Determination of levetiracetam concentration in serum by LC-MS/MS
Objective To develop a method for determination of levetiracetam in human serum by LC-MS/MS,and it was applied to therapeutic drug monitoring in epilepsy patients.Methods Using levetiracetam-D6 as internal standard,the serum samples were tested after protein precipitation.The Kinetex XB-C18(50.0 mm x3.0 mm,2.6 μm)was used,the mobile phase consisted of methanol:0.01％formic acid water solution,gradient elution,the flow rate was 0.4 mL·min-1,and the column temperature was 40 ℃.The injection volume was 1 μL.Electron Spray Ionization source was applied and operated in multiple reaction monitoring mode.The quantitative analysis transitions were m/z 171.1→154.2(levetiracetam)and m/z 177.1→160.1(levetiracetam-D6).The specificity,lower limit of quantitation,linearity,precision,accuracy and stability were investigated.The method was applied to 82 cases of epilepsy patients for therapeutic drug monitoring.Results The calibration curve was y=0.573 7x+0.125 0(r=0.999 6),linear was within the range of 1-100 μg·mL-1 for levetiracetam in human serum.The relative standard deviation(RSD)of intra and inter precision were less than 3％.The recovery were between 93.67％-97.61％.The range of serum concentration of levetiracetam in 82 epilepsy patients was 1.14-22.07 μg·mL-1.Conclusions The method for determining levetiracetam concentration is simple,fast,sensitive,specific and accurate,which can be used for the therapeutic drug monitoring in epilepsy patients.
levetiracetamliquid chromatography tandem-mass spectrometrytherapeutic drug monitoring
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