Redox Pathways of Aliskiren Based on Experimental and Computational Approach and Its Voltammetric Determination

Deniz Pamuk,İbrahim Hüdai Taşdemir,Abdulilah Ece,Esma Kılıç,Esin Canel

doi:10.5935/0103-5053.20130162

Abstract

Electrochemical behavior of aliskiren (ALS) was studied via experimental electrochemical methods and theoretical calculations performed at B3LYP/6-31+G (d)//AM1. Cyclic voltammetry studies were carried out based on the adsorption-controlled reversible reduction at ca. -1.5 V on hanging mercury drop electrode (HMDE) and irreversible electrochemical oxidation of ALS at ca. 1.0 V on glassy carbon electrode (GCE), vs. Ag/AgCl, KCl (3.0 mol L-1), in Britton-Robinson buffer at pH 10 and 8, respectively. According to computational and experimental findings, ALS is expected to be oxidized irreversibly at benzylic position and reduced reversibly at amide carbonyl groups. Voltammetric methods with and without adsorptive stripping mode were developed and validated for quantification of ALS in different samples. Limits of detection and of quantification for ALS were 6.3 × 10-8 and 2.1 × 10-7 mol L-1 for differential pulse voltammetry on HMDE and 1.2 × 10-8 and 3.9 × 10-8 mol L-1 for square-wave cathodic adsorptive stripping voltammetry. The methods were successfully applied to assay the drug in tablets and human serum with good recoveries, between 91.7 and 102.3%, having relative standard deviation less than 10%.

Highlights

Aliskiren (ALS), chemically known as (2S,4S,5S,7S)5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy7-{[4-methoxy 3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide (Figure 1), is an oral renin inhibitor used in the treatment of hypertension
The electrochemical behavior, diffusion and adsorption properties of ALS were studied on hanging mercury drop electrode (HMDE) on the reduction side and on glassy carbon electrode (GCE) on the oxidation side
Electrochemical characteristics of ALS on HMDE and GCE with the help of ab initio calculations were studied for the first time

Summary

Introduction

Aliskiren (ALS), chemically known as (2S,4S,5S,7S)5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy7-{[4-methoxy 3-(3-methoxypropoxy)phenyl]methyl}-. It can be used in combination with other drugs in the antihypertensive class, as well as alone.[1] Electrochemical studies and their results might be used in the investigation of physical, chemical and redox behaviors of organic-inorganic molecules. Some of these properties and their evaluation are of great importance. To biologically important molecules, especially to drug compounds Electrochemical methods make it possible to evaluate reduction and oxidation characteristics, plausible redox pathways and adsorption-diffusion parameters ofmolecules under investigation.[2,3,4,5,6,7] These parameters are important for distribution, metabolism, pharmacological, toxicological and pharmacokinetic properties of drugs. To the best of our knowledge, up to the present time, there is no electrochemical study dealing with voltammetric determination of ALS in pharmaceutical formulation and biological samples.

Procedure

Computational Methodology

Results and Discussion

Method

Conclusion