A gas chromatographic-mass 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 he)tane:isopropanol (1 0:l) 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)trifluo- roacelamide 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 f SD of aphidicolin from plasma was 73.5 f 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 I clinical trials of aphidicolin-17-glycinate administered as a 1-h iv infusion. Two patients received dose of 290 mg/mz and the third received 435 mgim'. Aphidicolin plasma levels at the end of infusion were very low, and the drug rinpidly disappeared from pllasma with a terminal (p) half-life of 2 h.
Aphidicolin (NSC 2347140 i s a tetracyclic diterpenoid antibiotic derived from the fungi Cephalosporiurn aphidicolal and Nigrospora sphaerica.2 It possesses interesting biochemical and pharmacological properties and i s an inhibitor of DNA polymerase (Y w i t h antivira13s4 and antineoplastic activities.!' The antitumoral activity o f aphidicolin observed against some rodent tumors5 has stimulated interest in clinical investigations to ae8sess the potential effectiveness of this compound against human tumors. The poor water sola Non-small cell lung cancer.