Main content area

Determination of plasma Levetiracetam level by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS-MS) and its application in pharmacokinetics studies in neonates B Analytical technologies in the biomedical and life sciences

Jenjirattithigarn, Nuttawut, Worachat, Nattha, Horsuwan, Suchawadee, Puangpetch, Apichaya, Prempunpong, Chatchay, Khongkhatithum, Chaiyos, Thampratankul, Lunliya, Prommas, Santirat, Visudtibhan, Anannit, Sukasem, Chonlaphat
Journal of chromatography 2018 v.1085 pp. 13-20
ammonium acetate, anticonvulsants, correlation, formic acid, lamivudine, liquid chromatography, methanol, models, monitoring, neonates, pharmacokinetics, solid phase extraction, tandem mass spectrometry
Levetiracetam (LEV) is an antiepileptic drug which has good safety and efficacy in neonatal seizure (NS), a common incident in neonates with weight <1500 g. The pharmacokinetics for LEV in neonatal populations is yet to be clearly understood. In this study, we developed and validated a method for determination of LEV in plasma by liquid chromatography tandem mass spectrometry for the purpose of pharmacokinetic study.Plasma LEV was spiked with Lamivudine as internal standard before extraction by C18 solid-phase extraction (SPE) cartridge. Chromatography was performed using isocratic elution with mobile phase A: B (10: 90) for 2.0 min with flow rate 0.4 mL/min. The mobile phase was composed of 0.1% formic acid in 10.0 mM ammonium acetate (A) and 100% methanol (B). The injection volume was 1.0 μL and the total run time was 2.0 min. Multiple reaction monitoring (MRM) with electro spray in positive mode was used. The mass transition for LEV was 171.2/126.0 and 230.0/112.0 for IS with retention time of 0.73 and 0.72 min, respectively.A calibration curve range from 0.50–80.0 μg/mL was obtained with a correlation coefficient >0.99 in the quadratic model. Precision and accuracy was within the acceptable range and the intra- and inter-day %CV for three concentrations of QCs were <10%.This method was reliable, accurate and applicable for LEV pharmacokinetic study in neonates with seizure.