DEVELOPMENT AND VALIDATION OF GAS CHROMATOGRAPHY METHOD FOR THE DETERMINATION OF GENOTOXIC IMPURITY, EPICHLOROHYDRIN, IN LINEZOLID DRUG

摘要

A sensitive and robust gas chromatography with a flame ionization detector method was developed for the quantification of epichlorohydrin in the linezolid drug substance and validated using guidelines as mentioned in ICH Q2 (R1). Epichlorohydrin was separated on CP-Volamine stationary phase (length 60 m, diameter 0.32 mm, particle size 5 μ) in linear thermal programming using dichloromethane as a diluent, at a constant flow rate of 2 ml/min. Column oven temperature maintained initiated at 90 oC and raised to temperature 230 oC with run time 25 min. Epichlorohydrin showed linearity from 5.12 ppm to 30 ppm concentration range. The method has satisfactory precision and accuracy. Limit of detection and limit of quantification were found as 2.03 ppm and 5.12 ppm, respectively. The epichlorohydrin peak has been well resolved and its specificity has been demonstrated. The method developed and validated for estimating epichlorohydrin in linezolid drug molecule is easy and simple to adopt in any pharmaceutical laboratory.