Pharmaceutical drug monitoring: the role of oral fluid sampling

Oral fluid has attracted increasing interest as an alternative biological matrix for monitoring pharmaceutical compounds in clinical and forensic toxicology. Its noninvasive nature, simple collection procedures, and suitability for repeated sampling make it particularly attractive for large-scale drug screening, medical diagnosis, long-term treatment monitoring, and point-of-care applications. Compared with blood sampling, oral fluid collection is better accepted by patients and does not require trained personnel, facilitating its use in decentralized or real-time testing scenarios. In addition, drug concentrations in oral fluid frequently reflect the pharmacologically active unbound fraction of compounds, which may enhance its clinical relevance for individualized dosing and evaluation of therapeutic response. Several studies have reported meaningful correlations between drug concentrations measured in oral fluid and those determined in blood (plasma or serum) for different therapeutic classes, including antiepileptics, antidepressants, analgesics, antibiotics, and immunosuppressants. These characteristics support the growing interest in oral fluid as a useful matrix for therapeutic drug monitoring strategies aimed at optimizing treatment while reducing the risk of adverse effects. This review summarizes and critically discusses recent developments in analytical approaches for the detection of pharmaceutical compounds acting on the central nervous system in oral fluid and their potential application in drug monitoring.