Li Jin-Qi, Wang Jia-Feng, Li Jie, Zhang Shu-Han, He Dan, Tong Rong-Sheng, She Shu-Ya
Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, China.
School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Biomed Chromatogr. 2018 May;32(5):e4182. doi: 10.1002/bmc.4182. Epub 2018 Jan 16.
Senkyunolide I is one of the major bioactive components in the herbal medicine Ligusticum chuanxiong. The aim of this study was to develop and validate a fast, simple and sensitive LC-MS/MS method for the determination of senkyunolide I in dog plasma. The plasma samples were processed with acetonitrile and separated on a Waters Acquity UPLC BEH C column (50 × 2.1 mm, 1.7 μm). The mobile phase consisted of 0.1% formic acid aqueous and acetonitrile was delivered at a flow rate of 0.3 mL min . The detection was achieved in the positive selected reaction monitoring mode with precursor-to-product transitions at m/z 225.1 → 161.1 for senkyunolide I and at m/z 349.1 → 305.1 for an internal standard. The assay was linear over the tested concentration range, from 0.5 ng mL to 1000 ng mL , with a correlation coefficient >0.9992. The mean extraction recovery from dog plasma was within the range of 85.78-93.25%, while the matrix effect of the analyte was within the range of 98.23-108.89%. The intra- and inter-day precisions (RSD) were <12.12% and the accuracy (RR) ranged from 98.89% to 104.24%. The validated assay was successfully applied to pharmacokinetic and bioavailability studies of senkyunolide I in dogs. The results demonstrated that (a) senkyunolide I showed short elimination half-life (<1 h) in dog, (b) its oral bioavailability was >40% and (c) senkyunolide I showed dose-independent pharmacokinetic profiles in dog plasma over the dose range of 1-50 mg kg .
藁本内酯I是中药材川芎中的主要生物活性成分之一。本研究的目的是建立并验证一种快速、简便且灵敏的液相色谱-串联质谱法，用于测定犬血浆中的藁本内酯I。血浆样品用乙腈处理后，在沃特世Acquity UPLC BEH C柱（50×2.1 mm，1.7μm）上进行分离。流动相由0.1%甲酸水溶液和乙腈组成，流速为0.3 mL/min。采用正离子选择反应监测模式进行检测，藁本内酯I的母离子-子离子跃迁为m/z 225.1→161.1，内标的母离子-子离子跃迁为m/z 349.1→305.1。在所测试的浓度范围0.5 ng/mL至1000 ng/mL内，该测定方法呈线性，相关系数>0.9992。犬血浆中的平均提取回收率在85.78% - 93.25%范围内，而分析物的基质效应在98.23% - 108.89%范围内。日内和日间精密度（相对标准偏差）<12.12%，准确度（相对回收率）范围为98.89%至104.24%。验证后的测定方法成功应用于藁本内酯I在犬体内的药代动力学和生物利用度研究。结果表明：（a）藁本内酯I在犬体内的消除半衰期较短（<1小时）；（b）其口服生物利用度>40%；（c）在1 - 50 mg/kg的剂量范围内，藁本内酯I在犬血浆中的药代动力学特征与剂量无关。
