Stress Degradation Studies on Duloxetine Hydrochloride and Development of an RP-HPLC Method for its Determination in Capsule Formulation

Abstract

Duloxetine hydrochloride (HCl) is an antidepressant drug prescribed for major depressive disorders, pain related to diabetic peripheral neuropathy, and stress urinary incontinence. In the present study, degradation behavior of duloxetine HCl was studied by subjecting the drug to various International Conference on Harmonization-recommended stress conditions. Also, a stability-indicating high-performance liquid chromatography method was established for analysis of the drug in the presence of various degradation products. An acceptable separation of the drug and its degradation products was achieved on a C-8 column at 40 degrees C using a mobile phase comprised of phosphate buffer (pH 2.5)-methanol-tetrahydrofuran in the ratio of 50:40:10 at a flow rate of 1 mL/min. The detection wavelength was 232 nm. The method was validated for linearity, precision, accuracy, selectivity, specificity, and robustness. The method was found to be linear over a concentration range of 1-100 microg/mL (n = 6). The value of slope was found to be 85.735 mV/s ppm with correlation coefficient of 0.9994 and relative standard deviation (RSD) of 0.87%. RSD values ranged from 0.20% to 0.82% in the case of intra-day precision studies, whereas the values ranged from 0.63% to 1.57% in the case of inter-day precision. The drug was found to be stable on exposure of 30% H(2)O(2) for 48 h. It was found to be highly unstable in acidic conditions, as 41.35% degradation was observed in 0.01N HCl at 40 degrees C after 8 h. Degradation was also observed in alkaline and neutral conditions (2.83% and 42.75%, respectively) on refluxing the drug for 1 h. The drug was stable under photolytic and thermal stress on exposure in solid form but showed considerable degradation in solution form.