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Issue 19, 2017
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Online monitoring of hepatic rat metabolism by coupling a liver biochip and a mass spectrometer

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Abstract

A microfluidic liver biochip was coupled with a mass spectrometer to detect in real time the drug metabolism of hepatocytes. The hepatocytes were cultivated in the biochip for 35 h. The biochip was placed in a small-scale incubator in which the temperature and CO2 concentration were controlled. The biochip was connected serially to a mass spectrometer, a peristaltic pump and a culture medium reservoir. The injection in the mass spectrometer was performed every 10 min for 11 h. The metabolism of midazolam, phenacetin, omeprazole, dextromethorphan, repaglinide, rosuvastatin, tolbutamide and caffeine was investigated. We monitored the apparition of omeprazole sulfone, hydroxy omeprazole, repaglinide glucuronide, rosuvastatin lactone, dextrorphan, 1-hydroxy midazolam, 4-hydroxy midazolam, 1,4-hydroxy midazolam, paracetamol and 1,3-methylxanthine. Although these were observed, hydroxytolbutamide, 3-methoxymorphinan and midazolam glucuronide, hydroxy repaglinide were not detected. Based on a pharmacokinetic model, we calculated in vitro intrinsic clearances in which adsorption onto the perfusion circuit was taken into account. Then, using a liver organ model, we extrapolated the in vitro intrinsic clearances to the in vivo clearances. The estimated in vivo clearances were in agreement with the literature data on rats for midazolam, dextromethorphan, phenacetin, tolbutamide and caffeine. Rosuvastatin, omeprazole and repaglinide prediction underestimated the in vivo data.

Graphical abstract: Online monitoring of hepatic rat metabolism by coupling a liver biochip and a mass spectrometer

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Supplementary files

Article information


Submitted
11 Jun 2017
Accepted
17 Aug 2017
First published
23 Aug 2017

Analyst, 2017,142, 3747-3757
Article type
Paper

Online monitoring of hepatic rat metabolism by coupling a liver biochip and a mass spectrometer

F. Merlier, R. Jellali and E. Leclerc, Analyst, 2017, 142, 3747
DOI: 10.1039/C7AN00973A

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