Validated HPLC Method for Determinition of 5-Amino- 2-Methyl Benzoic Acid in Canagliflozin Drug Substances

Abstract

A sensitive, cost-effective, reproducible HPLC method was developed and validate for the quantitative determination of genotoxic impurity 5-amino-2-methyl benzoic acid present in canagliflozin drug substance by applying the concept of threshold of toxicological concern, a limit of 5.0µg/g was calculated based on the maximum daily dose of the drug substance. The impurity was separated on X-terra MS C18, 250 mm x 4.6mm, 5µm analytical column with a mobile phase consisting of the 0.1 % Orthophosphoric acid and methanol with the gradient program at a flow rate 1.0mL/min. The effluent was monitored by UV detection at 228 nm with column temperature maintained at 35 °C and the injection volume 30μL. Validation activity was planned and completed based on the ICH guideline. The LOD and LOQ value were found to be 0.52µg/g and 1.51 µg/g and accuracy results were well in the range 97.99 to 103.46 %. The linearity curve showed the correlation coefficient of 0.9996 and method very sensitive.

Evaluation, Method Development, and Validation for Content Determination of Potential Genotoxic Impurities (PGIs) at the TTC Level in Telmisartan API

“…The quantitative determination of Telmisartan and its related impurities (see Figure ) is well known in the literature. − One liquid chromatography with tandem mass spectrometry (LC/MS/MS) method to ascertain the potentially genotoxic 2-methyl-6-nitro aniline at very low levels in Telmisartan and one high-performance liquid chromatography (HPLC) method for determination of N -methyl- o -phenylenediamine dihydrochloride in Telmisartan drug substances have recently been reported in the literature. , …”

“…18−22 One liquid chromatography with tandem mass spectrometry (LC/MS/MS) method to ascertain the potentially genotoxic 2-methyl-6-nitro aniline at very low levels in Telmisartan and one high-performance liquid chromatography (HPLC) method for determination of N-methyl-ophenylenediamine dihydrochloride in Telmisartan drug substances have recently been reported in the literature. 23,24 Apart from this, there are no previous reports available for the evaluation and analysis of genotoxic impurities of Telmisartan.…”