关键词: LC–MS/MS method Xiakucao Oral liquid pharmacokinetic rat plasma

Mesh : Animals Tandem Mass Spectrometry / methods Rats Drugs, Chinese Herbal / pharmacokinetics chemistry administration & dosage Reproducibility of Results Rats, Sprague-Dawley Linear Models Chromatography, Liquid / methods Limit of Detection Male Liquid-Liquid Extraction / methods Sensitivity and Specificity

来  源:   DOI:10.1002/bmc.5902

Abstract:
Xiakucao Oral Liquid (XKCOL) has been widely used for treating mammary gland hyperplasia and goiter in China. However, its pharmacokinetic data have been missing to date. To conduct its pharmacokinetic study, we established an LC-tandem mass spectrometry method for the simultaneous determination of eight XKCOL-related compounds in rat plasma. Liquid-liquid extraction was used for the sampling process. Chromatographic separation was performed on a Phenomenon Luna C18 column with a mobile phase of methanol and 2 mM ammonium acetate, using gradient elution at a flow rate of 0.8 mL/min. Detection was performed in the multiple reaction monitoring mode using negative electrospray ionization (ESI-) with optimized MS parameters. Endogenous substances and carryover did not interfere in the detection of analytes. The calibration curves showed a good linear relationship within the linear ranges. The intra- and inter-batch accuracy and precision were 94.8%-110.0% and ≤11.2%, respectively. There was no significant matrix effect and the recovery was reproducible. The dilution of samples did not affect the accuracy and precision. The solution and plasma samples were stable under the various test conditions. The major components of XKCOL absorbed into the blood were salvianic acid A and rosmarinic acid. They demonstrated linear kinetics over the dose range used in this study.
摘要:
夏枯草口服液(XKCOL)在中国已被广泛用于治疗乳腺增生和甲状腺肿。然而,迄今为止,其药代动力学数据一直缺失。为了进行药代动力学研究,我们建立了同时测定大鼠血浆中8种XKCOL相关化合物的LC-串联质谱方法。采样过程使用液-液萃取。色谱分离是在现象LunaC18柱上进行的,流动相为甲醇和2mM乙酸铵,使用梯度洗脱,流速为0.8mL/min。使用具有优化的MS参数的负电喷雾电离(ESI-)以多反应监测模式进行检测。内源性物质和残留不会干扰分析物的检测。校准曲线在线性范围内显示出良好的线性关系。批内和批间准确度和精密度分别为94.8%-110.0%和≤11.2%,分别。没有明显的基体效应,回收率是可重复的。样品的稀释不影响准确度和精密度。溶液和血浆样品在各种测试条件下是稳定的。XKCOL吸收到血液中的主要成分是丹参酸A和迷迭香酸。他们证明了在本研究中使用的剂量范围内的线性动力学。
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