Simultaneous Determination of Levetiracetam, Sodium Valproate, and Olanzapine in Human Plasma by UPLC‐MS/MS for Therapeutic Drug Monitoring

Levetiracetam, sodium valproate, and olanzapine are widely used for epilepsy, but their therapeutic windows and pharmacokinetic variability require TDM. No existing method enables their simultaneous quantification. This study aimed to establish and validate a UPLC-MS/MS method for their simultaneous detection in human plasma. Plasma samples were processed by protein precipitation. Chromatographic separation was achieved with gradient elution (3.0 min total time), and MRM mode was used for detection. The method showed good linearity (R ≥ 0.9956), precision (CV ≤ 7.27%), and accuracy (bias: -8.95% ~ 9.17%). Extraction recoveries were 94.56%-103.98%, with negligible matrix effects. Application to 136 patients showed average concentrations within therapeutic ranges. This UPLC-MS/MS method is rapid, accurate, and suitable for routine TDM of the three drugs, providing a reliable tool for individualized pharmacotherapy.