IN-VIVO METABOLISM OF THE VITAMIN-D ANALOG, 22-OXACALCITRIOL - EVIDENCE FOR SIDE-CHAIN TRUNCATION AND 17-HYDROXYLATION

After intravenous administration of the vitamin D-3 analog, 22-oxacalc itriol (OCT), to normal rats plasma metabolites were investigated by H PLC, GC-MS and LC-MS. Five side-chain oxidation metabolites, 24R(OH)OC T, 24S(OH)OCT, (25R)-26(OH)OCT, (25S)-26(OH)OCT and 24oxoOCT, were ide ntified by comparison with the corresponding synthetic compounds. Thes e side-chain oxidation metabolites were similar to those of calcitriol [1 alpha,25(OH)(2) vitamin D-3] described previously. Besides these f ive metabolites, two unique side-chain cleavage metabolites, 20S(OH)-h exanol-OCT and 17,20S(OH)(2)-hexanor-OCT, were identified as main meta bolites in plasma by CC-MS and LC-MS using a specific chemical reactio n. Our studies suggest that OCT is extensively metabolized and circula tes in blood as a number of metabolites as well as unchanged OCT. This metabolism includes both unique pathways of C-23-O-22 cleavage and 17 -hydroxylation, in addition to the side-chain oxidation metabolites si milar to those of 1 alpha,25-(OH)(2)D-3. (C) 1998 Elsevier Science Ltd . All rights reserved.