Quantitation of levetiracetam concentrations in plasma and saliva samples by ultra-performance liquid chromatography-tandem mass spectrometry: Application to therapeutic drug monitoring for pregnant women with epilepsy.

Although levetiracetam (LEV) has favorable linear pharmacokinetic properties, therapeutic drug monitoring (TDM) is necessary for pregnant women with epilepsy. This study aims to build a simple, reliable, and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determining LEV concentrations in plasma and saliva samples, to support the routine TDM of LEV in Chinese pregnant women with epilepsy. The stable isotope-labeled LEV-d6 was used as the internal standard. The extracted samples were analyzed using a UPLC-MS/MS system with positive electrospray ionization. Mobile phase A was water containing 5 mM ammonium acetate and 0.1% formic acid, and phase B was 1:1 methanol-acetonitrile with 0.1% formic acid. The method was validated and utilized to determine LEV concentrations in non-pregnant and pregnant patients with epilepsy. The developed method was validated in both plasma and saliva samples over a concentration range of 0.1-50 μg/mL. The intra- and inter-batch accuracy for LEV ranged from -7.0% to 2.9%, with precisions between 2.7% and 9.3%. In pregnant patients, the mean dose-standardized LEV trough plasma concentrations were significantly lower than those in non-pregnant patients (4.73 ± 2.99 vs. 7.74 ± 3.59 ng/mL per mg/day; P < 0.0001). It is recommended that the TDM of LEV should be routinely performed during the different stages of pregnancy.