Jain, Jainendra, K., Sujatha, T., Sheelarani, Trivedi, Harshal, Rahul, Khemchandani and Samanthula, Gananadhamu (2025) 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. 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, 40 (12). pp. 1-12. ISSN 2025; 40:e70376

Abstract

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 Δλ = 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.

Item Type:	Article
Keywords:	cleaning validation, darolutamide, enzalutamide, first-derivative synchronous fluorescence, green chemistry, quality by design
Date Deposited:	23 Dec 2025 00:45
Last Modified:	23 Dec 2025 00:45
URI:	https://oak.novartis.com/id/eprint/59478