Isolation and characterization of urinary metabolites of arbaprostil in the rat.

The urinary metabolites of arbaprostil-3H in the male rat were profiled, isolated, and purified. Their structures were deduced by gas chromatography/mass spectrometry (GC/MS) studies after conversion to the methyl ester-methoxime-trimethylsilyl ether derivatives, aided by GC with simultaneous radioactivity monitoring. The identified metabolites accounted for over 91% of the urinary excretion products. beta-oxidation of the carboxy side-chain of arbaprostil to 15-methyl-tetranor PGE1 appeared to be the most significant metabolic pathway. Conversion to the dinor A and B derivatives and further beta-oxidation of these to the 15-methyl-tetranor A and B metabolites also appeared to occur. C-19-hydroxylated tetranor A and B derivatives of arbaprostil-3H were excreted in the urine. No conjugated urinary metabolites were evident.