Bioanalytical HPLC method development for simultaneous determination of valsartan and co-administered clopidogrel bisulfate and fenofibrate in stroke prevention in raw materials, spiked human plasma and tablets

Gamal H Ragab,Eman A Bahgat

doi:10.2478/nbec-2018-0015

Abstract

Abstract This study reports about simple, robust and reproducible method for simultaneous bioanalytical determination of Valsartan (VAL) and co-administered Clopidogrel bisulfate (CGB) and Fenofibrate (FEN) in raw materials, spiked human plasma and tablets using isocratic RP-HPLC method. The chromatographic separation is carried out using isocratic binary mobile phase consisting of 80 mM phosphate buffer pH 3: Acetonitrile (30: 70 %; v/v) at the flow rate of 1.1 mL/min and 33 °C. A Diode array detector at wavelength 214 nm was used. Retention times for VAL, CGB and FEN were 3.1, 5.1 and 6.4 min, respectively. The calibration curves obtained were linear over the concentration ranges of 2.5 - 100 μg/mL for both VAL and CGB and 5 -100 μg/mL for FEN. The mean extraction recoveries of VAL, CGB and FEN from spiked plasma were 75.38±1.34 %, 89.91±2.17 % and 96.92±6.02 %, respectively. The limits of detection and quantification were 0.86, 0.67, 1.11 μg/mL and 2.60, 2.03, 3.36 μg/mL for VAL, CGB and FEN, respectively. The method was applied to the analysis of these drugs in spiked human plasma and in tablets as they are commonly used as a combination for prevention of stroke. Results obtained show good accuracy, precision and acceptable recoveries from plasma samples.

Highlights

Valsartan is an angiotensin-II receptor antagonist, used in treatment of hypertension
Valsartan have been determined by using RP-HPLC methods in combination with hydrochlorothiazide in tablets (Tian et al 2008) and with amlodipine and hydrochlorothiazide in tablets and spiked human plasma (El-Gizawy et al 2012)
We introduce a simple, robust and precise HPLC method for simultaneous determination of a very effective combination of drugs that are used for secondary prevention of stroke which is Valsartan as antihypertensive, Clopidogrel bisulfate as antiplatelet and Fenofibrate as lipid modifier

Summary

Introduction

Valsartan is an angiotensin-II receptor antagonist, used in treatment of hypertension. We introduce a simple, robust and precise HPLC method for simultaneous determination of a very effective combination of drugs that are used for secondary prevention of stroke which is Valsartan as antihypertensive, Clopidogrel bisulfate as antiplatelet and Fenofibrate as lipid modifier. The developed method has been created to determine these drug combinations in both spiked human plasma and in tablets dosage form. Analysis process was carried out at ambient temperature using Agilent Thermo Hypersil (250 mm × 4.6 mm I.D, 5 μm particle size column) and the mobile phase was an isocratic mixture of acetonitrile and 80mM potassium dihydrogen orthophosphate buffer (pH= 3±0.2 adjusted using orthophosphoric acid) in a ratio of (70 : 30; v/v). The procedures were completed as mentioned above and the concentrations of the three drugs were obtained from the computed regression equations

Method validation

Method development

Conclusions