Genotoxicity

A sensitive and rapid HPLC method was developed and validated for the determination of potential genotoxic impurities i.e (Bromomethyl)biphenyl methyl ester and (Dibromomethyl)biphenyl methylester at trace level in Telmisartan drug substance by applying the concept of threshold of toxicological concern (TTC). The HPLC method was developed and optimized on Symmetry Shield RP18, 3.5 m (150mm × 4.6mm) column with oven temperature maintaining at 40°C and 0.02M Phosphate buffer pH 2.5 was chosen as mobile phase A and mixture of acetonitrile and Phosphate buffer (55:45) was selected as mobile phase B in gradient reverse phase mode in isocratic mode of composition. Chromatographic parameters i.e flow rate: 1.0 ml/min, wavelength detection: 205 nm, injection volume: 20µl and run time: 25 min were applied in this methodology.  Based on validation data, the method is found to be specific, sensitive, accurate and precise. The established limits of Limit of detection and Limit of quantification for subjected impurities are found to be 2.4 µg/g and 4.7 µg/g respectively for each impurity. The recovery at LOQ level obtained was 98.2% for (Bromomethyl) biphenyl methyl ester and 99.2% for (Dibromomethyl) biphenyl methyl ester. This method can be used as good quality control tool for quantization of these impurities at low level. The experimental results are discussed in detail in this research paper.

A sensitive and rapid HPLC method developed and validated for the determination of potential genotoxic impurity namely m-aminobenzoic acid at trace level in Ertapenem monosodium by applying the concept of threshold of toxicological concern (TTC). The HPLC method was developed and optimized on Inertsil ODS-3V, 250 mm × 4.6 mm, 5mm column with oven temperature maintaining at 40°C. 0.02M Sodium Phosphate buffer pH 2.5 was chosen as mobile phase A and methanol was selected as mobile phase B in gradient reverse phase mode. Chromatographic parameters i.e flow rate: 1.0 ml/min, wavelength detection: 220 nm, injection volume: 10µl and run time: 20 min were applied in this methodology. Based on validation data, the method is found to be specific, sensitive, accurate and precise. The established limits of Limit of detection and Limit of quantification for this impurity are found to be 3.9 µg/g and 11.9 µg/g respectively.  The average recovery obtained was 99.8% at four levels in twelve determinations for m-aminobenzoic acid in Ertapenem monosodium drug substance. This method can be used as good quality control tool for quantization of m-aminobenzoic acid at low level. The experimental results are discussed in detail in this research paper.