UPLC-MS/MS测定大鼠血浆苦参酮的浓度及其药动学研究  

Development of UPLC-MS/MS Method for Determination of Kurarinone in Rat Plasma and Its Application to Pharmacokinetic Study

作　　者：杨志欣[1] 李霞[1] 张文君[2] 王祺茹 单柏松 王海威[1] 刘佳佳[1] 邓伟哲[3] 

机构地区：[1]黑龙江中医药大学药学院,黑龙江哈尔滨150040 [2]哈尔滨商业大学药学院,黑龙江哈尔滨150076 [3]中国人民解放军第211医院,黑龙江哈尔滨150080

出　　处：《中药新药与临床药理》2016年第6期834-839,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：黑龙江省自然科学基金(H2016057);黑龙江中医药大学"优秀创新人才支持计划"项目(2012);国家教育部春晖计划(Z2008-1-15016);黑龙江省教育厅骨干教师基金(1251 G058)

摘　　要：目的建立大鼠血浆中苦参酮UPLC-MS/MS测定方法,研究大鼠静脉、口服苦参酮后的体内药动学。方法采用ACQUITY UPLC~ HSS T3 C_(18)色谱柱,乙腈-0.1%甲酸水为流动相,梯度洗脱,流速0.2 mL·min^(-1),待测血浆样品采用乙酸乙酯液液萃取法制备。MS/MS采用电喷雾离子化电离源(ESI),多反应离子监测(MRM),负离子方式检测,芦丁为内标。监测离子对分别为m/z 437.2→161.1(苦参酮)和m/z 609.3→300.3(芦丁)。DAS 2.0软件处理数据。结果苦参酮在0.1~1000 ng·mL^(-1)的浓度范围内有良好的线性关系(r^2=0.9965);精密度<12.9%,准确度在-7.4%~11.7%之间,平均提取回收率>79.2%。苦参酮静脉给药后T_(1/2z)为(4.0±0.3)h,AUC_(0→∞)为(0.64±0.26)μg·mL^(-1)·h,MRT_(0→∞)为(3.0±0.4)h;口服后T_(1/2z)为(5.6±2.1)h,T_max为(1.7±1.2)h,AUC_(0→∞)为(1.4±0.3)μg·mL^(-1)·h,MRT_(0→∞)为(6.1±1.0)h;苦参酮在大鼠体内的绝对生物利用度约10.7%。结论所建立的UPLC-MS/MS分析方法简便、快速、灵敏、准确,可用于苦参酮大鼠体内药物动力学研究,苦参酮大鼠口服绝对生物利用度偏低。Objective To develop an ultra performance liquid chromatography tandem mass spectrometry（UPLCMS/MS）method for the determination of kurarinone（KR） in rat plasma and to apply it to the pharmacokinetic study of intravenous and oral administration of KR in mice.Methods Analysis was carried out on an ACQUITY UPLC- HSS T3 C18 column using acetonitrile-0.1 % formic acid in water as the mobile phase at a flow rate of 0.2 m L/min.Plasma samples were processed using a liquid-liquid extraction procedure with ethyl acetate.The detection was performed on a triple quadrupole tandem mass spectrometer（MS/MS） by multiple reaction monitoring（MRM） with an electro-spray ionization source（ESI） in negative ionization mode.Ion transitions of m/z 437.2 →161.1 and 609.3 →300.3 were monitored for KR and IS,respectively.All statistical analysis was performed using DAS 2.0 software package.Results The calibration curves of KR exhibited good linearity（r-2=0.9965） in the range of 0.1-1000 ng·m L^-1.All of the intra-day and inter-day precision data were within 12.9 %,the accuracy ranging from-7.4 % to 11.7 %.Their average recoveries were greater than 79.2 %.The pharmacokinetic parameters were as follows：T（1/2z）（4.0 ±0.3）h,AUC（0→∞）（0.64±0.26）μg·m L^-1·h,MRT（0→∞）（3.0±0.4）h for the intravenous administration;T（1/2z）（5.6±2.1）h,Tmax（1.7 ±1.2）h,AUC（0 →∞）（1.4 ±0.3）μg·m L^-1·h,MRT（0 →∞）（6.1 ±1.0）h for the oral administration.The absolute bioavailability of KR was approximately 10.7 %.Conclusion A simple,rapid,sensitive and accurate UPLC-MS/MS method has been developed.The established method has been successfully used for the pharmacokinetic study of KR.However,the results showed that oral use of KR was poorly absorbed with lower F value.

关 键 词：苦参酮 苦参 超高效液相色谱-串联质谱 血药浓度 药物动力学 

分 类 号：R285.5[医药卫生—中药学]