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采用超高效液相色谱-串联质谱法同时测定大鼠体内细辛脂素、β-桉叶醇和甘草素,并将其应用于标准品和古秘方(Gumiganghwal-tang)给药后的药代动力学研究。

Simultaneous determination of asarinin, β-eudesmol, and wogonin in rats using ultraperformance liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic studies following administration of standards and Gumiganghwal-tang.

机构信息

College of Pharmacy, Chonnam National University, Gwangju, Republic of Korea.

College of Pharmacy, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.

出版信息

Biomed Chromatogr. 2021 Apr;35(4):e5021. doi: 10.1002/bmc.5021. Epub 2020 Nov 30.

Abstract

Asarinin, β-eudesmol, and wogonin have common antiangiogenic activities and have the potential for use in chemotherapy. Besides, they are multivalent substances that are combined in various herbal medicines. The purpose of this study was to develop a method for simultaneous analysis of asarinin, β-eudesmol, and wogonin, which are representative pharmacological components of Asarum heterotropoides, Atractylodes lancea, and Scutellaria baicalensis, respectively, in rat biosamples using ultraperformance liquid chromatography-tandem mass spectrometry. The three components were separated using 5 mm aqueous ammonium acetate containing 0.1% formic acid and acetonitrile as a mobile phase, equipped with a KINETEX core-shell C column. The analysis was quantitated on a triple-quadrupole mass-spectrometer employing electrospray ionization, and operated in the multiple reaction monitoring mode. The chromatograms showed high resolution, sensitivity, and selectivity with no interference with plasma, urine, and feces constituents. The developed analytical method satisfied international guidance criteria and could be successfully applied to the pharmacokinetic (PK) studies evaluating oral bioavailability of asarinin, β-eudesmol, and wogonin after oral and intravenous administration and their urinary and fecal excretion ratios after oral administration to rats. Furthermore, the analysis was extended to PK studies following oral administration of Gumiganghwal-tang. This study was the first simultaneous analysis of the aforesaid three constituents in rat plasma, urine, and feces that also determined their PK parameters.

摘要

细辛脂素、β-桉叶醇和黄芩苷具有共同的抗血管生成活性,有可能用于化疗。此外,它们是多种物质,结合在各种草药中。本研究旨在开发一种同时分析细辛脂素、β-桉叶醇和黄芩苷的方法,这三种成分分别是细辛、白术和黄芩的代表性药理成分,在大鼠生物样品中采用超高效液相色谱-串联质谱法。使用 5mm 水相含 0.1%甲酸的乙酸铵和乙腈作为流动相,分别在 KINETEX 核壳 C 柱上分离这三种成分。分析采用电喷雾电离三重四极杆质谱仪进行定量,并采用多重反应监测模式进行操作。该色谱图具有高分辨率、灵敏度和选择性,与血浆、尿液和粪便成分无干扰。所开发的分析方法符合国际指导原则,并成功应用于口服和静脉给予后评估细辛脂素、β-桉叶醇和黄芩苷口服生物利用度及其口服给予大鼠后尿和粪排泄比的药代动力学(PK)研究。此外,该分析方法还扩展到了口服给予固元汤后的 PK 研究。本研究首次对大鼠血浆、尿液和粪便中的上述三种成分进行了同时分析,并确定了它们的 PK 参数。

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