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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.

A specific GC method has been developed, optimized and validated for the determination of seven related substances namely N,N-dimethyl valpronamide, valeric acid, 2-methyl valeric acid, 2-ethyl valeric acid, 2-isopropyl valeric acid, 2-n-butyl valeric acid and 2-propyl-2-pentenoic acid in divalproex sodium (DPS) drug substance. Chromatographic separations of these seven impurities were achieved on DB-FFAP column (30 m × 0.53 mm, 1.0 μm), which consists nitroterephthalic acid modified polyethylene glycol material as stationary phase. DPS is a coordination complex of the sodium valproate and valproic acid (VPA). Nonanoic acid is used as internal standard. All the seven related substances, VPA and nonanoic acid were extracted into dichloromethane and monitored by GC with flame ionization detector. The performance of the developed method was assessed by evaluating specificity, linearity, sensitivity, precision, accuracy and robustness. Forced degradation experiments were conducted to evaluate the degradation behavior of DPS. The established limits of detection (LODs) and limits of quantification (LOQs) values for the related substances were in the ranges of 4-5 and 12-15 μg mL-1, respectively. Further, for VPA, LOD and LOQ values were 4 and 12 μg mL-1, respectively. The correction factors of these related substances with respect to VPA and lie between 0.92 and 1.44. The average recoveries were in the range of 92.4-108.4%.

A simple and reliable gas chromatography method has been developed and validated for the determination of 3-quinuclidinol content in solifenacin succinate drug substance, using dimethylsulfoxide (DMSO) as internal standard (IS). Efficient chromatographic separation was achieved on DB-Wax, 15 m long with 0.53 mm i.d., 1.0 µm particle diameter column consists with 100% polyethylene glycol as stationary phase including carrier gas as Helium. The analyte and internal standard were extracted in chloroform and monitored by flame ionization detector. The performance of the method was assessed by evaluating specificity, precision (repeatability, reproducibility), linearity, robustness and accuracy. No interference of organic solvents used in the synthesis was observed. The proposed method has a potential application to drug substances which may contains 3-quinuclidinol. The limits of detection (LOD) and limits of quantification (LOQ) established for 3-quinuclidinol, 40 µg g-1 and 120 µg g-1 respectively. The correlation coefficient value of linearity experiment is 0.9997. The average recovery for 3-quinuclidinol is 100.8%. The results proves that the validated method was suitable for determining 3-quinuclidinol content and method can be successfully applied for the routine analysis of solifenacin succinate drug substance.

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