LC-MS/MS-based method for simultaneous quantification of known chemicals and metabolites of Alpiniae oxyphyllae Fructus extract in rat plasma and its application in a pharmacokinetic study

Analytical Methods

Xu-Guang Zhang³  Zhen-Miao Qin¹  Yin-Feng Tan¹  Feng Chen¹  Wei Li²  Qi Wen³  Hai-Long Li¹  Yong-Hui Li¹  Jun-Qing Zhang¹ 

[1] Department of Pharmacy, Hainan Medical College,Haikou 571199,ChinaHainan Provincial Key Laboratory of R&D of Tropical Herbs, Hainan Medical College,Haikou 571199,ChinaDepartment of Pharmacy, Hainan Medical College,Haikou 571199,ChinaDepartment of Pharmacy, Hainan Medical College,Haikou 571199,ChinaHainan Provincial Key Laboratory of R&D of Tropical Herbs, Hainan Medical College,Haikou 571199,ChinaHainan Provincial Key Laboratory of R&D of Tropical Herbs, Hainan Medical College,Haikou 571199,ChinaDepartment of Pharmacy, Hainan Medical College,Haikou 571199,ChinaHainan Provincial Key Laboratory of R&D of Tropical Herbs, Hainan Medical College,Haikou 571199,China;Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College,Haikou 571199,ChinaHainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College,Haikou 571199,ChinaHainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College,Haikou 571199,China;Department of Pharmacy, Hainan Medical College,Haikou 571199,ChinaDepartment of Pharmacy, Hainan Medical College,Haikou 571199,ChinaDepartment of Pharmacy, Hainan Medical College,Haikou 571199,China

DOI  :  10.1039/C5AY03389F

学科分类：分析化学

来源: Royal Society of Chemistry

【 摘 要 】

Alpiniae oxyphyllae Fructus (Yizhi in Chinese) is commonly used for the treatment of diarrhea, intestinal disorders and urinary incontinence symptoms. To date, little information is available on the pharmacokinetic (PK) properties of this herb. We have identified the known active chemicals (including nootkatone, yakuchinone A, yakuchinone B, oxyphyllacinol, tectochrysin, chrysin, izalpinin, apigenin-4′,7-dimethylether, and kaempferide) and their metabolites (phase II metabolites and oxidized product such as kaempferol) from Yizhi extract in rat plasma using liquid chromatography/tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring. In the present study, an LC-MS/MS-based method was developed and validated for the simultaneous quantitation of the Yizhi chemicals and their metabolites in rat plasma after enzymatic treatment. A mixture of β-glucuronidase and sulfatase was used to liberate parent chemicals from their phase II metabolites. A post-extraction spike method, as well as a post-column infusion method, was conducted to investigate matrix-effects. Particularly, the ion suppression effect for all the analytes was overcome through combining a liquid–liquid extraction method for clean-up, elution gradient optimization for separation and inclusion of very low concentration of HCOOH into the mobile phase. Mean accuracies were obtained in the range of 84.7–112% at three different quality control levels for the ten analytes, with intra- and inter-day variations within 13.6% (1.76–13.6%). This validated method was successfully applied to a PK investigation in rats after a single oral administration of Yizhi extract. These results supply a suitable reference for further PK studies of the Yizhi chemicals and their metabolites in the future.

【 授权许可】

Unknown