Therapeutic drug monitoring of lamotrigine using capillary electrophoresis: Evaluation of assay performance and quality assurance over a 4-year period in the routine arena

The performance of a capillary zone electrophoresis (CZE)-based assay for lamotrigine (LAMO) in human plasma and serum with complete internal and external quality assurance over an extended period of time is reported. The assay, originally reported by Shihabi and Oles [J. Chromatogr. B 683 (1996) 119], is based upon protein precipitation by acetonitrile and analysis of an aliquot of the acidified supernatant and was adopted in our laboratory for routine use with multi-level internal calibration on different commercial instruments. Evaluation of the calibration and control data of 103 sets of analysis and data from four years of external quality assurance based upon analysis of four-monthly sera containing LAMO and eight other anticonvulsants in sub-therapeutic, therapeutic or toxicological concentration levels revealed the robustness of the CZE-based assay and its suitability for therapeutic drug monitoring of LAMO in a routine setting. CZE data obtained in single determinations were found to compare well with the spike values and the mean of HPLC data determined in 50–70 laboratories. Furthermore, the gathered data were evaluated retrospectively using single-level internal calibration. When applied with caution, this approach was determined to produce slightly higher but otherwise equivalent drug concentrations. For the 4 years of routine operation with external quality control, the reported laboratory ranking was between 19 (out of 67 participating laboratories) and 43 (69). This is the first account of a CZE-based drug assay with complete external quality assessment.