LC-MS/MS测定大鼠血浆中白术内酯Ⅰ、Ⅱ、Ⅲ的浓度及苍术-香附提取物在大鼠体内的药动学研究  

Determination of AtractylenolideⅠ,ⅡandⅢin Rat Plasma by LC-MS/MS and Study on Pharmacokinetics of Atractylodes-Cyperi rhizoma Extract in Rats

作　　者：曹阳[1] 戴国梁[1] 李斐然 刘美琛 王一清[1] 杭华茜 叶峪 居文政[1] CAO Yang;DAI Guoliang;LI Feiran;LIU Meichen;WANG Yiqing;HANG Huaxi;YE Yu;JU Wenzheng(Department of Clinical Pharmacology,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China)

机构地区：[1]南京中医药大学附属医院临床药理科,南京210029

出　　处：《中国药学杂志》2023年第17期1582-1588,共7页Chinese Pharmaceutical Journal

基　　金：江苏省自然科学基金面上项目资助(BK20211394);江苏省中医药领军人才项目资助(SLJ0208);江苏省中医药科技发展计划面上项目资助(MS2021011);江苏省研究生科研与实践创新计划项目资助(KYCX22_1917)。

摘　　要：目的建立液相色谱-串联质谱法(LC-MS/MS)检测大鼠血浆中白术内酯Ⅰ、白术内酯Ⅱ、白术内酯Ⅲ浓度,研究苍术-香附提取物灌胃后大鼠体内3种活性成分的药动学特征。方法以苯海拉明为内标,血浆样品采用乙酸乙酯液-液萃取法处理,采用ACQUITY UPLC BEH-C_(18)色谱柱(2.1 mm×50 mm,1.7μm),流动相为乙腈-体积分数0.05%甲酸水,通过电喷雾离子源进行正离子扫描,多反应监测技术(multiple reaction monitoring,MRM)检测模式。检测离子:m/z 231.2→185.1(白术内酯Ⅰ)、m/z 233.2→187.1(白术内酯Ⅱ)、m/z 249.2→231.1(白术内酯Ⅲ)、m/z 256.2→167.1(苯海拉明)。利用DAS 3.2.2软件计算药动学参数。结果白术内酯Ⅰ、白术内酯Ⅱ、白术内酯Ⅲ的线性范围分别为0.3150~20.00、0.3150~20.00、3.150~200.0 ng·mL^(-1),方法学的各项指标均符合要求。苍术-香附提取物灌胃给药后的3种活性成分的药-时曲线呈双峰现象,t_(1/2)分别为(12.593±3.27)(14.868±5.51)(9.736±4.08)h;t_(max)分别为(0.458±0.29)(0.389±0.13)(0.347±0.08)h;ρ_(max)分别为(7.719±4.93)(13.43±3.50)(153.702±23.51)ng·mL^(-1);AUC_(0-t)分别为(42.592±19.45)(64.132±15.12)(1042.156±168.43)ng·h·mL^(-1)。结论该LC-MS/MS操作简便,灵敏度高,满足了严格的方法学验证,可用于苍术-香附提取物在大鼠体内药动学研究。OBJECTIVE To establish an LC-MS/MS method for determination of atractylenolideⅠ,atractylenolideⅡand atractylenolideⅢin rat plasma,and study the pharmacokinetics of the three active components of Atractylodes Rhizoma-Cyperus Rhizoma extract in rats.METHODS Diphenhydramine was used as the internal standard,and the plasma samples were treated by liquid-liquid extraction with ethyl acetate.ACQUITY UPLC BEH-C_(18) column(2.1 mm×50 mm,1.7μm)was used,and acetonitrile-0.05%formic acid water was used as the mobile phase.Positive ion scanning was carried out by electrospray ion source(ESI).Multiple reaction monitoring(MRM)was used to monitor precursor to product ion transition of m/z 231.2→185.1 for atractylenolide I,m/z 233.2→187.1 for atractylenolideⅡ,m/z 249.2→231.1 forⅢ,and m/z 256.2→167.1 for IS(diphenhydramine).Pharmacokinetic parameters were calculated by DAS 3.3.2 software.RESULTS The linear ranges of atractylenolideⅠ,atractylenolideⅡand atractylenolideⅢwere 0.3150-20.00,0.3150-20.00 and 3.150-200.0 ng mL^(-1),respectively.Indicators of the method validation were in line with requirements.The drug concentration-time curves of the three active components of the extract showed double peaks,and the pharmacokinetic parameters were as follows:t_(1/2):(12.593±3.27)(14.868±5.51)(9.736±4.08)h,tmax:(0.458±0.29)(0.389±0.13)(0.347±0.08)h,ρ_(max):(7.719±4.93)(13.43±3.50)(153.702±23.51)ng·mL^(-1),AUC_(0-t):(42.592±19.45)(64.132±15.12)(1042.156±168.43)ng·h·mL^(-1).CONCLUSION The LC-MS/MS method is simple and sensitive and can be used to study the pharmacokinetics of Atractylodes Rhizoma-Cyperus Rhizoma extract in rats.

关 键 词：苍术-香附药对 白术内酯 药动学 液相色谱-串联质谱法 

分 类 号：R969.1[医药卫生—药理学]