Determination of lamotrigine in human plasma using liquid chromatography‐tandem mass spectrometry

• Published in: Neuropsychopharmacology reports Vol. 39; no. 1; pp. 48 - 55
• Main Authors: Itabashi, Shogo, Bito, Rina, Nishina, Maika, Fukumoto, Maki, Soda, Midori, Doi, Mitsunori, Usui, Shigeyuki, Kitaichi, Kiyoyuki
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2019; John Wiley and Sons Inc; Wiley
• Subjects: Acids; Calibration; Chromatography; Convulsions & seizures; Drugs; Epilepsy; Experiments; lamotrigine; liquid chromatography‐tandem mass spectrometry; Mass spectrometry; Methods; Nitrogen; Original; Plasma; plasma concentration; Quality control; Scientific imaging; Software; solid‐phase extraction; Studies; United States > US; Japan; epilepsy; liquid chromatography-tandem mass spectrometry; plasma concentration; lamotrigine; solid-phase extraction
• ISSN: 2574-173X; 2574-173X
• DOI: 10.1002/npr2.12045

Aim Lamotrigine (LTG) is a widely used anti‐epileptic drug that is administered to avoid seizures and to maintain seizure‐free status. However, several factors reportedly cause individual differences of plasma LTG levels, and the therapeutic target range of LTG varies between individuals. Thus, to optimize effective doses of LTG, we developed a rapid and simple method for determining plasma LTG concentrations. Methods Lamotrigine and the internal standard papaverine were extracted from human plasma using solid‐phase extraction. After filtration, 5‐μL aliquots of final samples were injected into the liquid chromatography‐tandem mass spectrometry instrument and LTG and internal standard were separated using a Cadenza CD‐C18 column (100 × 2 mm, 3 μm) with 0.1% formic acid in water/acetonitrile (2/1, v/v). Results The calibration curve was linear from 0.2 to 5.0 μg/mL, and assessments of recovery, intra‐ and inter‐day precision and accuracy, matrix effects, freeze and thaw stability, and long‐term stability demonstrated good reproducibility. Retention times of LTG and internal standard were 1.6 and 2.0 minutes, respectively, and the total run time was 3.5 minutes for each sample. Conclusion We developed a rapid and simple method for determining plasma LTG concentrations. The present novel system could be used to inform LTG dose adjustments for individual patients. We developed a rapid and simple method for determining plasma concentrations of LTG showing good validation for a relatively wide range (0.2‐5.0 μg/mL). The present method can inform estimates of plasma concentrations of LTG to clinicians within 1 hour of sample collection.