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Identification of a trace colored impurity in drug substance by preparative liquid chromatography and mass spectrometry
Author(s) -
Wang Peng,
Shi Y.J.,
Helmy Roy,
Reamer Robert,
Vailaya Anant
Publication year - 2005
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.2261
Subject(s) - chemistry , impurity , colored , mass spectrometry , high performance liquid chromatography , chromatography , liquid chromatography–mass spectrometry , double bond , tandem mass spectrometry , organic chemistry , materials science , composite material
6‐(Nitrooxy)hexyl‐(2z)‐4‐(acetyloxy)‐3‐[4‐(methylsulfonyl)phenyl]‐2‐phenylbut‐2‐enoate (enoate 1) was investigated as a novel therapy for pain relief. In a recent manufacturing run at the pilot plant scale, the enoate drug substance was found to have a yellowish color not observed previously. An unknown impurity at trace level was detected by high‐performance liquid chromatographic (HPLC) analysis and found to be the primary cause for the color of the drug substance. The colored impurity was enriched by preparative HPLC and structurally elucidated by liquid chromatography/tandem mass spectrometry (LC/MS/MS). It was found that the colored impurity was derived from the product of oxidative dimerization of rofecoxib, an impurity present in the enoic acid intermediate. It was further revealed by the photodiode array and LC/MS/MS data that the colored impurity exists in the drug substance as a pair of double‐bond isomers with one isomer at majority. These findings were also confirmed by synthesizing the colored impurity through the proposed pathway. Copyright © 2005 John Wiley & Sons, Ltd.