Measurement of serum lamotrigine by high performance liquid chromatography using a phenyltriazine as internal...

Lamotrigine, an anti-epileptic drug with a phenyltriazine molecular structure, is commonly measured for therapeutic drug monitoring purposes by high performance liquid chromatography (HPLC) or gas liquid chromatography (GLC). A convenient internal standard is the structurally related phenyltriazine compound BWA725C previously obtainable from the Wellcome Foundation, UK. Irsogladine is also structurally similar to lamotrigine and was therefore tested as a possible replacement for BWA725C. A GLC procedure with thermionic detection (NPD) has been utilized routinely for lamotrigine in our drug monitoring facility. Irsogladine was unsuitable, however, because the retention times of irsogladine and a co-prescribed drug, carbamazepine, were very similar. An HPLC method utilizing a Prodigy Phenomenex ODS3 column performed well using either of the internal standards. The pH of the mobile phase had a distinct impact on the spectra of lamotrigine and BWA725C. A mobile phase at pH 3, with detection at 225 nm was required to effectively resolve lamotrigine from sulthiame and irsogladine from phenobarbitone. Comparison of the HPLC and the existing GLC method with routine patient specimens (n = 43) gave an equation, y = 0.9382x + 0.8238, R(2) = 0.9862. Irsogladine was found to be a suitable internal standard for an HPLC analysis of lamotrigine.