DEVELOPMENT AND VALIDATION OF GC-MS METHOD FOR THE TRACE LEVEL DETERMINATION OF STRUCTURALLY ALERT ALKYL HALIDE IMPURITIES IN CILASTATIN SODIUM DRUG SUBSTANCE

A Simple and trace level-sensitive Gas chromatography with mass spectrometer (GCMS) method was developed, optimized and validated for the determination of seven potentially genotoxic impurities which are having structural alerts i.e., 1-Bromo-5-chloropentane (PGI-1), Ethyl-6-chloro-2-oxo hexanoate (PGI-2), Methyl-7-chloro-2-oxo hepta-noate (PGI-3), Ethyl-7-chloro-2-oxo heptanoate (PGI-4), Ethyl-7-bromo-2-oxo heptanoate (PGI-5), Ethyl-8-chloro-2-oxo octanoate (PGI-6), Ethyl-2-acetyl-7-chloro heptanoate (PGI-7) contents in Cilastatin sodium drug substance. The chromatographic separations of seven genotoxic impurities were achieved on ZB-5 MS [5% Polysilarylene, 95% Poly-dimethylsiloxane copolymer capillary column of 30 m length, 0.32 mm internal diameter, film thickness 1.0 µm]. The analytic method has been demonstrated through method validation experiments w.r.t ICH guidelines, like specificity, linearity, Limit of Detection, Limit of Quantification, method precision and accuracy (recovery) parameters with allowable TTC limit. The achieved limit of detection (LOD) values was 3 µg/g. This developed method was found to be linear with correlation coefficient is greater than 0.999. Developmental and validation experiments were discussed in detail in this paper.