School of Pharmacy, Shenyang Pharmaceutical University, Benxi, 117004, China.
School of Pharmacy, Shenyang Pharmaceutical University, Benxi, 117004, China.
J Pharm Biomed Anal. 2021 May 30;199:114054. doi: 10.1016/j.jpba.2021.114054. Epub 2021 Mar 31.
Using green and high efficient solvents to extract and trace active ingredients of traditional Chinese medicine (TCM) in the complex biological samples was still challenging. In this paper, a co-friendly, fast pretreatment method with high extraction efficiency, based on the tailor-made deep eutectic solvent (DES) system, combined with ultra performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination of icarrin and icarisid II in rat plasma samples, which can be further applied to comparative pharmacokinetic studies after oral administration of Herba Epimedii and icarrin monomer in rats, respectively. PrE (l-proline: ethylene glycol = 1:4 mol/mol) and acetonitrile were optimized and combined as the tailor-made DES at the volumetric ratio of 3:7 to extract icarrin and icarisid II, and to precipitate the protein in rat plasma in one step simultaneously. The extraction efficiency of the tailor-made DES was about 1.7 times of DES (PrE). The extraction recovery of icarrin and icarisid II in rat plasma samples by this method were within the range of 90-110 %, and the lower limits of quantification (LLOQ) were 0.32 ng mL (icarrin) and 0.43 ng mL (icarisid II). There was a linear relationship between 0.32-80.16 ng mL (icarrin) and 0.43-107.4 ng mL (icarisid II), which effectively reduced the detection limit. In this comparative pharmacokinetic study, the maximum plasma concentration (C) and the area under plasma concentration-time curve (AUC) of two analytes in rat plasma of Herba Epimedii group were both much higher than those in the icarrin monomer group, which suggested that other ingredients in Herba Epimedii may contribute to the in vivo absorption of icarrin and icarisid II. This simple, rapid, relatively green and high effeicient method would provide a new approach for the extraction of active ingredients from complex biological samples.
使用绿色、高效的溶剂从复杂的生物样本中提取和追踪中药（TCM）的活性成分仍然具有挑战性。本文建立了一种绿色、快速的预处理方法，该方法基于定制的深共晶溶剂（DES）体系，结合超高效液相色谱-三重四极杆串联质谱（UPLC-MS/MS），用于测定大鼠血浆样品中的淫羊藿苷和淫羊藿次苷Ⅱ。该方法可进一步应用于大鼠灌胃淫羊藿及其单体淫羊藿苷后进行比较药代动力学研究。PrE（脯氨酸：乙二醇=1:4 摩尔比）和乙腈被优化并组合成定制 DES，体积比为 3:7，用于同时一步提取大鼠血浆中的淫羊藿苷和淫羊藿次苷Ⅱ并沉淀蛋白。定制 DES 的提取效率约为 DES（PrE）的 1.7 倍。该方法测定大鼠血浆样品中淫羊藿苷和淫羊藿次苷Ⅱ的提取回收率在 90-110%范围内，定量下限（LLOQ）分别为 0.32ng/mL（淫羊藿苷）和 0.43ng/mL（淫羊藿次苷Ⅱ）。0.32-80.16ng/mL（淫羊藿苷）和 0.43-107.4ng/mL（淫羊藿次苷Ⅱ）范围内线性关系良好，有效降低了检测限。在这项比较药代动力学研究中，淫羊藿组大鼠血浆中两种分析物的最大血浆浓度（C）和血浆浓度-时间曲线下面积（AUC）均明显高于单体淫羊藿苷组，提示淫羊藿中的其他成分可能有助于淫羊藿苷和淫羊藿次苷Ⅱ的体内吸收。这种简单、快速、相对绿色、高效的方法为从复杂生物样本中提取活性成分提供了新的途径。
