DEVELOPMENT AND EVALUATION OF DIMETHYL SULPHATE AS A GENOTOXIC IMPURITY IN SALBUTAMOL SULPHATE DRUG SUBSTANCE BY USING HPLC

Vinayak T. Vele, Mayur Nibde, Vishal Telvekar, Sushil Singh, Shivaji Kadam, Rupesh Kelaskar, Mohan A Chandavarkar

Abstract


A simple and accurate pre-column derivatization method was developed for the determination of Dimethyl sulphate (DMS)
in the Salbutamol sulphate bulk drug. Alkylation of 2-MercaptoPyridine with Dimethyl sulphate gives corresponding 2-
(Methylthio) Pyridine which is analyzed by reverse phase liquid chromatographic method by using UV detector. Chromatographic separation
between Dimethyl sulphate and Salbutamol sulphate was achieved using a C18 column using a mobile phase containing buffer and acetonitrile in
gradient mode. The resolution between the between Dimethyl sulphate and Salbutamol sulphate was found to be more than 5.0. The limit of detection
(LOD) and limit of quantication (LOQ) of the Dimethyl sulphate was 0.231 and 0.463 μg mL-1, respectively, for 20 μL injection volume. The
percentage recoveries of the Dimethyl sulphate ranged from 94.4 to 98.1 in the samples of Salbutamol sulphate. The developed method was validated
as per International Conference on Harmonization guidelines in terms of specicity, limit of detection, limit of quantication, precision, linearity,
accuracy and ruggedness.


Keywords


Development, Validation, Salbutamol Sulphate, Dimethyl Sulphate, 2-(Methylthio) Pyridine, Derivative, HPLC

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