Analytical Method Development for Selected Cardiovascular Drugs and Its Application for Impurity Profiling Degradation and In Vitro Drug Drug Interaction studies

Abstract

In the current research work UV Spectroscopy and chromatographic methods were developed for the four drugs namely apixaban, rivaroxaban, ibutilide fumarate and dofetilide. These methods provide the availability of the simple way of analysis with strategic and segmented working procedure adopted. Each of the analytical method is economical, time saving, and easily adaptive. The UV Spectroscopic method for apixaban, ibutilide fumarate and dofetilide is advantageous as there is minimum steps involved the sample preparation, time of analysis and procedure. The HPTLC method developed and validated for the four drugs offers a very selective, sensitive and speedy analysis of the samples. Sensitivity of the method is proven with the results obtained in the nanogram level for the drugs. Among all the three methods, the HPTLC method is highly sensitive. The HPLC method was found to be highly selective that they effectively quantified the selected drugs without any interference of matrix (excipients), impurity or degradants. The isocratic mode of operation is efficient and advantageous with only aqueous andorganic solvents used in the mobile phase without any buffer system. There is no reported pharmacokinetics data available till date for ibutilide fumarate. The interaction studies developed and validated is a model for the metabolic pathway of ibutilide fumarate as the rat liver microsomes consists of cytochrome 450 enzymes. The steady state concentration level of ibutilide fumarate when present with verapamil till four hours depicts the interference of verapamil in the metabolic pathway of ibutilide. The results implify a concern on the co-administration of ibutilide fumarate and verapamil. Hence the co administration of ibutilide fumarate and verapamil has to be given serious consideration. The analytical methods developed and validated can be applied for the routine analysis of the drug substance in the bulk and dosage forms. The applications of the methods adopted signifies the stability of the drugs under the degradation conditions.