Simple and Sensitive Methods for the Determination of 2-(4′-Chloromethyl phenyl) Benzonitrile and 2-(4′-Bromomethyl phenyl) Benzonitrile Contents in Valsartan Drug Substance by Gas Chromatography

Simple and reliable gas chromatographic methods were developed, optimized, and validated for the determination of 2-(4′-chloromethyl phenyl) benzonitrile (2-CMPB) and 2-(4′-bromomethyl phenyl) benzonitrile (2-BMPB) contents in valsartan drug substance, using benzophenone as internal standard (IS). Efficient chromatographic separations were achieved on DB-1, 30 m length with 0.53 mm i.d., and 3 μm particle diameter column consists of 100% dimethyl polysiloxane as a stationary phase by passing helium as a carrier gas. The analytes were extracted in dichloromethane and monitored by flame ionization detector. The performance of these methods was assessed by evaluating specificity, precision, sensitivity, linearity, and accuracy. The limits of detection (LOD) and limits of quantification (LOQ) established for 2-CMPB are 0.10 μg mL−1 and 0.32 μg mL−1, respectively. For 2-BMPB, LOD is 0.31 μg mL−1 and LOQ is 0.95 μg mL−1. The average recoveries for 2-CMPB are in the range of 96.8% to 106.7% and for 2-BMPB (LOQ level) are 99.3%. The methods can be successfully applied for the routine analysis of valsartan drug substance.