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 language | English |
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Pages (from-to) | 399-401 |
Number of pages | 3 |
Journal | Journal of Pharmaceutical Sciences |
Volume | 78 |
Issue number | 5 |
Publication status | Published - 1989 |
ASJC Scopus subject areas
- Molecular Medicine
- Chemistry(all)
- Organic Chemistry
- Drug Discovery
- Pharmaceutical Science
- Pharmacology