Norethindrone acetate (NA) and ethinyl estradiol (EE) related oxidative transformation products in stability samples of formulated drug product: synthesis of authentic references.
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.
Ekhato
I Victor
IV
Department of Chemical Research and Development, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.
Hurley
Tim
T
Lovdahl
Michael
M
Revitte
T J
TJ
Guo
Luyi
L
Huang
Yun
Y
Clipper
Scott
S
Colson
Charles
C
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
D007664:Ketosteroids; D004364:Pharmaceutical Preparations; D004997:Ethinyl Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone