College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116000, China.
Molecules. 2018 Dec 7;23(12):3234. doi: 10.3390/molecules23123234.
Atractylodis Rhizoma is the dried rhizome of (Thunb.) DC. or (DC.) Koidz and is often processed by stir-frying with wheat bran to reduce its dryness and increase its spleen tonifying activity. However, the mechanism by which the processing has this effect remains unknown. To explain the mechanism based on the pharmacokinetics of the active compounds, a rapid, sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was developed to analyze atractylenolides I, II, and III, and atractyloside A simultaneously in rat plasma after oral administration of raw and processed Atractylodis Rhizoma. Acetaminophen was used as the internal standard and the plasma samples were pretreated with methanol. Positive ionization mode coupled with multiple reaction monitoring mode was used to analyze the four compounds. The method validation revealed that all the calibration curves displayed good linear regression over the concentration ranges of 3.2⁻350, 4⁻500, 4⁻500, and 3.44⁻430 ng/mL for atractylenolides I, II, and III, and atractyloside A, respectively. The relative standard deviations of the intra- and inter-day precisions of the four compounds were less than 6% with accuracies (relative error) below 2.38%, and the extraction recoveries were more than 71.90 ± 4.97%. The main pharmacokinetic parameters of the four compounds were estimated with Drug and Statistics 3.0 and the integral pharmacokinetics were determined based on an area under the curve weighting method. The results showed that the integral maximum plasma concentration and area under the curve increased after oral administration of processed Atractylodis Rhizoma.
苍术为菊科植物茅苍术（Atractylodes lancea）或北苍术（Atractylodes chinensis）的干燥根茎，常麸炒炮制，以减其燥性、增强健脾作用。然而，炮制减其燥性、增强健脾作用的机制尚不清楚。为从活性成分的药代动力学角度阐释其机制，本研究建立了一种快速、灵敏的超高效液相色谱-串联质谱法，同时测定大鼠灌胃生苍术和麸炒苍术后血浆中苍术内酯 I、II、III 和苍术苷 A 的浓度。采用乙腈沉淀蛋白法处理血浆样品，以醋氨酚为内标，采用正离子多反应监测模式进行检测。方法学验证结果表明，苍术内酯 I、II、III 和苍术苷 A 的线性范围分别为 3.2⁻350、4⁻500、4⁻500 和 3.44⁻430 ng/mL，日内和日间精密度的相对标准偏差均小于 6%，准确度（相对误差）均低于 2.38%，提取回收率均大于 71.90±4.97%。采用药代动力学 3.0 软件计算各化合物的主要药代动力学参数，并采用梯形面积法计算积分药代动力学参数。结果显示，与生苍术相比，苍术经麸炒炮制后，其主要药代动力学参数的积分最大血浆浓度和曲线下面积均增加。
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