Method development and validation of new drug combinations using advance analytical techniques

Abstract

The single/combine Fixed dosage forms like, OLM, CHLR and CIL tablets, BEN and MET ER tablets, Selexipag are used to treat hypertension. newlineIt is crucial to develop in-vitro drug release method for OLM, CHLR and CIL tablets in single analysis. The objective of the study was to develop drug release method which was optimized based on BCS solubility, media optimization trials and surfactant concentration. newlineGradient reverse phase short run-time HPLC method (LC-MS compitable) was developed to separate OL and OLM Imp. A, CHLR Imp. A and un-known impurities for OLM, CHLR and CIL drug combinations. All thre three known impurities are well separated from OLM, CHLR and CIL peaks. Force degradation study was performed to check degradation pathway. newlineStability indicating related impurities RP-UPLC (LC-MS compatible) method was developed to separate MET Imp. B/D, BEN Imp. 2 and un-known impurities for MET and BEN drug combinations. All the three known impurities are well separated from MET and BEN peaks. Force degradation study was performed to check degradation pathway. newlineIt is very critical to develop in-vitro drug release method for MET (BCS Class-I with ER formulation) and BEN (BCS Class-II, low soluble) tablets in single analysis. The objective of the study was to develop drug release (MET with 1-, 4-, 8- and 20-hours time points) and BEN by using single method which was optimized based on BCS solubility, media optimization trials and optimization of surfactant concentration. newlineNew stability indicating related impurities LC-MS method was developed to separate SEL from SEL Acid, SEL Methyl ester and SEL Imp. A as well as un-known impurities. MRM is the most common method for quantification of analytes by LC-MS/MS have been evaluated for SEL and its known impurities. In MRM, ions are selected from first Quadrupole and further fragmented in collision cell. All the three known impurities are separated from M/Z ratio. Force degradation study performed to check degradation pathway. newlineFurther all the methods have been validated as per.