title: Synthesis of multiply deuterated 3- and 21-monosulfates of allo-tetrahydrocorticosteroids as internal standards for mass spectrometry.
abstract: The accurate analysis of trace components in complex biological matrices requires the use of reliable internal standards. For liquid chromatography/mass spectrometry analysis, the stable isotope-labeled analogues of the analyte molecules are the most appropriate internal standards. In this paper the synthesis of the 3- and 21-monosulfates of allo-tetrahydrocorticosteroids labeled with four or five deuterium atoms is described. The principal reactions used were (1) hydrogen-deuterium exchange reaction of active methylene groups adjacent to 3- and 11-oxo group of 17,20;20,21-bismethylenedioxy derivatives of 5α-3-ketosteroids and/or 5α-11-ketosteroids with NaOD in CH(3)OD followed by reduction with NaBD(4), (2) epimerization of the 3β-hydroxy group into a 3α configuration, (3) sulfation of hydroxy groups at C-3 or C-21 in the resulting substrates with sulfur trioxide-trimethylamine complex, and (4) removal of 17,20;20,21-bismethylenedioxy groups with hydrogen fluoride in ethanol. Isotopic purity was found to be satisfactory by MS, and NMR properties of the new compounds were tabulated. The labeled compounds can be used as internal standards in liquid chromatography/mass spectrometry assays for clinical and biochemical studies.
authors.affiliation: Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-osaka 577-8502, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Mitamura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Mabuchi
authors.forename: Kaori
authors.initials: K
authors.lastname: Nagae
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakajima
authors.forename: Rina
authors.initials: R
authors.lastname: Matsumoto
authors.forename: Sachi
authors.initials: S
authors.lastname: Fujioka
authors.forename: Kanta
authors.initials: K
authors.lastname: Sato
authors.forename: Rika
authors.initials: R
authors.lastname: Satoh née Okihara
authors.forename: Takashi
authors.initials: T
authors.lastname: Iida
authors.forename: Shoujiro
authors.initials: S
authors.lastname: Ogawa
authors.forename: Alan F
authors.initials: AF
authors.lastname: Hofmann
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000305:Adrenal Cortex Hormones / Q000138:chemical synthesis* / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D013058:Mass Spectrometry / Q000592:standards*; D012015:Reference Standards; D013431:Sulfates / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000305:Adrenal Cortex Hormones; D013431:Sulfates