Abstract |
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.
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Authors | Peng Wang, Y-J Shi, Roy Helmy, Robert Reamer, Anant Vailaya |
Journal | Rapid communications in mass spectrometry : RCM
(Rapid Commun Mass Spectrom)
Vol. 19
Issue 24
Pg. 3749-54
( 2005)
ISSN: 0951-4198 [Print] England |
PMID | 16308847
(Publication Type: Journal Article)
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Copyright | 2005 John Wiley & Sons, Ltd. |
Chemical References |
- 6-(nitrooxy)hexyl-(2z)-4-(acetyloxy)-3-(4-(methylsulfonyl)phenyl)-2-phenylbut-2-enoate
- Butyrates
- Lactones
- Nitro Compounds
- Sulfones
- rofecoxib
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Topics |
- Butyrates
(chemistry)
- Chromatography, Liquid
(methods)
- Color
- Drug Contamination
- Lactones
(chemistry)
- Mass Spectrometry
(methods)
- Molecular Structure
- Nitro Compounds
(chemistry)
- Oxidation-Reduction
- Sulfones
(chemistry)
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