A gas chromatographic mass spectrometric assay for the determination of aphidicolin in plasma of cancer patients.
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 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)trifluoracetamide as sililating agent, pyridine, and trimethylchlorosilane, and allowed to react at 80 degrees 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 I 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 (beta) half-life of 2 h.
Rotondo
S
S
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Zucchetti
M
M
Sessa
C
C
D'Incalci
M
M
Benfenati
E
E
Fanelli
R
R
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000097:blood*; D016590:Aphidicolin; D002849:Chromatography, Gas; D004224:Diterpenes / Q000008:administration & dosage / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood*
D000903:Antibiotics, Antineoplastic; D004224:Diterpenes; D016590:Aphidicolin