ABSTRACT
A stability-indicating gradient reverse phase liquid chromatographic purity and assay method for duloxetine hydrochloride (DUH) was developed and validated. DUH was subjected to the stress conditions and it is sensitive towards oxidative, acid and hydrolytic degradation. Successful separation of DUH from its two process impurities and one degradation impurity formed under stress conditions was achieved on a Symmetry C18, 250x4.6mm, 5microm column using a gradient mixture of solvent A (0.01M potassium dihydrogen orthophosphate having 0.2% triethyl amine, pH adjusted to 2.5 with orthophosphoric acid) and solvent B (20:80 v/v mixture of acetonitrile and methanol). The flow rate is 1ml/min and the detection wavelength is 230nm. The mass balance was found to be in the range of 99.2-99.7% in all the stressed conditions.
Subject(s)
Antidepressive Agents/analysis , Chromatography, High Pressure Liquid , Chromatography, Reverse-Phase , Drug Contamination , Technology, Pharmaceutical/methods , Thiophenes/analysis , Drug Stability , Duloxetine Hydrochloride , Hydrogen-Ion Concentration , Hydrolysis , Oxidation-Reduction , Reproducibility of ResultsABSTRACT
A novel stability-indicating gradient reverse phase liquid chromatographic (RP-LC) method was developed for the determination of purity of famciclovir (FCV) in presence of its impurities and degradation products. The method was developed using Inertsil ODS 3 V (250 x 4.6 mm, 5 microm) column with mobile phase containing a gradient mixture of solvent A and B. 0.01 M potassium dihydrogen orthophosphate buffer, pH adjusted to 6.0 with 1% potassium hydroxide was used as buffer. Buffer and methanol in 80:20 (v/v) ratio was used as solvent A and buffer and methanol in 20:80 (v/v) ratio was used as solvent B. The gradient program (T/%B) was set as 0/5, 15/30, 25/50, 45/60, 55/5 and 60/5. The eluted compounds were monitored at 215 nm. FCV was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. FCV was found to degrade significantly in oxidative, acid and base degradation conditions and mildly in hydrolytic degradation conditions and stable in thermal and photolytic degradation conditions. The degradation products were well resolved from main peak and its impurities thus proved the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantitation, precision, linearity, accuracy, robustness and system suitability. This method is also suitable for the assay of famciclovir which ranged from 99.9% to 100.2%.
