Determination of total and lactone form of a new camptothecin derivative gimatecan (ST1481) and its metabolite ST1698 in human plasma by high-performance liquid chromatography with fluorimetric detection

Silvia Pace, Francesca Capocasa, Carlo Tallarico, Roberta Frapolli, Massimo Zucchetti, Antonio Longo

Research output: Contribution to journalArticle

Abstract

A new sensitive high-performance liquid chromatographic (HPLC) method for the determination of gimatecan (ST1481), a new camptothecin derivative, and its metabolite (ST1698) in plasma sample has been developed. The method consisted of on-line column solid phase extraction of analytes from human plasma, chromatographic separation by isocratic elution, then fluorimetric detection. The limits of quantitation were 0.25 ng/mL for both the analytes. The recovery of the extraction procedure was in the range of 62.8-71.1% for all the compounds. Good linearity (R2 > 0.999) was observed within the calibration ranges studied: 0.25-25 ng/mL for both ST1481 and ST1698. Precision was in the range 1.2-4.3%, and accuracy was always lower than 4.7%. Surprisingly, after administration of ST1481 to humans, plasma concentrations found were higher than expected, while metabolite plasma concentrations were negligible. For this reason, a second calibration curve range was validated to quantify ST1481 in human plasma, ranging from 5 to 200 ng/mL. A good accuracy and precision were obtained, confirming the usefulness of the procedure. By using neutral analytical condition the intact lactone form was estimated in plasma samples from a patient. The lactone form amounted to 80-100% of the total ST1481.

Original languageEnglish
Pages (from-to)507-514
Number of pages8
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume50
Issue number3
DOIs
Publication statusPublished - Oct 15 2009

Keywords

  • Gimatecan
  • High-performance liquid chromatography
  • Lactone form
  • Online extraction
  • Oral camptothecin

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Spectroscopy
  • Clinical Biochemistry

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