Chromatographic determination of antidepressants in plasma and saliva: Towards non-invasive therapeutic monitoring.

Drug monitoring of antidepressants in plasma and oral fluid represents a valuable tool in clinical practice, enabling the optimisation of treatment efficacy and the reduction of adverse effects. Given the significant interindividual variability in antidepressant response-driven by factors such as metabolism, drug-drug interactions, and adherence to therapy-drug monitoring facilitates dose adjustment based on measured drug concentrations, ensuring levels remain within the therapeutic window. This study aimed at developing and validating a robust, rapid, and sensitive method for the simultaneous quantification of 21 selected antidepressants and their metabolites in only 100 μL of plasma and oral fluid. Sample preparation was performed using a simple protein precipitation protocol, followed by analysis via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was validated in accordance with internationally accepted bioanalytical guidelines, demonstrating linearity over the concentration range of 0.98-1000 ng/mL. Limits of quantification were established at 0.98 ng/mL for all analytes across both matrices. The extraction procedure yielded high recovery rates, and the method showed excellent selectivity, sensitivity, precision, and accuracy, confirming its suitability for routine toxicological applications. The validated method was successfully applied to 142 paired authentic plasma and oral fluid specimens from patients undergoing antidepressant therapy. Antidepressant concentrations were determined in both matrices, and treatment adherence was considered high, being confirmed in 88.7 % of patients. Correlation analysis between plasma and oral fluid concentrations produced promising results for several of the compounds under investigation, reinforcing the potential utility of oral fluid as a non-invasive alternative matrix in drug monitoring.