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

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. The graphical abstract illustrates a SERS-based approach for the detection of TDF, a pharmaceutical compound, using computational and experimental strategies. On the left, a molecular electrostatic potential (MEP) map of the TDF molecule highlights charge distribution regions, supporting interaction site predictions. The central image depicts TDF molecules interacting with a gold nanopillar array, illustrating the SERS enhancement mechanism via localized surface plasmon resonance. On the right, representative SERS spectra show distinct vibrational features of TDF at various concentrations, including a calibration plot inset, demonstrating the sensitivity and linearity of the method for real sample analysis. This integrated approach enables reliable detection of tadalafil in complex matrices such as adulterated herbal supplements.