Evaluation of Salicylic Acid in Saliva for Therapeutic Drug Monitoring of Acetylsalicylic Acid

Abstract

The primary objective of this study was to assess whether saliva could be used as a non-invasive matrix for therapeutic drug monitoring (TDM) of salicylic acid (SA) following administration of acetylsalicylic acid (ASA). Raman spectroscopy was initially explored for this purpose, but the method proved insufficiently sensitive to detect SA in solution. As a result, the study focus shifted to high-performance liquid chromatography with ultraviolet detection (HPLC-UV, both for quantification and to investigate potential correlations between plasma and saliva concentrations. The HPLC-UV method was developed and validated for linearity, precision, specificity, and sensitivity. The clinical study involved nine healthy adults ingested 500 mg ASA, plasma and saliva samples were collected at three time points: baseline, 1 hour, and 2 hours post-administration. Samples were processed with matrix-appropriate methods and analyzed by HPLC-UV. SA was detectable in both plasma and saliva post-administration, with peak concentrations observed at 1 hour. Plasma response remained relatively stable across time points, whereas salivary response displayed greater temporal and inter-individual variability. Consequently, the saliva-to-plasma ratio was inconsistent, limiting the current applicability of saliva as a reliable matrix for TDM of ASA. Further investigation is warranted to elucidate the factors influencing this variability and to establish validated correlations between matrices.