Simultaneous determination of aliskiren and hydrochlorothiazide from their pharmaceutical preparations using a validated stability‐indicating MEKC method

Abstract

A stability-indicating MEKC method was developed and validated for the simultaneous determination of aliskiren (ALI) and hydrochlorothiazide (HCTZ) in pharmaceutical formulations using ranitidine as an internal standard (IS). Optimal conditions for the separation of ALI, HCTZ and its major impurity chlorothiazide (CTZ), IS and degradation products were investigated. The method employed 47 mM Tris buffer and 47 mM anionic detergent SDS solution at pH 10.2 as the background electrolyte. MEKC method was performed on a fused-silica capillary (40 cm) at 28°C. Applied voltage was 26 kV (positive polarity) and photodiode array (PDA) detector was set at 217 nm. The method was validated in accordance with the ICH requirements. The method was linear over the concentration range of 5-100 and 60-1200 μg/mL for HCTZ and ALI, respectively (r(2) >0.9997). The stability-indicating capability of the method was established by enforced degradation studies combined with peak purity assessment using the PDA detection. Precision and accuracy evaluated by RSD were lower than 2%. The method proved to be robust by a fractional factorial design evaluation. The proposed MEKC method was successfully applied for the quantitative analysis of ALI and HCTZ both individually and in a combined dosage tablet formulation to support the quality control.

Stress degradation studies on aliskiren and the development of a sensitive stability-indicating MEKC method

“…The LOQ found by developed MEKC method is more sensitive than the published LC and MEKC methods [9,12]. The proposed method can be useful for the determination of ALI without prior separation of the excipients of the formulation, with advantages of small sample volumes, without consumption of organic solvents and short analysis time.…”

“…These conditions were based on published paper with some modifications to adequate to the new MEKC method [12]. A sample solution prepared in 2 M hydrochloric acid (HCl) was used for acidic hydrolysis, and a sample solution in 2 M sodium hydroxide (NaOH) for basic hydrolysis evaluation.…”

“…A simultaneous determination of ALI and hydrochlorothiazide by LC was developed and validated using a monolithic column [11]. A MEKC method was also validated for simultaneous analyses of ALI and hydrochlorothiazide, but this method has a migration time around 4.0 min and was linear over the concentration range of 60-1200 µg mL −1 [12]. The present method showed a limit of quantitation (LOQ) of 4.38 μg mL −1 with linearity in the range of 5-150 μg mL −1 , and migration time of 3.55 min.…”

HPTLC Method for Simultaneous Estimation of Aliskiren, Amlodipine, and Hydrochlorothiazide in Synthetic Mixture Using Quality by Design Approach

“…A few methods had been reported for ALI and its combinations with AMD, VAL and HCT [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] (10cm x 10cm). TLC Silica gel 60 F 254 precoated plates with layer thickness 0.2mm and manually cut dimensions 10 cm x 10 cm (E-Merck-KgaA) were used.…”

Application of Chromatographic and Spectrophotometric Methods for The Analysis of Aliskiren and Hydrochlorothiazide Antihypertensive Combination.

“…Moreover, several analytical methods have been described in literature for the determination of ALK and HCT in pharmaceutical and biological samples. These methods include HPLC [20,21] and MEKC [22]. In the present work, three different, rapid, sensitive and cost-effective methods, namely HPLC, simultaneous equation and dual wavelength spectrphotometry, were described for the simultaneous determination of ALK and HCT in binary mixture and in pharmaceutical dosage form with subsequent validation of all the proposed methods.…”