Off-line two-dimensional liquid chromatography coupled with diode array detection and quadrupole-time of flight mass spectrometry for the biotransformation kinetics of Ginkgo biloba leaves extract by diabetic rat liver microsomes.

Autor: Zheng XX; Department of Pharmacy, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou 221002, China; Key Laboratory of New Drug Research and Clinical Pharmacy of Jiangsu Province, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China., Du Y; Key Laboratory of New Drug Research and Clinical Pharmacy of Jiangsu Province, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China., Xu BJ; Key Laboratory of New Drug Research and Clinical Pharmacy of Jiangsu Province, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China., Wang TY; Key Laboratory of New Drug Research and Clinical Pharmacy of Jiangsu Province, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China., Zhong QQ; Key Laboratory of New Drug Research and Clinical Pharmacy of Jiangsu Province, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China., Li Z; Key Laboratory of New Drug Research and Clinical Pharmacy of Jiangsu Province, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China., Ji S; Key Laboratory of New Drug Research and Clinical Pharmacy of Jiangsu Province, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China., Guo MZ; Key Laboratory of New Drug Research and Clinical Pharmacy of Jiangsu Province, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China., Yang DZ; Key Laboratory of New Drug Research and Clinical Pharmacy of Jiangsu Province, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China., Tang DQ; Key Laboratory of New Drug Research and Clinical Pharmacy of Jiangsu Province, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China. Electronic address: tangdq@xzhmu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2019 Mar 01; Vol. 1109, pp. 1-9. Date of Electronic Publication: 2019 Jan 23.
DOI: 10.1016/j.jchromb.2019.01.015
Abstrakt: Ginkgo biloba leaves extract (GBE), one of the most widely used traditional Chinese medicines worldwide, can be used for the treatment of diabetes mellitus (DM). However, its biotransformation in liver is not fully known under the state of DM. In this study, an off-line hydrophilic interaction × reversed-phase two-dimensional liquid chromatography (HILIC × RP 2D-LC) system coupled with diode array detection (DAD) and quadrupole time-of-flight mass spectrometry (q/TOF-MS) was established for the qualification and quantification of the biotransformation of GBE in normal and diabetic rat liver microsomes (RLMs). 6 metabolites were tentatively identified according to the exact molecular weights and the characteristic fragment ions provided by q/TOF-MS data. The results of metabolic stability showed that the metabolic ratio of four target compounds including quercetin, genistein, kaempferol and isorhamnetin in diabetic RLMs were significantly enhanced when comparing with normal RLMs. The results of enzyme kinetics showed that compared with normal RLMs, the Michaelis-Menten constant (K m ) value of genistein was obvious increased while its maximal velocity (V max ) and intrinsic clearance (CL int ) values were significantly decreased by diabetic RLMs, and the V max and CL int values of kaempferol and isorhamnetin were notably enhanced while their K m values were markedly reduced. For the half-time (t 1/2 ) values of four target compounds and the K m , V max and CL int values of quercetin, there were not statistically significant changes between normal and diabetic RLMs. The results suggest that the developed off-line 2D LC-DAD-q/TOF-MS method is an easy and accurate approach for the study of GBE biotransformation in RLMs and may provide the essential data for further pharmacological and clinical studies of GBE.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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