Development of headspace method for analysis of organic volatile impurities and other residual solvents in drug

Abstract

A headspace technique was developed for the determination of organic volatile impurities and other residual solvents i.e., methylene chloride 1 chloroform 1 benzene, trichloroethylene and 1,4 dioxane in drug samples. The various factors having the effect on sensitivity and percent recovery were studied. The temperature of 70 °c, equilibration time of 40 minutes, the liquid to gas phase volume ratio of 5:5 in 10 mL vial for headspace, 1.00 mL of injection volume, and salting out with 1.00 g. of anhydrous sodium sulfate were chosen as the optimal headspace analysis condition for the analysis of the organic volatile impurities and other residual solvents in drug. The method detection limit of this technique is in the range of 0.2 ppb to 0.2 ppm for all studied compound (except 12.41 ppm for 1,4-dioxane). The accuracy of this technique was also studied and the percent errors are in the range of 0.42 - 5.06 % at the ppm level of concentration. Moreover 1 the developed technique was also applied to analyse fifteen drug samples from thirteen companies. Chromatrographic and mass spectral analysis detected methylene chloride in the concentration of 38.10 - 202.10 µg/g and chloroform in the concentration of 957.10 ng/g. Other volatile solvents found were i.e., cyclohexane, methylamine, pentanone, ethanol, tetrachloroethylene and carbondisulfide