PDE-5 inhibitors in complex matrices: Recent updates on pretreatment and detection methods

Phosphodiesterase-5 (PDE-5) inhibitors are a class of drugs primarily used to treat male erectile dysfunction. Common medications include sildenafil, tadalafil, and vardenafil. However, issues such as their illegal adulteration pose significant public health concerns. Furthermore, the structural ambiguity and unknown toxicity of analogues illicitly added to health products further increase the risks associated with their use. This review summarizes sample pretreatment methods and detection techniques. Pretreatment methods include common techniques such as dissolution, dilution, protein precipitation, and liquid-liquid extraction, as well as emerging methods like magnetic solid-phase extraction, dispersive liquid-liquid microextraction, and solid-phase microextraction. The application of novel materials, such as covalent organic frameworks, multi-walled carbon nanotubes, and molecularly imprinted polymers, represents a major development direction in the evolution of pretreatment methodologies. Detection methods encompass liquid chromatography-tandem mass spectrometry, gas chromatography-mass spectrometry, and high-performance thin-layer chromatography, among others. Among these, the use of high-resolution mass spectrometry is a current research hotspot. The review critically evaluates the advantages and limitations of existing methodologies, identifies future development directions, and supports the selection of efficient analytical strategies for specific sample matrices and research purposes.