VALIDATED HPLC METHOD FOR DETERMINITION OF N-METHYL-OPHENYLENEDIAMINE DIHYDROCHLORIDE IN TELMISARTAN DRUG SUBSTANCES

Ritesh Kumar Srivastava* and S. Senthil Kumar

ABSTRACT

A reproducible RP-HPLC method was developed and validated with the aim of quantifying the levels of genotoxic impurity in telmisartan drug substances. A limit level concentration of 18.75 μg/g for N-methyl-Ophenylenediamine dihydrochloride was calculated by applying the concept of threshold of toxicological concern. The impurity was separated on Kromasil C18 150 x 4.6 mm, 5 μm analytical column with a mobile phase consisting of the buffer pH 3.0 and acetonitrile by using the gradient program at a flow rate 1.0 mL/min. The effluent was monitored by UV detection at 230 nm with column temperature maintained at 30 °C and the injection volume 20μL. The developed method was validated as per ICH guidelines in terms of specificity, limit of detection, limit of quantification, linearity, precision, accuracy and robustness. The LOD and LOQ value were found to be 2.53 μg/g and 7.52 μg/g and accuracy results were well in the range 90.68 to 110.21 %. The linearity curve showed the correlation coefficient of 0.9998 and method very sensitive. The validated method was applied for identification and quantification of impurity in different batches of the API.

Keywords: RP-HPLC, API, CH guidelines, Impurity, TTC, Validation.