An Eco‐Friendly and Quality‐by‐Design Optimized Synchronous Spectrofluorescence Method for the Simultaneous Determination of Cleaning Residues of Anticancer Drugs Darolutamide and Enzalutamide From Manufacturing Surfaces

A novel, sensitive, and eco-friendly derivatization-free synchronous fluorescence spectroscopic method was developed and optimized for the simultaneous quantification of enzalutamide and darolutamide. A quality-by-design approach was adopted using a screening design followed by Box-Behnken optimization to investigate the effects of photomultiplier tube voltage, solvent, excitation, and emission slit width on fluorescence response. The determination of first-derivative synchronous spectrofluorimetric scan was done at ∆λ = 50 nm, where amplitudes were recorded at 626 nm for darolutamide and 522 nm for enzalutamide without any interference. The method was validated per ICH Q2(R2) guidelines, showing excellent linearity in ranges of 1.0-12.0 μg/mL for enzalutamide and darolutamide with the LOQ value of < 1.0 μg/mL for both drugs. The validated method was successfully applied to pharmaceutical formulations to determine cleaning residues of enzalutamide and darolutamide. The method was applied at the lower level of 2.0 μg/mL for cleaning the residues from stainless-steel surfaces in a manufacturing environment with promising recovery results from rinse and swab methods. The method was evaluated for analytical greenness metrics using Analytical Green Star Area and Multicolor Assessment tools. This study represents the first report of a synchronous fluorimetric method for this drug pair and its usage in the pharmaceutical cleaning process.