Green quality by design HPLC approach for the simultaneous determination of Bilastine and Montelukast

Abstract

For the simultaneous estimation of two co-formulated antihistaminic drugs (Bilastine and Montelukast), a novel and eco-friendly reversed-phase HPLC approach with both diode array and fluorescence detection modes was designed. Rather than using the routine methodology, the Quality by Design (QbD) approach was adopted to speed up the method development and to test robustness of the method. To evaluate the effect of variable factors on chromatographic response, a full factorial design was used. The chromatographic separation was performed using isocratic elution on the C18 column. The mobile phase consists of 92% methanol, 6% acetonitrile, and 2% phosphate buffer with 0.1 (v/v) triethylamine adjusted to pH 3, it was pumped at a flow rate of 0.8 mL/min with an injection volume of 20 μL. The developed stability indicating HPLC approach was used to assess the stability of montelukast (MNT). It was subjected to a variety of stress conditions, including hydrolytic (acid–base), oxidative, thermal, and photolytic stress conditions. All of these conditions were found to have relevant degradation pathways. Under the described experimental conditions, MNT degradation followed pseudo-first-order kinetics. The kinetic parameters of its degradation (rate constant and t1/2) were calculated and a proposal for the degradation pathway was postulated.