A gas chromatographic mass spectrometric assay for the determination of aphidicolin in plasma of cancer patients

S. Rotondo, M. Zucchetti, C. Sessa, M. D'Incalci, E. Benfenati, R. Fanelli

Research output: Contribution to journalArticlepeer-review

Abstract

A gas chromatographic-spectrometric (GC-MS) method is described for the determination of the novel anticancer agent aphidicolin in plasma. The extraction was carried out in a solvent mixture of hexane:isopropanol (10:1) and the external standard aphidicolane was added after evaporation of the organic phase. The residue was then redissolved in a derivatizing mixture containing bis(trimethylsilyl)trifluoroacetamide as sililating agent, pyridine, and trimethylchlorosilane, and allowed to react at 80°C for 2 h. After GC separation of the derivatized samples, selected ion recording analysis was done, monitoring the ions at mass 523.3 and 448.3 for aphidicolin and aphidicolane, respectively. The mean recovery ±SD of aphidicolin from plasma was 73.5±11.6% in the range from 5 to 800 ng. This method was applied to determine aphidicolin plasma levels in three cancer patients in Phase 1 clinical trials of aphidicolin-17-glycinate administered as a 1-h iv infusion. Two patients received dose of 290 mg/m2 and the third received 435 mg/m2. Aphidicolin plasma levels at the end of infusion were very low, and the drug rapidly disappeared from plasma with a terminal (β) half-life of 2 h.

Original languageEnglish
Pages (from-to)399-401
Number of pages3
JournalJournal of Pharmaceutical Sciences
Volume78
Issue number5
Publication statusPublished - 1989

ASJC Scopus subject areas

  • Molecular Medicine
  • Chemistry(all)
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Pharmacology

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