Isolation, synthesis and characterization of impurities in celecoxib, a COX-2 inhibitor.
During the impurity profile of Celecoxib, four polar impurities (impurity I, II, III and IV) and one non-polar impurity (impurity V) with respect to Celecoxib were detected by HPLC. LC-MS has been employed in this impurity profile study. The three polar impurities (I, II and III) were found to be process related while impurities (IV and V) turned out to be isomers. The impurities III, IV and V were isolated with the help of preparative HPLC. The structure of impurities III, IV (ortho-isomer) and V (regio-isomer) were confirmed as [5-(4-methylphenyl)-3-trifluoromethyl-1H-pyrazole], 4-[5-(2'-methyl phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide, and 4-[4-(4'-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide, respectively. The structures of impurities I, II, III and IV were confirmed by synthesis and structural characterization using spectral data. However, the impurity V was not synthesized.
Satyanarayana
U
U
Department of Analytical Research, Discovery Research, Dr. Reddy's Laboratories Ltd., Bollaram Road, Miyapur, Hyderabad 500049, India.
Rao
D Sreenivas
DS
Kumar
Y Ravindra
YR
Babu
J Moses
JM
Kumar
P Rajender
PR
Reddy
J Tirupathi
JT
D000068579:Celecoxib; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000302:isolation & purification*; D004340:Drug Contamination; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D013058:Mass Spectrometry / Q000379:methods; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000302:isolation & purification*; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000302:isolation & purification*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib