Extraction of Labelled WR-158,122 from Rat and Monkey Urine and Bile. Initial Studies.

Urine and bile samples from control untreated rats and rhesus monkeys as well as from bile duct ligated BiDuLi rats and bile duct cannulated BiDuCa rats and monkeys treated with WR-158,122-14C have been extracted with a series of organic solvents in an attempt to define the profile of biliary and urinary metabolites. Extraction of a urine sample from a BiDuCa monkey demonstrated that when the urine was saturated with KBr very polar solvents such as n- propanol NPRO, pyridine, dimethylformamide or methanol formed one phase with some salt and the solvent phase contained all or nearly all of the 14c activity. Solvents forming 2 phases such as ethylene dichloride 2-ethyl-hexanol 82, EDC-2EH, ethyl acetate, acetonitrile ACN or tetrahydrofuran THF extracted increasing amounts of 14C-containing metabolites ranging from 8.3 to 66.2. NPRO, EDC-2EH, ACN and THF extracted all or nearly all of the 14c activity from control simian urine and bile and from control rat urine. EDC-2EH, ACN and THF extracted increasing amounts of 14C from a 72 hr monkey treatment bile but even THF extracted only 27 of the total 14C content. The total parent drug in this sample was 3 or less. The 14C activity in a 12 hr treatment bile sample from a BiDuCa rat gave an extraction profile not much different from that obtained with simian treatment bile less than 4 of the activity comprised parent drug.