HPLC-ESI-MS法测定人血浆中依普利酮的浓度及其药代动力学研究(英文)

Establishment of HPLC-ESI-MS method for the determination of eplerenone in human plasma and its pharmacokinetics

建立测定人血浆中依普利酮浓度的HPLC-ESI-MS法。依普利酮血浆样品采用乙酸乙酯提取,色谱柱为反相色谱C18柱,流动相为10 mmol.L-1醋酸铵水溶液-甲醇(30∶70,v/v)。质谱离子源为电喷雾离子化(ESI)源,选择性离子检测方式检测;血浆样品在2～4000 ng.mL-1内线性良好,定量下限为2 ng.mL-1。本文采用该方法对健康受试者的人体药代动力学进行研究,3个单剂量(25 mg、50 mg和100 mg)口服给药后的药代动力学参数分别为t1/2:(4.9±2.1)、(4.7±1.5)、(5.9±1.2)h;AUC0-∞:(4402±1735)、(8150±2509)、(13783±4102)μg.h.L-1;MRT:(6.2±2.1)、(6.6±1.3)、(7.2±1.6)h;多剂量口服给药50 mg后药代动力学参数为t1/2:(6.1±1.7)h;AUCss:(10 071±4 220)μg.h.L-1;MRT:(8.1±2.3)h;DF:(3.2±1.0)。

A sensitive high performance liquid chromatography-electrospray ionization-mass spectrometry （HPLC-ESI-MS） method was established for the determination of eplerenone （EP） in human plasma. The plasma samples of EP were extracted with ethyl acetate and separated by HPLC on a reversed phase C18 column with a mobile phase of 10 mmol·L^-1 ammonium acetate water solution-methanol （30 ： 70, v/v）. EP was determined with electrospray ionization-mass spectrometry （ESI-MS） in the selected ion monitoring （SIM） mode. The calibration curves were linear over the range of 2-4 000 ng.mL^-1 for EP. The lower limit of quantification was 2 ng.mL^-1. The method has been successfully applied in the pharmacokinetic study of the EP tablets. The main pharmacokinetic parameters of EP after oral administration of 25 mg, 50 mg, 100 mg were as follows, t1/2： （4.9 ± 2.1）, （4.7 ± 1.5）, （5.9 ± 1.2） h; AUC0-∞： （4 402 ± 1 735）, （8 150 ± 2 509）, （13 783 ± 4 102） μg.h.L^-1; and MRT： （6.2 ± 2.1）, （6.6 ± 1.3）, and （7.2 ± 1.6） h. Parameters of EP after oral administration of multiple doses of 50 mg were as follows, t1/2：（6.1 ± 1.7） h; AUCss： （10 071 ± 4 220） μg.h.L^-1; MRT： （8.1 ± 2.3） h; and DF： （3.2 ± 1.0）.