Determination of lamotrigine and its metabolites in human plasma by liquid chromatography-mass spectrometry

Ther Drug Monit. 2006 Oct;28(5):603-7. doi: 10.1097/01.ftd.0000245779.64080.30.


A method based on electrospray ionization liquid chromatography-mass spectrometry was developed for the quantitative determination of lamotrigine and three of its reported metabolites, lamotrigine-2-N-glucuronide, lamotrigine-2-N-methyl, and lamotrigine-2-N-oxide in human blood plasma. The method utilized sample preparation by precipitation of proteins with acetonitrile, chromatographic separation on a reversed-phase system by gradient elution, and monitoring of the protonated molecular ions. Two internal standards, 3,5-diamino-6-(2-methoxyphenyl)-1,2,4-triazine and morphine-3-glucuronide-D3, were utilized to achieve precise quantification. The method validation comprised a demonstration of an agreement in the quantification of lamotrigine with that of a routine HPLC-UV method. The limits of detection were between 0.05 and 0.16 micromol/L. The method was employed for the measurement of clinical samples collected from 55 patients in steady-state prior to the dose intake (trough level). Lamotrigine and the 2-N-glucuronide were typically detected, while the N-methyl and N-oxide metabolites were detected only rarely. The median lamotrigine plasma level was 24.0 micromol/L (range, 4.3 to 64 micromol/L), the median 2-N-glucuronide level was 2.4 micromol/L (range, <0.05 to 24 micromol/L), and the median lamotrigine 2-N-glucuronide/lamotrigine ratio was 0.11 (range, <0.01 to 0.64). In conclusion, this liquid chromatographic-mass spectrometric method is suitable for simultaneous determination of lamotrigine and its metabolites in human plasma.

MeSH terms

  • Anticonvulsants / blood
  • Anticonvulsants / metabolism*
  • Chromatography, High Pressure Liquid
  • Chromatography, Liquid / methods*
  • Drug Monitoring / methods*
  • Humans
  • Lamotrigine
  • Mass Spectrometry / methods*
  • Triazines / blood
  • Triazines / metabolism*


  • Anticonvulsants
  • Triazines
  • Lamotrigine