Determination of the antitumor agent SOAz (1,3,3,5,5 pentakis(aziridino)-1 lambda 6,2,4,6,3 lambda 5, 5 lambda 5 thia-triazadiphosphorine-1-oxide) by a gas chromatographic assay suitable for pharmacokinetic studies in man.
A sensitive method, based on capillary gas chromatography using a thermionic detector, has been developed for the new antitumor agent pentakis(aziridino)-thiatriazadiphosphorine-oxide, (NPAz2)2NSOAz ('SOAz'), in order to obtain pharmacokinetic data from patients receiving this drug IV in clinical trials. A structural analog of SOAz, (NPAz2)2NSOPh ('SOPh'), was used as an internal standard. The detection limit of SOAz with this method was 0.01 mg/l for serum and 0.04 mg/l for urine. The coefficient of variation (n = 10) was 6,0% at 1.5 mg/l in serum and 1.6% at 75.0 mg/l in urine. Analytical recoveries averaged 89.9% from serum and 86.7% from urine. In two patients treated with subtoxic doses of SOAz (55 mg/m2), serum levels were found ranging from 3.0 to 0.16 mg/l at 10 min and 12 h, respectively, after administration. This assay seems to be useful for determining SOAz in samples from patients receiving subtoxic doses of SOAz.
D000368:Aged; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D001389:Azirines / Q000378:metabolism* / Q000627:therapeutic use; D002849:Chromatography, Gas; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D000970:Antineoplastic Agents; D001389:Azirines; C035161:pentazirinocyclodiphosphathiazene