LC/MS/MS法测定人血浆中愈创木酚甘油醚浓度及药动学研究

目的:建立以高效液相色谱-质谱联用法测定人血浆中愈创木酚甘油醚浓度的方法,并研究愈创木酚甘油醚片的人体药动学。方法:碱化的血浆药品经乙酸乙酯萃取后,以甲醇-1%甲酸(70:30)为流动相,对乙酰氨基酚为内标,采用Aquasil C18柱分离。通过液相色谱-串联质谱联用仪,以选择反应监测方式进行检测,定量分析的离子反应分别为m/z199→m/z125(愈创木酚甘油醚)和m/z152→m/z110(对乙酰氨基酚)。结果:愈创木酚甘油醚检测浓度在5·0～2500ng·mL-1范围内线性关系良好(r=0·9953),定量下限为5·0ng·mL-1。20名受试者口服愈创木酚甘油醚片0·2g后的主要药动学参数Cmax为(754·6±190·5)ng·mL-1、t1/2为(0·97±0·12)h、tmax为(0·63±0·22)h、AUC0～t为(1435·8±441·9)ng·h·mL-1、AUC0～∞为(1444·9±449·3)ng·h·mL-1。结论:本方法简便、快速、灵敏,可用于愈创木酚甘油醚的临床药动学研究。

Determination of Guaifenesin in Human Plasma by LC/MS/MS and Its Pharmacokinetic Study

OBJECTIVE:To determine the content of guaifenesin in human plasma samples by LC/MS/MS and to study its pharmacokinetics.METHODS:After being extracted by ethyl acetate,the alkalized plasma samples were separated on aquasil C18 column with methanol-1% methanoic acid(70:30)as mobile phase and paracetamol as internal standard.The detection was performed on a HPLC-triple quadrupole tandem mass spectrometer by selected reaction monitoring(SRM) mode via elect-rospray ionization(ESI).In quantitative analysis,the ionic reaction of guaifenesin was m/z199→m/z125 and that of paracetamol was m/z152→m/z110.RESULTS:The method was linear in the concentration range of 5.0～2 500.0ng·mL-1(r=0.995 3)for guaifenesin,with lower limit of quantification at 5.0 ng·mL-1.The main pharmacokinetic parameters in 20 healthy volunteers after administration of single oral dose of 0.2 mg guaifenesin tablets were the following:Cmax:(754.6±190.5)ng·mL-1;t1/2:(0.97±0.12)h;tmax:(0.63±0.22)h;AUC0～t:(1 435.8±441.9)ng·h·mL-1;AUC0～∞:(1 4 44.9±449.3)ng·h·mL-1.CONCLUSION:The established method is simple,rapid and sensitive,and suitable for clinical pharmacokinetic study of guaifenesin.