Development and Validation of Stability Indicating RP HPLC method for the estimation of armodafinil and Characterization of its base Degradation Product by LC-MS/MS

Abstract

The present work focuses on the development and validation of a rapid, selective and reliable stability indicating reverse phase High Performance Liquid Chromatographic method for the quantitative analysis of Armodafinil (ARM). Armodafinil is a eugeroics drug used for treatment of narcolepsy and shift work sleep disorder and also as an adjunctive treatment for obstructive sleep apnea. The separation was carried out on a Hibar Purospher C18 (250 mm × 4.6 mm; 5μ) column by using 0.01 M ammonium formate (pH 4.5, Adjusted with acetic acid) and methanol as mobile phase in the ratio of 45:55 % v/v. The flow rate was maintained at 1 mL/min and the eluents were monitored at 220 nm. Stress studies were carried out with 1 mg/mL of the drug solution, starting with mild conditions and followed by intrinsic conditions to achieve sufficient degradation. Armodafinil underwent extensive degradation under basic hydrolysis condition. The unknown degradation product formed (DP I; 6.59±0.2 min) under the basic degradation condition was separated on a semi preparative HPLC, characterized by UPLC-Q-TOF and its fragmentation pathway was proposed. The proposed structure of the degradation product was confirmed by HRMS analysis. The developed stability indicating LC method was validated with respect to accuracy, precision, specificity/selectivity and linearity. The degradation product was characterized and reported.