Examination of rofecoxib solution decomposition under alkaline and photolytic stress conditions

被引：17

作者：

Mao, B

Abrahim, A

Ge, Z

Ellison, DK

Hartman, R

Prabhu, SV

Reamer, RA

Wyvratt, J

机构：

[1] Merck Res Labs, Analyt Res, Rahway, NJ 07065 USA

[2] Merck Res Labs, Proc Res, Rahway, NJ 07065 USA

来源：

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS | 2002年 / 28卷 / 06期

关键词：

rofecoxib; base-decomposition; photodecomposition; stability;

D O I：

10.1016/S0731-7085(01)00716-6

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

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. (C) 2002 Elsevier Science B.V. All rights reserved.

引用

页码：1101 / 1113

页数：13

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