title: Examination of rofecoxib solution decomposition under alkaline and photolytic stress conditions.
abstract: Rofecoxib is a highly active and selective cyclo-oxygenase II inhibitor. A stability-indicating method for the assay of rofecoxib has been developed using reverse-phase high-performance liquid chromatography (HPLC). Stress testing of rofecoxib was conducted during the method development and validation. HPLC analysis of rofecoxib solutions stressed under alkaline and photolytic conditions revealed the presence of several degradates. Two main degradates were determined to be the cyclization product formed by photo-cyclization and the dicarboxylate formed by ring opening in the presence of base and oxygen. The identities of these degradates were confirmed by comparison of UV spectra and HPLC retention time with the independently synthesized products. The mechanistic pathways for the formation of these degradates are discussed. Further improvement of the HPLC method's ruggedness has been made based on these studies.
authors.affiliation: Analytical Research, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA. bing_mao@merck.com
authors.forename: Bing
authors.initials: B
authors.lastname: Mao
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abrahim
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Ge
authors.forename: Dean K
authors.initials: DK
authors.lastname: Ellison
authors.forename: Robert
authors.initials: R
authors.lastname: Hartman
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Prabhu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Reamer
authors.forename: Jean
authors.initials: J
authors.lastname: Wyvratt
mesh_terms: D000468:Alkalies; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007783:Lactones / Q000737:chemistry*; D010782:Photolysis; D012996:Solutions; D013450:Sulfones
chemical_list: D000468:Alkalies; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007783:Lactones; D012996:Solutions; D013450:Sulfones; C116926:rofecoxib