Investigation of conjugated metabolites of 4-hydroxyandrost-4-ene-3,17-dione in patient urine by liquid chromatography-atmospheric pressure ionization mass spectrometry
Poon, G.K.; Chui, Y.C.; Jarman, M.; Rowlands, M.G.; Kokkonen, P.S.; Niessen, W.M.; van der Greef, J.
Drug Metabolism and Disposition the Biological Fate of Chemicals 20(6): 941-947
1992
ISSN/ISBN: 0090-9556 PMID: 1362950 Document Number: 403214
Metabolism of the anticancer drug 4-hydroxyandrost-4-ene,3,17-dione (4OHA) was studied in cancer patients by HPLC-MS-MS. 4OHA was administered orally to a breast cancer patient. The drug was extensively metabolized and was excreted in the urine as the 4OHA-glucuronide, 3-alpha-hydroxy-5-beta-androstan-4,17-dione (3-alpha-OHA)-sulfate (or 4-hydroxytestosterone-sulfate) and 3-alpha,17-dihydroxy-5-beta-androstan-4-one (3,17-OHA)-sufate conjugates in the 4 hr posttreatment sample. Other metabolites include 4OHA-sulfate, 3-alpha-OHA-glucuronide, and 3,17-OHA-monoglucuronide. When 4OHA was given to the prostatic cancer patients intramuscularly, different metabolites were observed as compared with the female studies. The most noticeable difference is the absence of 4OHA-sulfate in both 24 and 48 hr posttreatment urine samples. The drug was eliminated mainly as 4OHA-glucuronide, 3-alpha-OHA-disulfate, and 3,17-OHA-monosulfate. Other metabolites that have been detected include 3-alpha-OHA-glucuronide, 3,17-OHA-glucuronide, 3,17-OHA-disulfate, and an unknown metabolite. The variation observed in metabolism could be attributed to a different route of drug administration (oral and intramuscular) and sex difference among the patients. This study describes the utilization of HPLC-MS-MS for monitoring the 4OHA conjugates and provides the first evidence that the presence of 4OHA-sulfate and its analogs in patient urinary extracts.