title: Norethindrone acetate (NA) and ethinyl estradiol (EE) related oxidative transformation products in stability samples of formulated drug product: synthesis of authentic references.
abstract: Preparative chemical methods for the synthesis of eight oxidative transformation products of ethinyl estradiol (EE) and norethindrone acetate (NA) are described. The prepared materials are useful as reference materials and standards for pharmaceutical analysis of EE and NA as bulk chemical or in formulated product. All eight products result from oxidation of the A and/or B rings of the parent compounds. Oxidation of the heteroannular 3,5 dienyl acetate derivative of NA resulted in the 6 alpha-hydroxy, 6 beta-hydroxy and 6-keto NA. Oxidation of 6-keto NA led to the preparation of 6 alpha-hydroxy, 6 beta-hydroxy, 6-keto- and Delta(6) EE. Delta(11) EE was prepared from estrone.
authors.affiliation: Department of Chemical Research and Development, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.
authors.forename: I Victor
authors.initials: IV
authors.lastname: Ekhato
authors.forename: Tim
authors.initials: T
authors.lastname: Hurley
authors.forename: Michael
authors.initials: M
authors.lastname: Lovdahl
authors.forename: T J
authors.initials: TJ
authors.lastname: Revitte
authors.forename: Luyi
authors.initials: L
authors.lastname: Guo
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.forename: Scott
authors.initials: S
authors.lastname: Clipper
authors.forename: Charles
authors.initials: C
authors.lastname: Colson
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004997:Ethinyl Estradiol / Q000032:analysis* / Q000737:chemistry*; D006900:Hydroxylation; D007664:Ketosteroids / Q000737:chemistry; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000032:analysis* / Q000737:chemistry*; D000077563:Norethindrone Acetate; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012015:Reference Standards
chemical_list: D007664:Ketosteroids; D004364:Pharmaceutical Preparations; D004997:Ethinyl Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone