Stability Indicating RP-HPLC Method for Quantification of Impurities in Valsartan and Hydrochlorothiazide FDC Tablet Dosage Form

Hari Kishan Reddy Ganthi,Woo Hyong Cho,Young Jun Park,So Jin Park,Raveendra Reddy P

doi:10.4236/ajac.2016.711072

Abstract

A stability-indicating RP-HPLC method has been developed and validated for simultaneous determination of Valsartan & Hydrochlorothiazide and their impurities in FDC (Fixed Dose Combination) tablet dosage form. The method was developed using L1 column (250 × 4.6 mm; 5 μm) with gradient elution using the mobile phase consisting of solvent-A (0.1% Ortho phosphoric acid) and solvent-B (100% Acetonitrile); the gradient program (Tmin/%B) was set as 0/10, 5/10, 20/60, 40/60, 41/10 and 50/10. The eluted compounds were monitored at 265 nm. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantitation, accuracy, precision and robustness. The influence of Acid, Alkaline, Oxidative, Photolytic, Thermal and Humidity stress conditions, on drug product was studied. The limit of quantification results of Valsartan, Hydrochlorothiazide and their impurities are, VAL: 0.303 μg/mL, HCTZ: 0.019 μg/mL, VAL RC-B: 0.085 μg/mL, VAL RC-C: 0.327 μg/mL, HCT RC-A: 0.017 μg/mL, CTZ: 0.080 μg/mL and 5-Chloro HCT: 0.047 μg/mL. The proposed method is suitable for the estimation of Valsartan & Hydrochlorothiazide impurities in tablets dosage form.

Highlights

Valsartan & Hydrochlorothiazide are available with the brand name of “Diovan HCTZ” in the form of immediate-release tablets with the dosage strengths VAL/HCTZ: 80
The main target of the chromatographic method is to get the separation of impurities namely HCTZ-1, HCTZ-2, HCTZ-3 and HCTZ-4 of HCTZ & VAL-1 and VAL-2 of VAL and the degradation products generated during stress studies from the analyte peaks along with the actives
A blended solution containing VAL impurities are spiked at 0.2% with respect to VAL concentration of 1600 μg∙mL−1 and HCTZ impurities are spiked at 1.0% and 0.5% with respect to HCTZ concentration of 250 μg∙mL−1 was prepared in diluent and used for the method’s development

Summary

Introduction

Valsartan & Hydrochlorothiazide are available with the brand name of “Diovan HCTZ” in the form of immediate-release tablets with the dosage strengths VAL/HCTZ: 80. Diovan HCTZ is a combination of valsartan, an orally active, specific angiotensin II receptor blocker (ARB) acting on the AT1 receptor subtype, and hydrochlorothiazide, a diuretic [1]. Valsartan (VAL), a nonpeptide molecule, is chemically described as N-(1-oxopentyl)-N[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-L-Valine. Its empirical formula is C24H29N5O3 and molecular weight is 435.5 gms/mol. It is soluble in ethanol and methanol and slightly soluble in water [1]

Objectives

Methods

Results