Yang Minghan, Luo Jiaoyang, Li Kunlun, Hu Shurong, Ding Tong, Liu Hao, Sheng Ping, Yang Meihua
College of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, 830011, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 May 15;1085:30-35. doi: 10.1016/j.jchromb.2018.03.041. Epub 2018 Mar 27.
Guaiol has been used for thousands of years as a traditional Uygur medicine and is the primary active component found in Ferula ferulaeoides (Steud.) Korov (F. ferulaeoides). In our present study, a rapid, selective, and sensitive method of monitoring selected ions was established based on gas chromatography-mass spectrometry. This method was optimized for the quantification and pharmacokinetic analysis of guaiol in rat plasma following oral administration of chloroform extract from Ferula ferulaeoides. Plasma was extracted using liquid-liquid extraction with ethyl acetate and was analyzed on a HP-5MS column (30 m × 250 μm × 0.25 μm) with a mass selective detector. Detection was carried out under selected ion monitoring mode, and three selected ion monitoring ions (m/z 59.1, 107.1, and 161.1 for guaiol) were used for the quantitative determination of that under investigation. The assay demonstrated excellent linearity in the range of 1-200 ng/mL (r = 0.9993, n = 8) in the case of guaiol measured in rat plasma. The limit of detection and the limit of quantification for guaiol in rat plasma were found to be 0.25 ng/mL and 1 ng/mL, respectively. Intra-day and inter-day precisions were expressed as the relative standard deviation for the method and were in the range of 97.49%-106.16% and 97.04%-105.91%, respectively. Extraction efficiencies were all determined to be >90%, and recoveries were ranged from 91.25% to 96.24%. This method has been successfully applied for the pharmacokinetic evaluation of chloroform extract isolated from F. ferulaeoides following a single oral administration dose (157.5 mg/kg) in rats. The guaiol pharmacokinetic study demonstrated that the half-life of guaiol was 9.18 ± 3.75 h, the mean residence time was 9.07 ± 3.86 h, the maximum guaiol concentration in the plasma was 28.63 ± 6.82 ng/mL, and the maximum time guaiol was in the plasma was 0.50 h.
愈创木醇作为一种传统维吾尔药已被使用了数千年，是阿魏（新疆阿魏）中主要的活性成分。在我们目前的研究中，基于气相色谱 - 质谱联用技术建立了一种快速、选择性好且灵敏的监测选定离子的方法。该方法针对口服新疆阿魏氯仿提取物后大鼠血浆中愈创木醇的定量和药代动力学分析进行了优化。血浆采用乙酸乙酯液 - 液萃取法进行提取，并在配备质量选择性检测器的HP - 5MS柱（30 m×250 μm×0.25 μm）上进行分析。检测在选定离子监测模式下进行，使用三个选定离子监测离子（愈创木醇的m/z 59.1、107.1和161.1）对所研究的物质进行定量测定。该测定方法在大鼠血浆中愈创木醇的检测浓度范围为1 - 200 ng/mL时显示出良好的线性关系（r = 0.9993，n = 8）。大鼠血浆中愈创木醇的检测限和定量限分别为0.25 ng/mL和1 ng/mL。日内和日间精密度以该方法的相对标准偏差表示，分别在97.49% - 106.16%和97.04% - 105.91%范围内。萃取效率均测定为>90%，回收率在91.25%至96.24%之间。该方法已成功应用于大鼠单次口服给药剂量（157.5 mg/kg）后新疆阿魏氯仿提取物的药代动力学评价。愈创木醇的药代动力学研究表明，愈创木醇的半衰期为9.18±3.75 h，平均驻留时间为9.07±3.86 h，血浆中愈创木醇的最大浓度为28.63±6.82 ng/mL，愈创木醇在血浆中的最长时间为0.50 h。
