Analytical quality by design (AQbD)-assisted bioanalytical method for the estimation of Lasmiditan in human plasma by reverse phase-high performance liquid chromatography (RP-HPLC).

Abstract

Migraine is a complex neurological condition that often involves a severe headache characterized by moderate to severe throbbing. Lasmiditan a novel ditan approved by USFDA in 2011 to treat migraine. This contemporary research elaborates the systematic development and validation of Reverse Phase-High Performance Liquid Chromatography bio analytical method for estimating Lasmiditan in human plasma employing analytical quality by design. Bio analysis employing protein precipitation was performed to extract Lasmiditan from human plasma using Dolutegravir as the internal standard. Design of Experiments was incorporated employing central composite design, and the methodology was assessed for critical analytical attributes by varying the critical quality attributes using Design Expert Software Version 13.0. The chromatographic conditions optimized were symmetry C18 (150 × 4.6 mm, 5 μ) column, mobile phase 0.1% orthophosphoric acid: acetonitrile (70:30 (v/v) with a flow rate of 1.0 mL/min at detection wavelength of 260 nm and column temperature of 30°C. Validation studies indicated linearity between 20 and 800 ng/mL (r2 = 0.999), whereas accuracy and precision portrayed a 98.79% recovery. Succinctly, current work exemplifies the significant merits of analytical quality by design approach toward the holistic process in bioanalytical method validation. Furthermore, the method was evaluated using the Whiteness Assessment Tool (Blue Applicability Grade Index), yielding a high score of 82.5, indicating superior performance in terms of analytical efficiency, environmental friendliness and operator safety. Thus, the developed method can be applied for estimation of preclinical and clinical samples of Lasmiditan with improved accuracy and precision.