Simultaneous Determination of 2-Chloro Methyl Propionate, 1,4-Di-Bromo Butane and Para Anisic Aldehyde in Mebeverine Hydrochloride Api by Gas Chromatography-Mass Spectrometric With Selected-Ion-Monitoring Mode

Abstract

Objective: To develop an accurate, precise and linear gas chromatography-mass spectrometric (GC-MS) selected-ion-monitoring (SIM) method for quantitative estimation of 2-chloro methyl propionate (2-CMP), 1,4-dibromo butane and para anisic aldehyde (PAA) as an genotoxic impurities in mebeverine HCl API (MEB) at ppm level and validated as per International Council of Harmonization (ICH) guidelines. Methods:This method used in SIM mode mass selective detection was developed and validated for the trace level analysis of three impurities. All these three impurities are simultaneously determined by a GC-MS method using VF-624 Capillary column (60 m×0.32 mm×1.80 µm) with Helium as carrier gas and a flow rate of 2.0 mL/minutes. Chromatographic separation of 2-CMP, 1,4-DBB, and PAA was achieved in 7.91, 13.69, 18.45 minutes and m/z values were 63, 55, 135 on SIM mode. Results:The method was linear for 2-CMP, 1,4-DBB and PAA in mebeverine HCl 1.90 µg/ml to 7.5 µg/ml, respectively. The coefficient of correlation (r 2 ) for the 2-CMP, 1,4-DBB and PAA was better than 0.999. The limit of detection obtained was 0.28, 0.35, 0.22 µg/ml and the limit of quantification (LOQ) obtained was 0.85, 1.06, 0.66 µg/ml. The method was fully validated, complying Food and Drug Administration, ICH and European Medicines Agency guidelines. Furthermore, verified precision, accuracy, LOQ precision, LOQ accuracy, ruggedness, and robustness. Conclusion:The proposed method is specific, accurate, precise, linear, rugged and robust for the determination of the three genotoxic impurities in API of mebeverine HCl, and hence, is of wide applicability in pharmaceutical industries.