LC-MS/MS测定大鼠血浆中莫诺苷血药浓度  

Determination of morroniside concentration in rat plasma by high performance liquid chromatography-tandem mass spectrometry

作　　者：熊山[1,2] 李敬来[2] 朱秀清[2] 王晓英[2] 吕圭源[1] 张振清[2] 

机构地区：[1]浙江中医药大学,浙江杭州310053 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国中药杂志》2013年第19期3378-3381,共4页China Journal of Chinese Materia Medica

基　　金：国家"重大新药创制"科技重大专项(2012ZX09301003-001-007)

摘　　要：莫诺苷是从中药山茱萸ComusofficinalisSieb．＆Zucc．中提取分离获得的环烯醚萜苷类化合物，具有神经保护等多种药理活性。本研究首次采用LC．MS／MS技术建立了大鼠血浆中莫诺苷浓度的测定方法。血浆样品采用蛋白沉淀法，以金丝桃苷作为内标，色谱柱为InertsilC8—3色谱柱（2．1mm×50mm，5μm），流动相为水（含1mmol·L-1甲酸钠）．乙腈梯度洗脱，流速0．4mL·min-1。采用电喷雾离子源（ESI），正离子模式，多反应监测（MRM）。莫诺苷在2—5000μg·L-1（r=0．9957）线性关系良好，最低定量限为2μg·L-1。方法精密度、准确度、回收率和基质效应均符合生物样品测定的要求，适合大鼠血浆中莫诺苷浓度的测定。应用该方法进行莫诺苷在大鼠体内的药代动力学研究，给药剂量为20mg·kg-1，绘制血药浓度一时间曲线，并采用DAS2．0计算得主要药代动力学参数：AUC。为（587．6±290．7）μg·min·L-1，Cmax为（334．2±148．0）μg·L-1，Tmax为（0．6±0．3）h，t1／2为（0．7±0．3）h。Morroniside, an iridoid glycoside extracted from Comus officinalis, has muhiple pharmacological effects such as neuroprotection. This study took the lead in establishing a method for determining morroniside concentration in rat plasma by high per- formanee liquid chromatography-tandem mass spectrometry. Plasma samples were processed with protein precipitation method, with hy- peroside as the internal standard. An Inertsil C8-3 column （2. 1 mm ×50 mm, 5 μm） was adopted, with a mobile phase composed of water （containing 1 mmol · L-1 Sodium formate）-acetonitrile （gradient elution） at a flow rate of 0.4 mL · min-1. Electrospray ioniza- tion （ESI） was adopted in the positive ion mode for multi-reaction monitoring （MRM）. Morroniside showed a good linear relationship ranging between 2-5 000μg· L-1 （r = 0. 995 7）, with the minimum limit of quantification of 2μg· L-1. Its precise, accuracy, re- covery and matrix effect were all in line with the biological sample measurement requirements. Therefore, the method described above was proved to be suitable for the determination of morroniside concentration in rat plasma. To use the method in the pharmacokinetic study on morroniside in rats, oral administration dose shall be set at 20 mg · kg-1 to map the plasma concentration-time curve. Main pharmacokinetic parameters were calculated by DAS 2. 0. Specifically, AUC0-∞ was （587. 6 ± 290.7） μg · min· L-21, Cmax was （334.2±148.0）μg. L-1, Tmax was （0.6±0.3） h, t1/2was （0.7±0.3） h.

关 键 词：莫诺苷 LC-MS MS 药代动力学 

分 类 号：R96[医药卫生—药理学]