目的：建立同时检测Beagle 犬血浆中四氢巴马汀、脱氢紫堇碱、小檗碱和巴马汀的分析方法，并应用有机溶剂沉淀法提取含药血浆中的成分。方法：采用C18 反相柱，流动相为乙腈-0.1%甲酸水 溶液梯度洗脱，质谱采用多反应监测（MRM）方式进行正离子检测。结果：定量分析的离子对（m/z）为：366.2/350.2（四氢巴马汀）、356.2/191.2（脱氢紫堇碱）、336.2/320.2（小檗碱）和352.2/336.2（巴马汀）。测定血浆中四氢巴马汀、脱氢紫堇碱和小檗碱的线性范围均为0.0488~50 μg/L，巴马汀为0.0488~100 μg/L，这4 种成分的定量下限均为0.0488 μg/L，该方法的精密度、准确度和稳定性均符合要求。结论：该法选择性强、灵敏度高、操作简便，可用于血浆中这4 种生物碱的药代动力学研究

A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated for the simultaneous quantification of tetrahydropalmatine (THP), dehydrocorydaline (DHC), berberine (Ber) and palmatine (Pal) in dog plasma. The compounds were pretreated by protein precipitation using organic solvent. Chromatographic separation was achieved on a reversed-phase C18 column with the mobile phase of acetonitrile - water (0.1% acetic acid) and step gradient elution resulted at a flow rate of 0.60 mL/min. A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the positive ion mode. Quantification was performed using multiple reaction monitoring (MRM) of the transitions m/z 366.2/350.2 (THP), 356.2/191.2 (DHC), 336.2/320.2 (Ber) and 352.2/336.2 (Pal). The method showed excellent linearity over the concentration range of 0.0488-50 μg/L for DHC, THP, Ber and 0.0488-100 μg/L for Pal. The low limits of quantification were at 0.0488 μg/L. The precision, accuracy and stability of the analytes meet the requirements. The method was sensitive, accurate and rapid. It can be applied in the determination of plasma concentration of four alkaloids.

国家自然基金项目（81102795）：中药复方指征药代动力学的深入研究，负责人：林力；国家自然基金重点项目（30830118）：有效中药复方功效的指征性物质基础研究，负责人：刘建勋；科学技术部国家科技重大新药创制专项（2009ZX09031-005-007）：中药药效评价研究平台，负责人：刘建勋。