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Development of a Highly Sensitive Method for Quantitative Estimation of Dimethyl Sulfate Impurity in Neostigmine Methylsulfate Drug substances by Using GC-MS

Amit Gosar, Amit Joglekar, Tabrez Shaikh, Sandeep Mhatre, Swapnil Patil


A selective and highly sensitive gas chromatography-mass spectrometry (GC-MS) method was developed for the determination of Dimethyl Sulfate (DMS) impurity in Neostigmine Methylsulfate drug substance. The method was validated as per International Council for Harmonisation (ICH) guidelines, for which limit of detection and limit of quantitation obtained were 25.48 ppm and 77.20 ppm, respectively. The regression coefficient found for the linearity study was 0.9986. The recovery of the spiked Dimethyl Sulfate in drug substance obtained was in the range of 84.40% to 88.24% ensured the accuracy of the method The method precision with relative standard deviation (RSD) for repeatability and intermediate precision was less than 5%. The method can be adapted to determine Dimethyl Sulfate in Neostigmine Methylsulfate drug substance (API).

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