PHARMACOKINETICS OF THE NEW THYROTROPIN-RELEASING-HORMONE ANALOG MONTIRELIN HYDRATE - 3RD COMMUNICATION - IDENTIFICATION OF METABOLITES IN RAT URINE

The metabolism of montirelin hydrate (CAS 90243-66-6, NS-3) was studie d in rats after intravenous administration of C-14-labeled or unlabele d NS-3. 1. Four radioactive metabolites (M-1 to M-4) were found in the urine after administration of C-14-NS-3. M-3 (major metabolite) and M -2 showed the same R(f) values as o-3-thiomorpholinyl]carbonyl]-L-hist idyl-L-proline (CNK-6004) and thyl-5-oxo-3-thiomorpholinyl]carbonyl]-L -histidine (CNK-6001), respectively. 2. M-3 and M-2 were purified from the urine after administration of unlabeled NS-3, and their chemical structures were identified by mass spectrometry, H-1-nuclear magnetic resonance spectroscopy, thin-layer chromatography and high performance liquid chromatography. Consequently, M-3 was identified as CNK-6004 f ormed by deamidation deprolination of CNK-6004.