An in vitro liver model on microfluidic device for analysis of capecitabine metabolite using mass spectrometer as detector.

Abstract

In this work, an in vitro liver model in a microfluidic device to imitate and detect prodrug metabolism was developed. A widely used prodrug capecitabine (CAP), which needs to be metabolized into active intermediate in the liver and then transformed into final effective drug in tumor cells, was selected as a model compound. The microfluidic device we exploited consists of a cell co-culture section, in which HepG2 cells were cultured to represent liver while MCF-7 cells were used to represent the tumor tissue, and an on-line solid phase extraction (SPE) section connecting to the ionization source of the ESI-Q-TOF mass spectrometer. The prodrug metabolism was realized and confirmed within this in vitro liver model as the intermediate product of the prodrug 5'-deoxy-5-fluorouridine (DFUR) was successfully detected with MS after the conditioning of HepG2 cells, and the anti-tumor effect of the active metabolite was observed through cell vitality assays of MCF-7 cells. The limit of detection (LOD) using on-chip SPE was at 10nM and semi-quantitative analysis could be realized. This system has been proved useful and practical, showing a potential to replace conventional drug screening methods.

• Authors: Jie Zhang, Jing Wu, Haifang Li, Qiushui Chen, Jin-Ming Lin
• Journal: Biosensors & bioelectronics (Biosens Bioelectron) Vol. 68 Pg. 322-328 (Jun 15 2015) ISSN: 1873-4235 [Electronic] England
• PMID: 25599844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antimetabolites, Antineoplastic
• Prodrugs
• Floxuridine
• Capecitabine
• doxifluridine

Topics

• Antimetabolites, Antineoplastic (analysis, metabolism, pharmacology)
• Biosensing Techniques (instrumentation)
• Capecitabine (analysis, metabolism, pharmacology)
• Cell Survival (drug effects)
• Coculture Techniques (instrumentation)
• Equipment Design
• Floxuridine (analysis, metabolism, pharmacology)
• Hep G2 Cells
• Humans
• Lab-On-A-Chip Devices
• Liver (metabolism)
• MCF-7 Cells
• Prodrugs (analysis, metabolism, pharmacology)
• Solid Phase Extraction (instrumentation)
• Spectrometry, Mass, Electrospray Ionization (instrumentation)