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. 2019 Mar;39(1):48-55.
doi: 10.1002/npr2.12045. Epub 2019 Jan 2.

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

Shogo Itabashi  1 , Rina Bito  1 , Maika Nishina  1 , Maki Fukumoto  1 , Midori Soda  1 , Mitsunori Doi  1   2 , Shigeyuki Usui  1 , Kiyoyuki Kitaichi  1
Affiliations

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

Shogo Itabashi et al. Neuropsychopharmacol Rep. 2019 Mar.

Abstract

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.

Keywords: epilepsy; lamotrigine; liquid chromatography-tandem mass spectrometry; plasma concentration; solid-phase extraction.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scheme of sample preparation
Figure 2
Figure 2
Mass spectra of LTG and IS. A, Mass spectra of LTG at Rt of 1.6 min; B, Mass spectra of LTG at Rt of 2.0 min
Figure 3
Figure 3
Typical chromatograms of LTG and IS in plasma. A, Low‐quality control of LTG (0.2 μg/mL, solid lines) and IS (dashed lines); B, High‐quality control of LTG (5.0 μg/mL, solid lines) and IS (dashed lines); C, Blank plasma (LTG‐ and IS‐free sample); D, Standard curve
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