A Stability Indicating HPLC Method for Dronedarone in Bulk Drugs and Pharmaceutical Dosage Forms

Abstract

The objective of the current study was to develop a validated, specific and stability-indicating reverse phase HPLC method for the quantitative determination of Dronedarone and its related substances. The determination was done for active pharmaceutical ingredient and its pharmaceutical dosage forms in the presence of degradation products, and its process-related impurities. The drug was subjected to stress conditions of hydrolysis (acid and base), oxidation, photolysis and thermal degradation per International Conference on Harmonization (ICH) prescribed stress conditions to show the stability-indicating power of the method. Significant degradation was observed during acid, oxidative and photo stress studies. In the developed HPLC method, the resolution between Dronedarone and its process-related impurities was found to be greater than 2.0. Regression analysis shows an r value (correlation coefficient) of greater than 0.999 for Dronedarone and it's all the five impurities. The chromatographic separation was achieved on a C8 stationary phase. The method employed a linear gradient elution and the detection wavelength was set at 288 nm. The stress samples were assayed against a qualified reference standard and the mass balance was found to be close to 99.6%. The developed HPLC method was validated with respect to linearity, accuracy, precision and robustness.

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.…”

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

“…A literature survey also revealed that the analytical methods were available for the investigation of pharmacokinetics of dronedarone where the content of dronedarone individually and with its active metabolite de-butyldronedarone in human plasma was studied by liquid chromatography-tandem mass spectrometry [7] and HPLC-UV [8] methods respectively. Stability indicating HPLC method reported [9] for dronedarone bulk drugs samples and pharmaceutical dosage forms has been found to be non-selective at our end. In addition, few other methods for the quantitative determination of dronedarone in pharmaceutical dosage forms have also been reported [10,11].…”

“…The wavelength selected (288 nm) was also found to be not suitable for the determination of dronedarone and specified impurities. Methods [8,9], were also found to be nonspecific for said impurities determination Thus we felt a need for the development of a new chromatographic method that detect and determine all the potential process and degradation related impurities viz., Imp-1 to Imp-11 present in bulk samples of dronedarone hydrochloride and to achieve the separation of all eleven impurities (Figure 1) from the analyte peak. The new method developed in our laboratory showed separation of all the eleven impurities of dronedarone hydrochloride satisfactorily as shown in Figure 5(b).…”

“…provide an indication of the stability-indicating property and specificity of the proposed method [7][8][9][10][11][12]. The stress conditions employed for the degradation study included light (carried out as per ICH Q1B), heat (105˚C), acid hydrolysis (Conc.HCl), base hydrolysis (5 M NaOH), Water hydrolysis (Refluxed for 12 h) and oxidation (5% H 2 O 2 ).…”

Synthesis and characterization of new related substances of the antiarrhythmic drug dronedarone hydrochloride

“…2. They include the synthetic intermediates 3, 5 and 6 and the disulfonamide derivative known as impurity B (7) [9], that is a by product from the sulfonylation step. In addition, debutyldronedarone (8), which is known as the major circulating metabolite after oral administration of Dronedarone, is also included here [10,11].…”