Chemical instability of 15-keto-13,14-dihydro-PGE2: the reason for low assay reliability.
The spontaneous degradation of 15-keto-13,14-dihydro-PGE2 was studied under various conditions. In aqueous media, dehydration rapidly occurred, particularly at high or very low pH. The acid catalyzed dehydration product was identified as 15-keto-13,14-dihydro-PGA2. This compound was also formed at alkaline pH, however, at higher pH a bicyclic compound, 11-deoxy-13,14-dihydro-15-keto-11,16-cyclo-PGE2, was formed in addition (cf. Fig. 1). The amounts of the latter compound increased with time and with increasing pH. In samples containing albumin, 15-keto-dihydro-PGE2 was degraded even more rapidly than in buffer of the same pH. In addition to the formation of the dehydration products, a considerable part of the metabolite was bound to albumin to yield water soluble adducts. A similar binding occurred to a low molecular weight fraction of plasma. The compound that was bound was 15-keto-dihydro-PGA2, whereas both 15-keto-dihydro-PGE2 and the bicyclic product were relatively inert in this respect. Due to its chemical stability, the bicyclic degradation product, 11-deoxy-13,14-dihydro-15-keto-11,16-cyclo-PGE2, is suggested as a suitable target for measurements instead of the labile parent compound, 15-keto-dihydro-PGE2, or the reactive dehydration product, 15-keto-dihydro-PGA2.
D000143:Acids; D000478:Alkylation; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone / Q000031:analogs & derivatives*; D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D011454:Prostaglandins A; D011458:Prostaglandins E / Q000097:blood; D012995:Solubility; D013439:Sulfhydryl Reagents
D000143:Acids; D011454:Prostaglandins A; D011458:Prostaglandins E; D013439:Sulfhydryl Reagents; C025087:15-keto-13,14-dihydroprostaglandin E2; C025088:11-deoxy-15-keto-13,14-dihydro-11 beta,16-cycloprostaglandin E2; C025558:15-keto-13,14-dihydroprostaglandin A2; D015232:Dinoprostone