Abstract:

This study aimed to develop a simple, effective, and accurate internal quality control (IQC) method for therapeutic drug monitoring (TDM) of levetiracetam (LEV) in the serum of patients with epilepsy and to evaluate its performance using the Westgard multi-rule criteria, thereby ensuring the analytical quality of the assays. A high-performance liquid chromatography method with diode array detection was established and validated for the quantitative determination of LEV in 100 μL of human plasma. Quality control (QC) samples at low, medium, and high concentrations (2.5, 10, and 50 μg/mL) were prepared in-house, and retrospective IQC data associated with routine TDM of LEV in our laboratory were collected for analysis. Levey-Jennings and Z-score charts were generated using Microsoft Excel, and the TDM assays were assessed according to Westgard multi-rules. Calibration curves demonstrated excellent linearity over a LEV concentration range of 1–80 μg/mL, with correlation coefficients ≥ 0.997 and a lower limit of quantification of 0.5 μg/mL. Intra-day and inter-day coefficients of variation for the low, medium, and high concentration QC samples ranged from 1.03% to 6.90% and 1.63% to 8.19%, respectively, while extraction recovery rates were 74.20%–83.85% and 70.65%–83.72%, respectively. The accuracy of the assay ranged from 96.26% to 109.31%. Twenty batches of QC samples were evaluated using Levey-Jennings and Z-score charts in combination with Westgard multi-rules, and none were found to be out of control. Taken together, this internally developed QC method was simple, rapid, reliable, and accurate for routine TDM of LEV. Its application enhanced the reliability and precision of LEV measurement and supported the rational and safe clinical use of this antiepileptic drug.

Key words: Levetiracetam, Therapeutic drug monitoring, Internal quality control, Westgard multi-rule theory