LC-MS/MS Method for Quantification of Levetiracetam in Human Plasma and Its Application in Pharmacokinetic Study of Extended-Release Tablets at Fasted And Fed States / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish an LC-MS/MS method for the determination of levetiracetam to investigate the pharmacokinetics of levetiracetam extended-release tablets at fasted and fed states. METHODS: The separation was achieved on a Waters Symmetry C18 column (3.9 mm×150 mm, 5 μm) with mobile phase consisting of acetonitrile-5 mmol·L-1 ammonium acetate and 0.3% formic acid aqueous solution (10/90, V/V). Two subjects were randomly assigned to receive single oral dose of levetiracetam extended-release tablets 1 000 mg after being fasted and fed by a randomized crossover design. The plasma concentrations of levetiracetam were measured by LC-MS/MS. RESULTS: The calibration curve of levetiracetam in human plasma was linear over the concentration rang of 0.100 0-80.00 μg·mL-1. Under fasted and fed conditions, the main pharmacokinetic parameters of levetiracetam were as followsρmax were 20.50 and 19.09 μg·mL-1, AUC0-48 h were 345.4 and 336.3 μg·h·mL-1, tmax were 4.5 and 7.0 h, respectively. CONCLUSION: The method is proved to be convenient, accurate and sensitive, and suitable for the pharmacokinetic study of 1 000 mg levetiracetam extended-release tablets in healthy Chinese volunteers after being fasted and fed. The result suggests that high fat and calories diet has effect on the pharmacokinetics of levetiracetam extended-release tablets, with tmax being delayed.