Surface-enhanced Raman spectroscopy coupled with DFT for sensitive detection of tadalafil in complex matrices

Abstract

Tadalafil (TDF), a widely prescribed phosphodiesterase-5 inhibitor, is not only a clinically important pharmaceutical for erectile dysfunction but also a frequently encountered adulterant in counterfeit supplements, raising serious public health and regulatory concerns. This study presents a novel and integrated approach for the sensitive and selective detection of TDF in complex commercial matrices, combining experimental Surface-Enhanced Raman Scattering (SERS) spectroscopy with Density Functional Theory (DFT) simulations. The molecular geometry of TDF was optimized at the B3LYP/6–311 G(d) level, and theoretical Raman and SERS spectra were generated using a mixed basis set. A molecular electrostatic potential (MEP) map was constructed to identify key adsorption sites, offering mechanistic insights into SERS enhancement. Experimentally, gold-capped silicon nanopillar (AuNP) substrates enabled detection of TDF across a wide concentration range (0.75–100 µM). Through SERS mapping and calibration, we established a linear correlation between signal intensity and TDF concentration. Most importantly, the method demonstrated real-world applicability by successfully detecting TDF in spiked commercial multivitamin tablets. Finally, this work provides a robust sensing platform for detecting illicit pharmaceutical adulterants, bridging theoretical modeling with practical SERS analytics, and offering valuable tools for regulatory monitoring and consumer safety.