Synthesis and Quantitation of Genotoxic impurity 5-cyano-2-((4-fluorophenyl) (hydroxy) benzyl 4-methyl benzene sulfonate in Escitalopram Oxalate by RP-UPLC

Abstract

The objective of the research work is to synthesize potential genotoxic impurity 5-cyano-2-((4-fluorophenyl) (hydroxyl) benzyl 4-methyl benzene sulfonate and to develop suitable UPLC method to quantify the above genotoxicimpurity in Escitalopram Oxalate at 15 ppm level. The above genotoxic impurity was synthesized by regio selective tosyaltion of Diol compound, under controlled temperature conditions at 0-5C with TsCl/pyridine/chloroform and characterized. A new UPLC method was developed by using UPLC BEH Shield RP18 100 x 2.1 mm, 1.7 column. The mobile phase used is the mixture of 0.05% ortho phosphoric acid and acetonitrile in the ratio of 8:2 (v/v) as solvent-A and 3:7 (v/v) as solvent-B at a flow rate of 0.4 mL/minute. Detector wavelength monitored at 228nm and column temperature was maintained at 27C. The UPLC method was validated as per International conference on harmonization guidelines. This method is proven as highly sensitive with a detection limit of 5ppm and quantification limit of 15 ppm. Regression analysis showed that the correlation coefficient value of 0.99999. The accuracy of the method was established based on the recovery obtained for 5-cyano-2-((4-fluorophenyl) (hydroxyl) benzyl 4-methyl benzene sulfonate. The present research work provided the route of synthesis as well as an advanced analytical methodology to quantify the above critical Genotoxic impurity known as 5-cyano-2-((4-fluorophenyl) (hydroxyl) benzyl 4-methyl benzene sulfonate in Escitalopram oxalate.