Development of two different eco-friendly label-free platforms for analysis of selumetinib.

Abstract

Selumetinib (SEL) is a recently approved medication for paediatric patients who have neurofibromatosis type 1. It is the first approved therapy for this rare, debilitating, and disfiguring disease. Development of proper analytical platforms for SEL analysis in its marketed pharmaceutical formulation (Koselugo^® capsules) and blood plasma is highly warranted. Availability of such analytical tools would ensure SEL capsules' quality and effective therapy. This study introduces, for the first time, the development of two label-free and sensitive platforms for SEL quantification in capsules and human plasma. These platforms are microwave-assisted with an ultraviolet absorbance microplate reader (MW-UV) and reverse-phase high-performance liquid chromatography with a photodiode-array detector (HPLC-PDA). Both platforms employed the SEL native UV absorption as an analytical signal. The MW-UV measured the UV absorption in 96-well transparent plates at 255 nm. The HPLC-PDA involved chromatographic separation of SEL and tozasertib (TOZ), internal standard, on a C18 column both were detected at 255 nm. The optimum procedures of both platforms were established and validated following the ICH guidelines. The linearity ranges were 15-500 μg mL^-1 and 0.8-100 μg mL^-1, with limits of quantification of 15.3 and 3.5 μg mL^-1, for MW-UV and HPLC-PDA, resp. Both platforms displayed high precision with relative standard deviation values ≤ 1.8 %, and high accuracy with recovery ranging from 98.3 to 102.3 %. The platforms were successfully applied to quantify SEL in bulk form, Koselugo^® capsules, and were preliminarily applied to human plasma analysis. Eco-friendliness assessment confirmed the adherence of both platforms to green analytical approaches. MW-UV and HPLC-PDA are simple and fast, enabling high-throughput analysis, thus introducing valuable tools for routine use in quality control and clinical laboratories for SEL quantification.