METHOD DEVELOPMENT AND VALIDATION OF DIMETHYL SULPHATE CONTENT IN ESOMEPRAZOLE MAGNESIUM DRUG SUBSTANCE BY GC-MS

Abstract

Dimethyl sulfate is universally used as an alkylating, sulfating and sulfonating agent in organic synthesis; hence it is one of the probable impurities during the synthesis of the esomeprazole magnesium. As per ICH M7, it is genotoxic and mutagenic, so it needs to be controlled as per the acceptable intake of dimethyl sulfate and daily sample dosage. This method validation can be achieved by the hyphenated technique of gas chromatography with mass spectroscopy, which is used to develop the dimethyl sulfate impurity in esomeprazole magnesium drug substance containing salt. The method is achieved with a DB-1 column with electron impact ionization source in sim mode ion under electronic pneumatic pressure control and deliberate oven ramp programming temperature was used. A dissolved, extracted and auto-injection sample was implemented for sample introduction in a splitless mode. Dichloromethane and 2N NaOH was used as a diluent. The calibration curve showed good linearity over the 1.69 to 8.40 ppm (limit: 5.56 ppm) and its correlation coefficient was >0.999. A limit of detection 0.50 ppm and limit of quantitation 1.69 ppm was achieved when the samples were prepared at 50 mg/mL. While recovery proved to be 106.8 to 113.5%, hence it signified the matrix effect.