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Development and characterization of a small electromembrane extraction probe coupled with mass spectrometry for real-time and online monitoring of in vitro drug metabolism

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Abstract

A small and very simple electromembrane extraction probe (EME-probe) was developed and coupled directly to electrospray ionization mass spectrometry (ESI-MS), and this system was used to monitor in real time in vitro metabolism by rat liver microsomes of drug substances from a small reaction (incubation) chamber (37 °C). The drug-related substances were continuously extracted from the 1.0 mL metabolic reaction mixture and into the EME-probe by an electrical potential of 2.5 V. The extraction probe consisted of a 1-mm long and 350-μm ID thin supported liquid membrane (SLM) of 2-nitrophenyl octyl ether. The drugs and formed metabolites where extracted through the SLM and directly into a 3 μL min−1 flow of 60 mM HCOOH inside the probe serving as the acceptor solution. The acceptor solution was directed into the ESI-MS-system, and the MS continuously monitored the drug-related substances extracted by the EME-probe. The extraction efficiency of the EME-probe was dependant on the applied electrical potential and the length of the SLM, and these parameters as well as the volume of the reaction chamber were set to the values mentioned above to avoid serious depletion from the reaction chamber (soft extraction). Soft extraction was mandatory in order not to affect the reaction kinetics by sample composition changes induced by the EME-probe. The EME-probe/MS-system was used to establish kinetic profiles for the in vitro metabolism of promethazine, amitriptyline and imipramine as model substances.

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Acknowledgments

Bin Li and Dr. María D. Ramos Payán are acknowledged for their technical help during this project.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Helene Bonkerud Dugstad, Nickolaj Jacob Petersen, Henrik Jensen, Charlotte Gabel-Jensen, Steen Honoré Hansen & Stig Pedersen-Bjergaard

  2. School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316, Oslo, Norway

    Helene Bonkerud Dugstad & Stig Pedersen-Bjergaard

Authors
  1. Helene Bonkerud Dugstad
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  2. Nickolaj Jacob Petersen
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  3. Henrik Jensen
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  4. Charlotte Gabel-Jensen
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  5. Steen Honoré Hansen
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  6. Stig Pedersen-Bjergaard
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Corresponding author

Correspondence to Nickolaj Jacob Petersen.

Additional information

Published in the topical collection Challenges and New Directions in Analytical Sample Preparation with guest editors Astrid Gjelstad and Stig Pedersen-Bjergaard.

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Dugstad, H.B., Petersen, N.J., Jensen, H. et al. Development and characterization of a small electromembrane extraction probe coupled with mass spectrometry for real-time and online monitoring of in vitro drug metabolism. Anal Bioanal Chem 406, 421–429 (2014). https://doi.org/10.1007/s00216-013-7378-z

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  • DOI: https://doi.org/10.1007/s00216-013-7378-z

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