An LC-MS/MS Method for Quantification of Lamotrigine and Its Main Metabolite in Dried Blood Spots

Abstract

Background: The antiepileptic drug lamotrigine (LTG) shows high pharmacokinetic variability due to genotype influence and concomitant use of glucuronidation inducers and inhibitors, both of which may be frequently taken by elderly patients. Our goal was to develop a reliable quantification method for lamotrigine and its main glucuronide metabolite lamotrigine-N2-glucuronide (LTG-N2-GLU) in dried blood spots (DBS) to enable routine therapeutic drug monitoring and to identify altered metabolic activity for early detection of drug interactions possibly leading to suboptimal drug response. Results: The analytical method was validated in terms of selectivity, accuracy, precision, matrix effects, haematocrit, blood spot volume influence, and stability. It was applied to a clinical study, and the DBS results were compared to the concentrations determined in plasma samples. A good correlation was established for both analytes in DBS and plasma samples, taking into account the haematocrit and blood cell-to-plasma partition coefficients. It was demonstrated that the method is suitable for the determination of the metabolite-to-parent ratio to reveal the metabolic status of individual patients. Conclusions: The clinical validation performed confirmed that the DBS technique is a reliable alternative for plasma lamotrigine and its glucuronide determination.

Therapeutic Drug Monitoring in Psychiatry: Enhancing Treatment Precision and Patient Outcomes

“…Some older studies also suggest a correlation between serum and saliva sampling in measuring lamotrigine concentrations, so this could be a good alternative in order to minimize the invasiveness of monitoring; however, it should be noted that these studies were conducted either in healthy volunteers or in patients with epilepsy, so the validity of saliva sampling in patients with psychiatric disorders is yet to be demonstrated [34][35][36]. Other researchers have recently proposed dried blood spots as an alternative to plasma sampling, with good results in terms of reliability and reduction of invasiveness [37].…”