Stability Indicating RP-HPLC Method for the Determination of Dronedarone Hydrochloride and Its Potential Process-Related Impurities in Bulk Drug and Pharmaceutical Dosage Form

Abstract

Simple, sensitive and accurate stability indicating analytical method for dronedarone has been developed and validated using RP-HPLC technique. Developed method is used to evaluate the assay and related substances of dronedarone drug substance and tablets (Multaq ® ). The drug substance was subjected to the stress conditions such as hydrolysis (acid and base), oxidation, photolysis and thermal degradation as per International Conference on Harmonization (ICH) prescribed stress conditions to show the stability-indicating the nature of the method. Significant degradation was observed during acid and base hydrolysis, and peroxide degradation. The major degredants were identified by LC-MS, FTIR and 1 H NMR spectral analysis. The chromatographic conditions were optimized using an impurity-spiked solution and the samples generated from forced degradation studies. In the developed HPLC method, the resolution between dronedarone, process-related impurities, (namely Imp-1, Imp-2, Imp-3, Imp-4, Imp-5, Imp-6, Imp-7, Imp-8, Imp-9, Imp-10 and Imp-11) and degradation products were found to be greater than 1.5. The eleven potential process related impurities were separated on an Ascentis ® Express C18 column (4.6 × 10 cm i.d., particle size 2.7 µm) at a flow rate of 1.2 mL·min -1 . The LC method employed a linear gradient elution and the detection wavelength at 220 nm. The chromatographic behavior of all the impurities was examined under variable compositions of different solvents, temperatures and pH values.

Stability Indicating RP-HPLC Assay Method for Estimation of Dronedarone Hydrochloride in Tablet

“…The RRT of degradant in alkaline, neutral and peroxide condition matches with impurity-4 while a second degradant was observed in the chromatogram of peroxide stress sample with RRT of 1.16 matches with imp-6 (Landge et al, 2013).…”

“…The sample recovery in a formulation was in good agreement with their respective label claims and that suggested non-interference of formulation excipients in the estimation. The cited literature (Landge et al, 2013) did not report any degradation in alkaline and neutral conditions and moreover the stress conditions applied were milder, even though the degradation was seen with appearance of resolved peaks. Hence the drug can be analyzed in presence of its degradation product indicates that the proposed method is stability indicating.…”

“…A survey of pertinent literature indicates that HPTLC (Dabhi et al, 2012), HPLC (Bhatt et al, 2013;Chhabra and Banerjee, 2013;Tondepu et al, 2012;Patel and Akhtar, 2012;Patel and Choudhury, 2012;Bolderman et al, 2009;Landge et al, 2013), RP-UPLC (Molleti et al, 2013) and Spectrophotometric (Pravalika et al, 2013) methods have been reported on quantification of dronedarone in pharmaceutical dosage forms and in biological samples. The present research work represents development of validated stability indicating P-HPLC method using milder stress conditions and study of degradation kinetics.…”

Innovative methodologies for identification and qualification of Impurities: An overview of the latest trends on impurity profiling

“…The LC method used a linear elution of gradients and a wavelength of detection of 220 nm. Various solvents, temperatures and pH levels were analysed for chromatographic behaviour of the considerable amount of contamination (Landge et al, 2013).…”

Atomic Absorption Spectrophotometer – A Versatile Tool for the Estimation of Nickel Content in Dronedarone

“…It is a new active substance, and there is no official pharmacopoeial procedure available [6]. Literature overviews confess that drug was estimated by different analytical strategies such as spectrophotometric [7], highperformance liquid chromatography [8][9][10][11][12][13][14][15][16][17], and liquid chromatography mass spectrometry [18,19] in bulk drugs and formulation of dronedarone. From the review, it was found that there were no reported methods for the estimation of elemental impurity, i.e., nickel in dronedarone.…”