Alkyl tosylates or alkyl p-toluene sulfonates are very well known class of genotoxic impurities. As a genotoxic impurity, specified limits for these impurities are very low; hence sensitive analytical techniques are required for analyzing these impurities. Gas chromatographic method with mass spectrometer as detector was developed and validated for evaluating methyl tosylate, Isopropyl tosylate and butyl tosylate in clopidogrel bisulphate API. DB-5MS capillary column of 60 m length, 0.25 mm I.D and film thickness 0.25 m was selected. Ionization technique used was EI and the single Quadruple mass analyzer was used. By performing method validation it was verified that the method is sensitive, precise, accurate and linear. The maximum recommended daily dose of clopidogrel bisulphate is 300 mg. Hence, based on daily dose, evaluation as well as further specification limit is 5 µg/g. Limit of detection is 0.39 µg/g (0.02 µg/ml), 0.57 µg/g (0.03 µg/ml) and 0.16 µg/g (0.01 µg/ml) for methyl tosylate, isopropyl tosylate and butyl tosylate respectively. Similarly, Limit of quantification for methyl tosylate, isopropyl tosylate and butyl tosylate is 1.18 µg/g (0.06 µg/ml), 1.72 µg/g (0.09 µg/ml) and 0.5 µg/g (0.03 µg/ml) respectively. Linearity of all the three impurities is verified from LOQ to 150% of the evaluation level. Accuracy and precision of the method are evaluated. Analysis of commercial batches of Clopidogrel bisulphate is performed for these impurities and is concluded that the method is suitable to be extended for routine analysis.
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