Analytical method validation and feasibility of salivary pregabalin measurement in Japanese volunteers: A pilot study

Abstract

This pilot study evaluated whether salivary pregabalin concentrations reflect plasma levels in Japanese volunteers to support non‑invasive therapeutic drug monitoring (TDM). Four healthy adults received a single 75‑mg orally disintegrating tablet; unstimulated saliva and venous blood were collected 1 hour post‑dose using a standardized passive‑drool protocol with pre‑collection rinsing. Pregabalin was quantified by a high-performance liquid chromatography with fluorescence detection. The assay met bioanalytical performance criteria across both matrices (excellent linearity, recovery > 94.2%, precision ≤ 10%, stability within 5.2%). At 1 hour, median concentrations were 1.96 μg/mL (plasma) and 0.466 μg/mL (saliva). In paired analysis (n = 4), saliva and plasma showed a positive trend (r = 0.838, p = 0.298). Given the small sample size, these results are considered exploratory and demonstrate the feasibility of the analytical approach rather than providing definitive clinical evidence. Under standardized collection conditions, salivary pregabalin concentrations appear to yield clinically interpretable estimates of systemic exposure, warranting validation in larger, multi‑time‑point cohorts to establish actionable saliva‑to‑plasma conversion thresholds and evaluate clinical utility.