Simultaneous Determination of Four Main Isosteroidal Alkaloids of Bulbus Fritillariae Cirrhosae in Rat Plasma by LC-MS-MS
Simultaneous Determination of Four Main Isosteroidal Alkaloids of Bulbus Fritillariae Cirrhosae in Rat Plasma by LC-MS-MS
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DOI：
10.1007/s10337-012-2247-z
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发表时间：
2012-07-01
期刊：
影响因子：
1.7
通讯作者：
Cui, Hongmei
中科院分区：
文献类型：
--
作者：
Luo, Heng;Zhang, Lei;Cui, Hongmei
建立了一种简便、灵敏、选择性好的LC-MS-MS同时测定大鼠血浆中贝母素、贝母碱、贝母碱和地拉夫碱的方法。以卡马西平为内标。LC-MS-MS系统与电喷雾电离(ESI)源耦合在多反应监测(MRM)模式下进行。异甾体生物碱的转变如下：m/z 432.4->；414.4为贝母素，m/z 430.5->；412.4为贝母素，m/z 428.4->；114.2为贝母碱，m/z 416.5->；105.2为地拉韦，m/z 237.2->；194.2为卡马西平(IS)。样品制备采用添加卡马西平(IS)后的乙酸乙酯液-液萃取法。色谱柱为Welch C18柱(3.5um m，2.1×100 mm)，流动相为甲醇-5 mmol L-1醋酸铵-0.1%甲酸水溶液。保留时间小于8.0min。贝母素和贝母碱的线性范围为0.2~200 ng mL(-1)，贝母碱和地拉韦的线性范围为1.0~200 ng mL(-1)。该方法对相关系数为0.995的所有分析物都是线性的。方法的日内、日间准确度和精密度均可接受。该方法已成功地应用于大鼠灌胃贝母提取物的药代动力学研究。
A simple, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed for simultaneous quantitation of four isosteroidal alkaloids (peimine, peiminine, peimisine, and delavine) in rat plasma. Carbamazepine was selected as internal standard (IS). The LC-MS-MS system coupled with an electrospray ionization (ESI) source was performed in the multiple reaction monitoring (MRM) mode. The transitions of the isosteroidal alkaloids executed as following: m/z 432.4 -> 414.4 for peimine, m/z 430.5 -> 412.4 for peiminine, m/z 428.4 -> 114.2 for peimisine, m/z 416.5 -> 105.2 for delavine, and m/z 237.2 -> 194.2 for carbamazepine (IS). Sample preparation was performed with liquid-liquid extraction using ethyl acetate after carbamazepine (IS) spiked. The separation was performed on a Welch C18 column (3.5 mu m, 2.1 x 100 mm), and a gradient elution of methanol and 5 mmol L-1 ammonium acetate in 0.1 % formic acid aqueous solution was used. The retention time was less than 8.0 min. Linearity was obtained over the concentration range of 0.2-200 ng mL(-1) for peimine and peiminine, and 1.0-200 ng mL(-1) for peimisine and delavine. The method was linear for all analytes with correlation coefficients > 0.995. The intra-day and inter-day accuracy and precision of the assay were acceptable. This method has been successfully applied to the pharmacokinetic study of Bulbus Fritillariae Cirrhosae extract after oral administration to rats.