Therapeutic monitoring of levetiracetam: comparison of a new immunological method and the reference method in high-performance liquid chromatography

Objectives: Therapeutic monitoring of the levetiracetam, a new anti-convulsant drug may be indicated in patients whose conditions could alter the pharmacokinetic characteristics, in the customization of individual dosage and in the evaluation of patient compliance. In this study, the validated Bio-Rad HPLC method currently in use is compared to the immunological ARKTM method with advanced statistical tools for levetiracetam dosing. Methods: Levetiracetam concentrations of 63 samples were determined using 1) "Levetiracetam by HPLC" kits from Bio-Rad (Hercules, CA) on the Agilent 1100 HPLC system and 2) immunological "ARKTM Levetiracetam" from ARK Diagnostics Inc. (Fremont, CA) on the CDx90 platform from Thermo Fisher Scientific Inc. Results: Intralaboratory imprecision and bias of the new method, assessed over a 20-day period, were 7.4% and 0.5% at 7.5 μg/mL, 4.5% and 1.9% at 30 μg/mL, and 3.1% and 2.0% at 75 μg /mL, respectively. Passign-Bablok regression analysis (X: Bio- Rad, Y: Ark) showed a nonsignificant intercept of 0.16 (95% CI -0.55- 0.72) and a marginally significant slope of 0.95 (95% CI ,90-0.99) suggesting minimal proportional systematic error. The Bland- Altman analysis also showed minimal systematic bias of 1.0 mg/mL (95% CI 0.32-1.69) with 95% HPLC-Ark differences ranging from -4.3 (95% CI -5.52- (-) 3.16) and 6.3 (95% CI 5.16-7.52). The data showed that the values obtained from the two methods are to be considered identical both within the intrinsic imprecision as well as for the analytical quality specifications (maximum permissible error 15%). Conclusions: The new ARKTM method on the CDx platform is acceptable and can be used to measure routine levetiracetam concentration. In particular, since the immunological method drastically lowers the TAT it is easier and immediate to adjust the dosage in critical patients.