title: 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.affiliation: Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, The Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, The Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, The Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.
authors.forename: Haifang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, The Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.
authors.forename: Qiushui
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, The Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China. Electronic address: jmlin@mail.tsinghua.edu.cn.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Lin
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D015374:Biosensing Techniques / Q000295:instrumentation*; D000069287:Capecitabine / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques / Q000295:instrumentation; D004867:Equipment Design; D005467:Floxuridine / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008099:Liver / Q000378:metabolism*; D061986:MCF-7 Cells; D011355:Prodrugs / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D052616:Solid Phase Extraction / Q000295:instrumentation; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation
chemical_list: D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D005467:Floxuridine; D000069287:Capecitabine; C025034:doxifluridine
keywords: Capecitabine; Cell co-culture; Hepatic metabolism; MS detection; Microchip