目的 采用液相色谱-串联质谱法进行丹酚酸B药动学动物实验研究。方法 比格犬静脉滴注丹酚酸B后不同时间经前腿静脉采血。血浆样品经液-液萃取后，以乙腈-水（含0.5%甲酸）：70-30（V/V）作为流动相，采用Symmetry C18（2.0 mm×50 mm，3 μm）柱分离，通过ESI源电离在负离子方式下进行检测，以选择反应监测（SRM）方式。用于定量分析的离子分别为 m/z 717.2→m/z 519.2（丹酚酸B）和 m/z 364.0→m/z 189.0(吲达帕胺，内标)。结果 在该测定条件下丹酚酸B和内标物的保留时间分别为1.03、1.24 min。丹酚酸B的线性范围为10.24～1.200×104 ng/ml；定量下限为10.24 ng/ml,批内、批间精密度（RSD）均小于15%，准确度（RE）在-2.8%～1.9%之间。结论 所建立的LC-MS/MS法专属性强、灵敏度高，已成功用于丹酚酸B血药浓度测定和药动学研究。血中丹酚酸B半衰期较短，体内代谢呈一级线性动力学，符合三室模型。
Abstract
Objective To study the pharmacokinetics of salvianolic acid B in beagle dogs using LC-MS/MS method. Methods Salvianolic acid B in beagle dogs' vein and plasma samples were collected at different time points after administration．After a liquid-liquid extraction process with ethyl-acetate, salvianolic acid B and indapamide were separated on Symmetry C18.The mobile phase was a mixture of acetonitrile and water(containing 0.3% formic acid).Detection was performed on a triple-quadrupole tandem mass spectrometer by selecting the reaction monitoring(SRM)mode via electricity spray ionization(ESI).Quantification was performed using the transitions of m/z 717.2→m/z 519.2 for salvianlic acid B and m/z 364.0→m/z 189.0 for indapamide respectively. Results The nominal retention time for salvianolic acid B and indapamide was 1.03 and 1.24 min, respectively. Linear calibration curves were obtained over the concentration range of 10.24～1.200×104 ng/ml for salvianolic acid B. The lower limit of quantification (LLOQ) of salvianolic acid B of was 10.24 ng/ml. The intra- and inter-day accuracy of assay was less than 15% and the accuracy(RE)was -2.8%～1.9% at all the three QC levels. Conclusions This method has proved to be of high specifcity,sensitivity and has been successfully used for evaluation of pharmacokinetics of salvianolic acid B.The half life is short and metabolization shows a first-order linear pharmacokinetic.
关键词
丹酚酸B /
药动学 /
液相色谱-串联质谱
Key words
salvianolic acid B /
pharmacokinetics /
liquid chromatography-tandem mass spectroscopy(LC-MS/MS)
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