Static headspace gas chromatographic method for the determination of residual solvents in cephalosporins

Abstract

The pharmaceutical industry is facing a daunting challenge in the control of impurities. According to the GMP, measuring residual solvents is an integral part of impurity profile assessment for pharmaceutical products and is mandatory for the release testing of all active pharmaceutical ingredients or drug products according to regulatory authorities' requirements. Cephalosporins were surveyed for solvents being used in their synthetic processes, followed by establishment of a general method for the determination of these solvents. A sensitive static headspace gas chromatography (HSGC) with flame ionization detector (FID) protocol was successfully developed and validated for the determination of residual solvents commonly used in cephalosporin syntheses. The headspace and chromatographic parameters, such as split ratio, flow rate and oven programmed temperature, were optimized to enhance sensitivity and chromatographic resolution. Dimethyl-acetamide (DMA)–water 1 : 1, v/v mixture as diluent, equilibration temperature of 120 °C for 5 min, programmed temperature in the range of 40–155 °C, helium as carrier gas and a capillary column (6% cyanopropyl-phenyl–94% dimethyl polysiloxane) with 30 m × 0.32 mm id × 1.8 μm film thickness, were used. The proposed method was found to be suitable for the determination of 11 different residual solvents. Validation results indicated method specificity, sensitivity, and accuracy, where recoveries ranged from 98 to 103%. Regarding all analytes r = 0.995–1.000, except for n-hexane and cyclohexane for which r = 0.980 and 0.988, respectively.