LC-MS/MS determination and comparative pharmacokinetics of strychnine, brucine and their metabolites in rat plasma after intragastric administration of each monomer and the total alkaloids from Semen Strychni
LC-MS/MS determination and comparative pharmacokinetics of strychnine, brucine and their metabolites in rat plasma after intragastric administration of each monomer and the total alkaloids from Semen Strychni
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DOI：
10.1016/j.jchromb.2015.11.012
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发表时间：
2016-01-01
影响因子：
3
通讯作者：
Liu, Yiming
中科院分区：
文献类型：
--
作者：
Lin, Aihua;Su, Xiaochun;Liu, Yiming
建立了同时测定大鼠血浆中士的宁、马钱子碱、士的宁和马钱子碱的LC-MS/MS方法。血浆样品用甲醇简单蛋白质沉淀法进行前处理，以盐酸麻黄碱为内标。色谱柱为ZORBAX Eclipse XDB-C-18柱(2.1×150 mm，3.5µm)，用甲醇和10 mM醋酸铵(用甲酸调节pH至4.0)梯度洗脱。在正离子多反应监测(MRM)模式下，以TurbolonSpray电离(ESI)进样，用质谱仪对分析物进行定量。结果表明，士的宁和马钱子碱的线性范围分别为306.3和306.0 ng mL(-1)，线性范围分别为0.510和0.102。日内、日间精密度均小于14.9%，3个质控水平的准确度在89.4%~113%之间。将该方法成功地应用于马钱子碱、马钱子碱、士的宁N-氧化物和马钱子碱N-氧化物在大鼠体内的药代动力学研究。单次口服4个剂量水平的马钱子总生物碱后，士的宁和马钱子碱的C-max、AUC(0-t)均增加，并与口服剂量成正比。在比较药代动力学研究中，各单体与马钱子总生物碱在C-max、AUC等药代动力学参数上无显著差异。单体组士的宁和马钱子碱的平均C-max和AUC略高于马钱子总生物碱组，提示马钱子中的其他生物碱可能会降低马钱子碱和马钱子碱在体内的吸收。(C)2015爱思唯尔B.V.保留所有权利。
A rapid, specific and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the simultaneous determination of strychnine, brucine, strychnine N-oxide and brucine N-oxide in rat plasma. Plasma samples were pretreated via simple protein precipitation with methanol and ephedrine hydrochloride was used as internal standard. Chromatographic separation was carried out on an ZORBAX Eclipse XDB-C-18 column (2.1 x 150 mm, 3.5 mu m) by gradient elution with methanol and 10 mM ammonium acetate (adjusted to pH 4.0 with formic acid). The quantification of the analytes was performed by mass spectrometry with TurbolonSpray ionization (ESI) inlet in the positive ion multiple reaction monitoring (MRM) mode. The results showed that the calibration curve was linear in the concentration range of 0.510 similar to 306.3 ngmL(-1) for strychnine, brucine and 0.102 similar to 306.0 ng mL(-1) for strychnine N-oxide and brucine N-oxide, respectively. The intra- and inter-day precisions were less than 14.9%, and the accuracy ranged from 89.4 to 113% at three QC levels for the 4 analytes. The validated method was successfully applied to the pharmacokinetic study of strychnine, brucine, strychnine N-oxide and brucine N-oxide in rat plasma after oral administration of each monomer and the total alkaloids from Semen Strychni. After single oral administration of the total alkaloids from Semen Strychni at 4 dose levels, C-max, AUC(0-t) of strychnine and brucine increased and were proportional to the oral doses. In comparative pharmacokinetics studies, no significant difference was found between each monomer and the total strychnos alkaloids on the pharmacokinetic parameters such as C-max and AUC. Mean C-max and AUC of strychnine and brucine were slight increased in the monomer groups in comparison to the total strychnos alkaloids groups, which suggested that some other alkaloids in the Semen Strychni may decrease the absorption of strychnine and brucine in body. (C) 2015 Elsevier B.V. All rights reserved.