Drug metabolite heterogeneity in cultured single cells profiled by pico-trapping direct mass spectrometry

Nanomedicine
Yasufumi FukanoTsutomu Masujima

Abstract

We investigated the heterogeneity of tafluprost metabolism in primary human hepatocytes at a single-cell level by live single-cell mass spectrometry (MS). Picoliter volumes of cytoplasm were analyzed by nano-electrospray ionization MS in order to obtain single-cell metabolite profiles. The subcellular components of a single tafluprost-treated human hepatocyte were isolated and the single-cell metabolite profile was compared with those of traditional bulk hepatocyte analysis. In the bulk hepatocyte analysis, liquid chromatography-MS showed the averaged metabolism of tafluprost to tafluprost acid (TA) and β-oxidized metabolites. However, live single-cell MS showed that tafluprost metabolism varied among individual cells. In addition, there was significant variation in the quantities of TA and a major metabolite, dinor-TA, among cells, whereas there was no significant variation in 7-ethoxycoumarin metabolism. Thus, live single-cell MS successfully detected the heterogeneity of drug metabolism in individual living hepatocytes.

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Citations

Jan 5, 2014·Lab on a Chip·Mohammad Ali KhorshidiHelene Andersson Svahn
Nov 14, 2015·Analytical Chemistry·Julia Laskin, Ingela Lanekoff
Apr 1, 2017·Analytical Chemistry·Orane Guillaume-GentilJulia A Vorholt
Jul 28, 2018·Biointerphases·H Michelle GrandinFredrik Höök
Mar 15, 2018·Journal of the American Society for Mass Spectrometry·Bo YangJeremy L Norris
Jun 7, 2018·Analytical Chemistry·Ruichuan YinJulia Laskin
Sep 25, 2019·Analytical Chemistry·Tom M J EversAlireza Mashaghi
Aug 22, 2021·Journal of Pharmaceutical and Biomedical Analysis·Kenji YahataKenichiro Todoroki

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Methods Mentioned

BETA
imaging technique
imaging techniques

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