Green LC-MS/MS method for in-vivo pharmacokinetics of mirabegron-encapsulated nanostructured lipid carriers in rat plasma: Integrating white analytical chemistry and analytical quality by design approach

Abstract

Mirabegron (MBG) stands as the top choice for managing overactive bladder, yet its limited aqueous solubility and low bioavailability pose significant challenges. To overcome these hurdles, the objective was to develop and characterize nanostructured lipid carriers (NLCs) for mirabegron, facilitating its controlled release for overactive bladder treatment through the Quality by Design (QbD) approach. The literature showcases several analytical techniques for mirabegron quantification in pharmaceutical formulations and biological fluids, yet most employ toxic organic solvents in their mobile phases, posing environmental risks and threats to aquatic life. To address this concern, a green liquid chromatographic-tandem mass spectrometry method was developed for in-vivo pharmacokinetic assessment of mirabegron-loaded NLCs in rat plasma, utilizing safe organic solvents. The method's development embraced the principles of analytical QbD, aiming to curtail organic waste generation during sample analysis. Rigorous validation was conducted in accordance with the International Council for Harmonization (ICH) Q2 (R1) and M10 guidelines. The developed method found application in both in-vitro drug release kinetics and in-vivo pharmacokinetic investigations of mirabegron-loaded NLCs. Its performance was assessed using the principles of green and white analytical chemistry through a comparative study with existing analytical techniques. The proposed method's exceptional sensitivity, robustness, and eco-friendliness in mirabegron estimation were highlighted by the results. In conclusion, this proposed green analytical approach not only provides a reliable means of mirabegron analysis but also aligns with sustainable practices by minimizing environmental impact and promoting the principles of green and white analytical chemistry and analytical quality by design.