Determination of Valbenazine related substances by liquid chromatography method complying with the current regulatory guidelines. Method robustness evaluation by Design of Experiments software

Abstract

AbstractA simple, specific, rapid, sensitive reversed‐phase high‐performance liquid chromatography method was developed and validated for the determination of Valbenazine, impurities, and its degradation products. The proposed high‐performance liquid chromatography method showed optimum separation in 60 min using potassium dihydrogen phosphate buffer and ACN in the ratio of 90:10 (V/V) as mobile phase‐A whereas ACN and methanol in the ratio of 60:40 (V/V) as mobile phase‐B. YMC‐Pack ODS‐AQ (150 × 4.6 mm, 3.0 μm), column used along with security guard cartridge C18, (4.0 × 3.0 mm) at 1.1 ml/min flow. The injection volume was 10 μl and detection was carried out at 285 nm. The drug was degraded under different stress conditions and the method was validated as per International Conference on Harmonization guidelines on the basis of accuracy, precision, linearity, and robustness. A degradation study indicates that Valbenazine is prone to oxidative degradation. The method was linear over the concentration range of limit of quantitation to 200% for impurities and drug substances. The method was found robust and was studied by the design of experiments. The proposed method is applicable for the determination of the stability of Valibenazine and was successfully used in the quality control of bulk drug manufacturing and pharmaceuticals.