigate the pharmacokinetic properties of this novel drug, an HPLC-tandem mass spectrometry method was developed for the determination of aplidine in biological samples. Didemnin B, a hydroxy analogue, was used as internal standard. After protein precipitation with acetonitrile and extraction with chloroform, aplidine was chromatographed with a RP octadecylsilica column using a water-acetonitrile linear gradient in the presence of formic acid at the flow-rate of 500 μl/min. The method was linear over a 5-100 ng/ml range (LOD=0.5 ng/ml) in plasma and over a 1.25-125 ng/ml range (LOD=0.2 ng/ml) in urine with precision and accuracy below 14.0%. The intra- and inter-day precision and accuracy were below 12.5%. The extraction procedure recoveries for aplidine and didemnin B were 69% and 68%, respectively in plasma and 91% and 87%, respectively in urine. Differences in linearity, LOQ, LOD and recoveries between plasma and urine samples seem to be matrix-dependent. The applicability of the method was tested by measuring aplidine in rat plasma and urine after intravenous treatment. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)335-343
Number of pages9
JournalJournal of Chromatography B: Biomedical Sciences and Applications
Volume731
Issue number2
DOIs
Publication statusPublished - Aug 27 1999

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Keywords

  • Aplidine
  • Depsipeptide
  • Didemnin

ASJC Scopus subject areas

  • Chemistry(all)

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