Simultaneous determination of seven alkaloids in rat plasma by UFLC-MS/MS and its application to a pharmacokinetic study after oral administration of Cerebralcare Granule
Simultaneous determination of seven alkaloids in rat plasma by UFLC-MS/MS and its application to a pharmacokinetic study after oral administration of Cerebralcare Granule
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DOI：
10.1016/j.jchromb.2016.01.062
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发表时间：
2016-04-01
影响因子：
3
通讯作者：
Herry, Sun
中科院分区：
文献类型：
--
作者：
Li Xiaowen;Tong Ling;Herry, Sun
建立了超快速液相色谱-串联质谱法（UFLC-MS/MS），同时测定大鼠口服脑康颗粒后血浆中延胡索乙素、延胡索乙素、α-别隐品碱、四氢小檗碱、四氢黄连碱、四氢Columbamine和脱氢延胡索乙素7种生物碱成分的浓度。血浆样品用含有内标物地西泮的乙腈进行蛋白沉淀预处理。在Phenomenex Kinetex C18色谱柱（100 x 2.1 mm，2.6 μ m）上进行色谱分离，使用由乙腈-0.1%甲酸水溶液组成的移动的相进行梯度洗脱，流速为0.3 mL/min。在电喷雾电离三重四极杆串联质谱仪上使用多反应监测（MRM）和正离子化模式进行检测。对建立的方法进行了充分验证，证明其灵敏度和特异性，大鼠血浆中的定量下限（LLOQ）均小于0.0265 ng/mL。7种生物碱在各自浓度范围内线性关系良好（r>0.9923）。7种生物碱的日内、日间精密度RSD均小于15%，相对误差RE在-2.7%~8.3%之间。大鼠血浆中的提取回收率、基质效应和稳定性均在要求的限度内。应用该方法研究了大鼠口服脑康颗粒后血浆中7种生物碱的药代动力学。(C)© 2016 Elsevier B. V.版权所有。
An ultra fast liquid chromatography-tandem mass sepectrometry (UFLC-MS/MS) method was developed for simultaneous determination of seven active alkaloid components (tetrahydropalmatine, corydaline, alpha-allocryptopine, tetrahydroberberine, tetrahydrocoptisine, tetrahydrocolumbamine and dehydrocorydaline) in rat plasma after oral administration of Cerebralcare Granule. Plasma samples were pretreated by protein precipitation with acetronitrile containing the internal standard diazepam. Chromatographic separation was achieved on a Phenomenex Kinetex C18 column (100 x 2.1 mm, 2.6 mu m) with gradient elution using mobile phase consisting of acetonitrile -0.1% formic acid in water at a flow rate of 0.3 mL/min. The detection was performed on an electrospray ionization triple quadrupole tandem mass spectrometer using multiple reaction monitoring (MRM) with positive ionization mode. The established method was fully validated and proved to be sensitive and specific with lower limits of quantification (LLOQs) all less than 0.0265 ng/mL in rat plasma. Good linearities of seven alkaloids were obtained in respective concentration ranges (r>0.9923). The intra- and inter-day precisions were below of 15% for all the seven alkaloids in terms of relative standard deviation (RSD), and the accuracies were ranged from -2.7% to 8.3% in terms of relative error (RE). Extraction recovery, matrix effect and stability were within the required limits in rat plasma. The validated method was successfully applied to investigate the pharmacokinetics of the seven alkaloids in rat plasma after oral administration of Cerebralcare Granule (CG). (C) 2016 Elsevier B.V. All rights reserved.