title: Pharmacokinetics of the new thyrotropin releasing hormone analogue montirelin hydrate. 3rd communication: identification of metabolites in rat urine.
abstract: The metabolism of montirelin hydrate (CAS 90243-66-6, NS-3) was studied in rats after intravenous administration of 14C-labeled or unlabeled NS-3. 1. Four radioactive metabolites (M-1 to M-4) were found in the urine after administration of 14C-NS-3. M-3 (major metabolite) and M-2 showed the same Rf values as (-)-N-[[(3R,6R)-6-methyl-5-oxo-3-thiomorpholinyl]carbonyl]-L-histi dyl-L- proline (CNK-6004) and (+)-N-[[(3R,6R)-6-methyl-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, 1H-nuclear magnetic resonance spectroscopy, thin-layer chromatography and high performance liquid chromatography. Consequently, M-3 was identified as CNK-6004 formed by deamidation at a prolinamide moiety of NS-3, and M-2 as CNK-6001 formed by deprolination of CNK-6004.
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: A
authors.initials: A
authors.lastname: Okita
authors.forename: A
authors.initials: A
authors.lastname: Morino
mesh_terms: D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D008401:Gas Chromatography-Mass Spectrometry; D006639:Histidine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009025:Morpholines / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000652:urine
chemical_list: D007202:Indicators and Reagents; D009025:Morpholines; C102906:CNK 6001; C031926:montirelin; D006639:Histidine; D013973:Thyrotropin-Releasing Hormone