Simultaneous determination of lacosamide and perampanel concentration in human plasma by LC-MS/MS / 中国药房

ABSTRACT

OBJECTIVE To establish a method for simultaneous determination of two third-generation anti-epileptic medicines such as lacosamide and perampanel in human plasma and apply this method in clinical practice. METHODS Using clozapine as internal standard， the concentrations of lacosamide and perampanel of plasma samples in 10 epileptic patients were determined by LC-MS/MS after protein precipitation with acetonitrile and dilution with acetonitrile-water （20∶80，V/V）， and the plasma minimum concentrations were obtained by dilution of multiple. The determination was performed on Welch Ultimate XB-C18 column， with mobile phase A consisted of 10 mmol/L ammonium formate and mobile phase B consisted of methanol-acetonitrile-isopropanol （0.2% formic acid） mixed solution （7∶1.5∶1.5， V/V/V） for gradient elution at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃ ， and the sample size was 5 μL. The electrospray ion source and multi-reaction monitoring mode were used for positive iron scanning. The ion pair used for quantitative analysis of lacosamide， perampanel and internal standard were m/z 251.2→ 144.1， m/z 350.2→219.2 and m/z 327.2→270.0， respectively. RESULTS The linear ranges of lacosamide and perampanel were 0.001 25-0.125 μg/mL（r＞0.99）， 0.037 5-3.75 ng/mL （r＞0.99）； the limits of quantification were 0.001 25 μg/mL and 0.037 5 ng/mL， respectively. The precision and accuracy within and between batches， extraction recovery rate， matrix effect， and stability all met relevant requirements. The minimum concentrations of lacosamide in No. 1-5 patients were 5.3-12.2 μg/mL， and the minimum concentrations of perampanel in No.6-10 patients were 208-510 ng/mL， respectively. CONCLUSIONS The established method is simple， rapid and suitable for the therapeutic drug monitoring of lacosamide and perampanel.