A sensitive and specific assay for pentamethylmelamine in plasma: applicability to clinical studies.
A sensitive and specific procedure for measuring plasma levels of pentamethylmelamine (PMM), a chemotherapeutic agent currently undergoing phase I trials, has been developed. PMM was isolated (recovery greater than 95%) from 3-ml plasma samples by cation exchange chromatography followed by solvent extraction, and was quantitated by selected ion monitoring with a gas chromatograph/mass spectrometer. Deuterium-labeled PMM was synthesized and used as an internal standard; standard curves were prepared by plotting m/e 196/199 ratios versus concentrations, and were linear in the range of 0.05-50.0 microM. The coefficient of variation for repeated measurements was less than 1% at all concentrations studied. To test the applicability of this method to clinical studies, plasma clearances of PMM were measured in two studies in each of three cancer patients receiving 80-mg/m2 doses of PMM as 1-hour iv infusions. Peak plasma concentrations, observed immediately after the end of the infusions, averaged 4.1 microM (SE = 0.6 microM). Plasma elimination was found to be biphasic; a short initial half-life (approximately 27 minutes) was followed by a longer elimination half-life of 133 minutes (SE = 35 minutes). Measurements in two patients indicated that less than 0.1% of the administered PMM was excreted unchanged in the urine in 24 hours, suggesting that hepatic metabolism of PMM may be a major contributor to plasma clearance of the drug in man.
D000368:Aged; D006585:Altretamine / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism / Q000494:pharmacology / Q000652:urine; D000970:Antineoplastic Agents / Q000097:blood*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood; D012015:Reference Standards; D014227:Triazines / Q000097:blood*
D000970:Antineoplastic Agents; D014227:Triazines; D006585:Altretamine; C022048:pentamethylmelamine