A rapid and sensitive method for determination of escitalopram in human plasma and its application in pharmacokinetic study by liquid chromatography-tandem mass spectrometry / 中国临床药理学与治疗学

ABSTRACT

AIM: To determine the concentration of escitalopram in human plasma by HPLC-MS/MS and investigate the pharmacokinetics of escitalopram. METH-ODS The method involved protein precipitation with methanol. The chromatographic separation was achieved within 6.0 min by using methanol-water with 15 mmol·L-1 ammonium acetate-formic acid (7228O.1, v/v/v) as mobile phase and a Lichrospher CN 150 mm×4.6 mm analytical column. The analytes were detected using an electrospray ionization tandem mass spectrometry in SRM mode. Detection of the ions was performed by monitoring the transitions of m/z 325.0 to 234.0 for escitalopram and m/z 409.1 to 238.1 for amlodipine (intemal standard), respectively. RESULTS:The standard curve was linear ( r = 0. 999) over the concentration range of 0.20 - 50.00 ng· ml- 1. Accuracy and precision were below the acceptance limits of 15%. The recoveries of escitalopram ranged from 96.0% to 103.6%. The lower limit of quantification for escitalopram was 0.20 ng· ml-1 using 200 μl plasma sample.The pharmacokinetic parameters of escitalopram after a single oral dosing of escitalopram oxalate tablet (10 rog)to ten healthy male volunteers were achieved. The Cmax, Tmax, AUC0-t, AUC0-∞, t1/2 and Ke of escitalopram were 9.21±2.10 ng·ml-1 , 3.75±1.04 h, 514.6±152.3 ng·h·ml-1 ,540.5±162.3 ng·h·ml-1 , 34.06±7.71 h and 0.021±0.004 h-1,respectively. CONCLUSION:The determination of concentration of escitalopram in human plasma by HPLC-MS/MS method was repid, sensitive and reliable. It can be used for clinical pharmacokinetic study of escitalopram.