Dried Matrix Spots for the Determination of Opiates and Opioids: Methodological Advances and Applications.

Dried matrix spot (DMS) techniques have gained increasing attention in bioanalytical and forensic toxicology for the detection of opiates and opioids, offering minimally invasive sampling, enhanced sample stability, and simplified storage and transport. This review provides a critical overview of recent methodological advances and applications of DMS across multiple biological matrices, including blood, plasma, urine, and oral fluid. Particular focus is given to sample preparation protocols, extraction strategies, analytical instrumentation, and method performance. Dried blood spots (DBS) remain the most established format; however, alternative matrices such as dried plasma, urine, and saliva spots (DPS, DUS, DSS) are expanding the scope of DMS, particularly in decentralised and point-of-care contexts. Despite clear advantages, such as reduced biohazard risk and compatibility with high-throughput workflows, several limitations persist, including low sample volumes, matrix-specific recovery issues, and lack of standardised procedures. Future efforts should aim to optimise paper substrates, improve solvent-matrix compatibility, and integrate DMS workflows with automated or miniaturised mass spectrometry platforms. Overall, DMS techniques represent a versatile and evolving analytical platform with strong potential for reliable opioid monitoring in both clinical and forensic settings.