Method development and validation study for quantitative determination of 2-chloromethyl-3,4-dimethoxy pyridine hydrochloride a genotoxic impurity in pantoprazole active pharmaceutical ingredient (API) by LC/MS/MS.

A sensitive and selective liquid chromatographic-tandem mass spectrometric (LC/MS/MS) method was developed and validated for the trace analysis (>1 ppm level) of 2-chloromethyl-3,4-dimethoxy pyridine hydrochloride a genotoxic impurity in pantoprazole sodium drug substances. LC/MS/MS analysis of 2-chloromethyl-3,4-dimethoxy pyridine hydrochloride was done on Hypersil BDS C18 (50 mm × 4.6 mm) 3 μm column and 10 mM ammonium acetate in 1000 mL of water was used as buffer. The mobile phase used was in the ratio of buffer-acetonitrile (79:21, v/v). The flow rate was 1.0 mL/min and elution was monitored at 210 nm. The method was validated as per International Conference on Harmonization (ICH) guidelines. LC/MS/MS is able to quantitate up to 0.3 ppm of 2-chloromethyl-3,4-dimethoxy pyridine hydrochloride.