Development and Validation of A Stability-Indicating Liquid Chromatographic Method for Determination of Valsartan and Hydrochlorthiazide Using Quality by Design

Abstract

The present paper involves the analytical quality by design (AQbD)-based development of a simple, rapid, accurate and precise stability-indicating method for the estimation of valsartan and hydrochlorothiazide. Optimized mobile phase (v/v/v) was water (containing 0.25 ml/L triethylamine), methanol and acetonitrile (50:38:37, pH adjusted to 3.0±0.1). Chromatographic separation was achieved on Hypersil ® -Gold C 18 (150 x 4.6 mm, 5 µm, Thermo Fisher Scientific, USA), column at 25 ± 2 °C. The method was validated as per the "International Conference on Harmonisation" (ICH) guidelines. Chromatographic run time was 10.0 minutes. The linearity range for valsartan and hydrochlorothiazide were 1.25-64.00 µg/ml and 0.195-10.00 µg/ml respectively. The limits of detection (LOD) for valsartan and hydrochlorothiazide were 0.253 and 0.0226 µg/ml while the limits of quantitations (LOQ) were 0.767 and 0.068 µg/ml respectively, using 10µl sample. Stability studies indicate that the degradation of valsartan was higher during oxidative stress than other stress conditions. keywords: Valsartan, hydrochlorothiazide, Central Composite Design, Design of experiments (DoE), Analytical Quality by Design (AQbD), Response surface methodology (RSM), HPLC.

Kinetics and Characterization of Degradation Products of Dihydralazine and Hydrochlorothiazide in Binary Mixture by HPLC-UV, LC-DAD and LC–MS Methods

“…According to the cited works, the highest degradation of hydrochlorothiazide occurred in methanol (53.56%) [ 25 ], 1 M NaOH (69.60%) and 1 M HCl (81.70%) [ 21 ]. In other works, degradation in acidic medium ranged from 0.4 to 17.86% while in alkaline medium from 0.15 to 36.82% [ 19 , 20 , 22 , 25 , 28 , 30 – 32 ]. Hydrochlorothiazide was shown to be stable in the buffer of pH 2.0 and less stable at pH 9.0, where 9.07% of the drug degraded [ 23 ].…”

“…They were carried out in a solid state [ 20 , 22 , 24 , 28 , 31 ] and less frequently in solutions [ 25 , 29 , 30 ]. Stability of hydrochlorothiazide was studied in 1M HCl [ 19 – 22 , 25 , 30 – 32 ], 5 M HCl [ 28 ], 1 M NaOH [ 19 – 22 , 25 , 27 , 31 – 37 ], 5 M NaOH [ 28 ], buffers [ 23 ] and methanol [ 19 , 25 ]. One study on degradation of hydrochlorothiazide by LC/MS method was reported in the literature [ 27 ].…”

Design of Experiment Approach for Method Development and Validation of Bilastine in Pure and Pharmaceutical Dosage form using RP-UFLC

“…In this study, we have used the design of experiments to run a few trials and obtain the optimum conditions to develop the method, validate the same for the drug bilastine in its pure and dosage form using high performance liquid chromatography. Many papers have published the use of such software's [1][2][3][4] . The method development and validation of the drug methotrexate using high performance liquid chromatography (HPLC) was established with the aid of design of experiments 5 .…”