Spectrodensitometric Determination of Certain Pharmaceutical Binary Mixtures Containing Angiotensin Converting Enzyme Inhibitors and Hydrochlorothiazide

Research Article

Austin J Anal Pharm Chem. 2016; 3(2): 1067.

Spectrodensitometric Determination of Certain Pharmaceutical Binary Mixtures Containing Angiotensin Converting Enzyme Inhibitors and Hydrochlorothiazide

Mohamed HA1, Khashaba PY1 and Shahin RY2*

1Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Assiut University, 71526 Assiut, Egypt

2Drug Research Center, Assiut University, 71526 Assiut, Egypt

*Corresponding author: Reem Y. Shahin, Drug Research Center, Assiut University, 71526 Assiut, Egypt

Received: June 23, 2016; Accepted: July 18, 2016; Published: July 20, 2016

Abstract

A validated HPTLC method was developed for the simultaneous determination of three angiotensin converting enzyme inhibitors namely enalapril maleate, moexipril HCl, and ramipril HCl, in binary mixture with hydrochlorothiazide. Separation was achieved on silica gel 60 F254 HPTLC plates using mobile phases: as chloroform- ethylacetate- methanol (10:1:5 v/v/v) for enalapril maleate : hydrochlorothiazide (Rf: 0.27: 0.67); ethylacetate-chloroformglacial acetic acid (8:2:0.2 v/v/v) for moexipril HCl: hydrochlorothiazide (Rf : 0.15 : 0.45); and benzene- methanol- glacial acetic acid (8:2.5:0.4 v/v/v) for ramipril HCl : hydrochlorothiazide (Rf: 0.50: 0.65). Measurements were recorded with UV densitometry at 223, 216 and 210 nm for the simultaneous determination of the three binary mixtures of enalapril maleate, moexipril HCl, and ramipril HCl each with hydrochlorothiazide, respectively. The proposed method was validated according to ICH and was found to be specific, accurate, precise and robust. It was also successfully applied to the simultaneous determination of EN; RAM each with HCT in tablet dosage form without interference from common excipients.

Keywords: Angiotensin converting enzyme; Hydrochlorothiazide; HPTLC; Binary mixtures

Introduction

High performance thin layer chromatography (HPTLC) is one of the most widely used techniques for the separation and identification of drugs. It is an ideal technique because of its simplicity, low cost, selectivity, and ability to be performed without a remote area (away from a laboratory) with limited volume of solvents. Angiotensin converting enzyme inhibitors (ACEIs) are commonly prescribed with the diuretic drug hydrochlorothiazide (HCT) in binary mixture for the treatment of essential hypertension, stable chronic heart failure, myocardial infarction and diabetic nephropathy. They are sometimes administered separately and commonly administered as binary mixture form in tablets. Enalapril (EN) (2S)-1-[(2S)-2-{[(2S)-1- ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]pyrrolidine-2- carboxylic acid, moexipril (MOX)(3S)-2-[(2S)-2-{[(2S)-1-ethoxy-1- oxo-4-phenylbutan-2-yl]amino}propanoyl]-6,7-dimethoxy-1,2,3,4- tetrahydroisoquinoline-3-carboxylic acid and ramipril (RAM) (2S,3aS,6aS)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl] amino}propanoyl]-octahydrocyclopenta pyrrole-2-carboxylic acid (III), belong to the class of dicarboxylate containing group of ACEIs. Figure 1 shows the chemical structure of the studied drugs. The reported methods for the determination of the studied binary mixtures include ultraviolet (UV) derivative spectrophotometric methods [1-5], high performance liquid chromatography (HPLC) methods [6-10]. For our knowledge only one TLC method [11] was reported for simultaneous determination of EN-HCT, no methods were reported for the determination of binary mixtures of RAM or MOX with HCT by TLC. So the aim of work in this part depends on HPTLC separation of three binary mixtures: EN-HCT, RAMHCT, and MOX-HCT followed by simultaneous determination at their isoabsorbtive points in the range of 210-223 nm. Dosage forms containing ACEIs (EN or RAM) with HCT are available in the Egyptian, European and American markets, while -till now- MOX-HCT tablets aren’t available in the Egyptian market, but are available in the European and American markets such as Uritec® tablets. Therefore synthetic mixture of MOX-HCT was prepared in our laboratory and subjected to the proposed spectrodensitometric method. The proposed method was applied successfully for the assay of the studied binary mixtures in their pharmaceutical dosage forms.