Analytical method development and validation for fixed dose combination pharmaceutical products

Abstract

The fixed-dose combination products like AMD, HCTZ and OLM Tablets, ATV and EZB Tablets are used to prevent hypertension. It is critical to separate and quantify individual known and unknown impurities with optimum resolution from each other in a combination product with a single chromatographic method. The objective of this study was to develop and validate high-resolution methods for impurities in fixed-dose combination products AMD, HCTZ and OLM Tablets and ATV and EZB Tablets by using advanced techniques i.e. RP-HPLC and UPLC. By using the gradient reversed-phase high-pressure liquid chromatographic method, a total of 23 known and unknown impurities related to AMD, HCTZ and OLM in combining formulation were separated and quantified in the range of 0.05% of AMD, HCTZ and OLM to 150% of the specification level. In this study, two separate analytical methods RP-HPLC and UPLC have been developed, validated and compare for the simultaneous quantification of ALM, HCTZ and OLM tablets with their impurities. newlineBy using the gradient reversed-phase high-pressure liquid chromatographic method, unknown impurities of ATV and EZB separated. One unknown degradation impurity of ATV was identified. The impurity is enriched by extreme oxidation degradation of ATV and isolated through preparative HPLC. The isolated impurity is characterized by Mass and NMR. An analytical method for impurity profiling was developed and validated in the range of 0.05% to 0.2%. newlineThe proposed methods have a high degree of sensitivity and are capable to provide fast and cost-effective quantitative control of Pharmaceutical formulations.