Prostacyclin metabolites in human plasma.

The major metabolites of prostacyclin (PGI2) in human plasma have been determined after intravenous infusion of tritium-labeled prostacyclin. Plasma was extracted and chromatographed. On high-pressure liquid chromatography (HPLC), several radioactive peaks could be resolved. The major peak containing 41.6% of the radioactivity had the retention volume of authentic 6-keto-prostaglandin F 1 alpha (6-keto-PGF 1 alpha), the stable in vitro hydrolysis product of prostacyclin. When the material of this peak was derivatized to the methoxime methyl ester trimethylsilyl ether and analyzed by gas chromatography-mass spectrometry, the fragments m/z 508 and 598, which are characteristic of this derivative of 6-keto-PFG 1 alpha were detected. A much smaller peak representing 6.6% of the radioactivity eluted from HPLC with the same retention volume as dinor-6, 15-diketo-13, 14-dihydro-PGF 1 alpha. On gas chromatography-mass spectrometry this material resulted in the fragments m/z 527, 468, 437, and 347, which are characteristic for this prostanoid. Finally, 10.1% of the radioactivity with ions m/z 571m 481, 391, and 354 on mass spectrometric analysis could be identified as dinor-6, 15-diketo-13, 14-dihydro-20-carboxyl-PGF 1 alpha. It is concluded that 6-keto-PFG 1 alpha represents the major breakdown product of prostacyclin in human plasma. In addition, dinor-6, 15-diketo-13, 14-dihydro-PGF 1 alpha and its w-oxidized analog could be identified circulating metabolites.