A SIMPLE AND SENSITIVE RP-HPLC METHOD FOR TRACE-LEVEL QUANTIFICATION OF METHYL VINYL KETONE, A POTENTIAL GENOTOXIC IMPURITY, IN DRUG SUBSTANCESAbstract
An HPLC method was developed with the aim of quantifying the levels of Methyl Vinyl Ketone (MVK), a Potential Genotoxic Impurity (PGI), in Ivabradine HCl. A limit level concentration of 0.5 ppm for MVK was calculated by applying the concept of Threshold of Toxicological Concern (TTC). The developed HPLC method employs a Phenyl analytical column (150 mm х 4.6 mm, 3.5 μ), 5-μL injection volume, mobile phase of buffer (pH 2.5)-acetonitrile [gradient elution], a column temperature of 50°C and a flow rate of 1.0 mL/min. The retention time of MVK obtained was approximately 4.0 minutes in a program with run time of 22 minutes. The Limit of Detection was 0.06 ppm and Limit of Quantitation was 0.2 ppm. The method proved to be sensitive, linear, accurate and precise in the specified range (LOQ to 150 % of limit level concentration). The validated method was applied for identification and quantification of MVK in different batches of the API.
Deepali Gangrade * and Jessica D’Souza
Department of Quality Assurance, Vivekanand Education Society’s College of Pharmacy, Chembur(East), Mumbai-400074, Maharashtra, India.
23 July, 2016
27 November, 2016
28 November, 2016
01 February, 2017