Toward needle-free lamotrigine monitoring: Proof-of-concept for saliva and dried saliva spot analysis by LC-MS/MS - a short communication

Abstract

Recent advancements in micro-sampling methods provide non-invasive options for collecting biological samples used in therapeutic drug monitoring (TDM). Lately, alternative matrices such as capillary blood and saliva/oral fluid in the form of dried saliva spots, have attracted considerable interest. These matrices represent a promising approach for TDM, as they could improve accessibility while preserving analytical precision.

The study developed and validated an LC-MS method for lamotrigine quantitation in saliva and Dried Saliva Spots (DSS). Samples were prepared via protein precipitation (methanol: acetonitrile: water, 7:2:1) and dilution, followed by separation on a Luna Omega C18 Polar column and detection in ESI+ mode. An isotopically labelled internal standard was employed, ensuring compliance with EMA guidelines. The linearity was demonstrated for lamotrigine concentrations ranging from 0.20 to 25 mg/L in both dried saliva spot and saliva samples.

Saliva and DSS samples from patients were used to compare lamotrigine concentrations with plasma levels determined by a hospital-accredited laboratory. Findings demonstrated a strong correlation between evaluated matrices and plasma (R = 0.847 for saliva and plasma, and R = 0.839 for DSS and plasma, both p < 0.0001), underscoring the promise of saliva and DSS as substitutes for TDM. This technique improves patient comfort and accessibility through a non-invasive sampling method while ensuring accuracy.

These findings provide a foundation for broader clinical implementation of alternative-matrix TDM, representing a significant step toward patient-centred, accessible pharmacotherapy and enabling improved LTG monitoring in ambulatory and remote settings.