ABSTRACT
A simple, sensitive, precise and accurate stability-indicating ultra-performance liquid chromatography (UPLC) method was developed for the quantitative determination of the purity of the active pharmaceutical ingredient of milnacipran hydrochloride (MCP) and its pharmaceutical dosage form in the presence of its process-related impurities and degradation products. The proposed UPLC method utilizes Acquity UPLC BEH 100 mm, 2.1 mm and 1.7 µm phenyl columns at 27°C with a gradient program of 12.0 min at a flow rate of 0.5 mL/min. The compounds of interest were monitored at 210 nm. The resolution for MCP and 12 (potential byproducts and degradation) impurities was found to be greater than 2.0 for any pair of components. The high correlation coefficients (r(2) >0.9995) indicate clear correlations between the concentrations of investigated compounds and their peak areas. The relative standard deviations obtained for the repeatability and intermediate precision experiments were less than 5.0%. The accuracy of the method was further ascertained by performing recovery studies through spiking experiments. The drug substance was subjected to hydrolytic, oxidative, photolytic and thermal stress conditions, as per the International Conference on Harmonization (ICH). The developed method was validated according to the current ICH guidelines for specificity, limits of detection and quantitation, linearity, accuracy, precision, ruggedness and robustness. The method is also suitable for the assay determination of MCP in pharmaceutical dosage forms.
Subject(s)
Cyclopropanes/analysis , Cyclopropanes/chemistry , Chromatography, Liquid , Drug Stability , Hydrogen-Ion Concentration , Limit of Detection , Linear Models , Mass Spectrometry , Milnacipran , Reproducibility of Results , Tablets/chemistryABSTRACT
A simple, sensitive and reproducible method was developed on ultra-performance liquid chromatography coupled with photodiode array detection for the quantitative determination of dronedarone hydrochloride (DRO) in drug substance and pharmaceutical dosage forms. The method is applicable for the quantification of related substances and assays of drug substances. Chromatographic separation was achieved on Acquity UPLC BEH C8 100 mm, 2.1 mm and 1.7 µm columns, using gradient elution within a short run time of 10.0 min. The eluted compounds were monitored at 288 nm, the flow rate was 0.5 mL/min and the column oven temperature was maintained at 40°C. The resolution of DRO and 11 impurities (potentials and by-products) was greater than 2.0 for all pairs of components. The high correlation coefficient value (>0.9995) indicates the clear correlations between the concentrations of investigated compound and their peak areas within the test ranges. The repeatability and intermediate precision, expressed by the relative standard deviation, were less than 2.5%. The accuracy and validity of the method were further ascertained by performing recovery studies via a spike method. The accuracy of the method, expressed as relative error, was satisfactory. No interference was observed from concomitant substances normally added to the tablets. DRO was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. DRO was found to degrade significantly in acid and base stress conditions and to remain stable in thermal, photolytic degradation, oxidative and hydrolytic conditions. The degradation products were well resolved from primary peak and its impurities, proving that the method is stability indicating. The developed method was validated as per International Conference on Harmonization guidelines with respect to specificity, limit of detection, limit of quantification, linearity, accuracy, precision, solution stability and robustness. This method is also suitable for the determination of DRO drug substance and pharmaceutical dosage forms.
