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Research ArticleArticle

Direct Quantification of Cytochromes P450 and Drug Transporters - A Rapid, Targeted Mass Spectrometry-Based Immunoassay Panel for Tissues and Cell Culture Lysates

Frederik Weib, Helen Sophie Hammer, Kathrin Klein, Hannes Planatscher Planatscher, Ulrich M. Zanger, Agneta Noren, Christine Wegler, Per Artursson, Thomas O. Joos and Oliver Poetz
Drug Metabolism and Disposition January 17, 2018, dmd.117.078626; DOI: https://doi.org/10.1124/dmd.117.078626
Frederik Weib
1 SIGNATOPE GmbH;
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  • For correspondence: poetz@nmi.de weiss@signatope.com
Helen Sophie Hammer
2 SIGNATOPE GmbH, Reutlingen, Germany;
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Kathrin Klein
3 Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany;
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Hannes Planatscher Planatscher
2 SIGNATOPE GmbH, Reutlingen, Germany;
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Ulrich M. Zanger
3 Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany;
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Agneta Noren
4 Department of Surgical Sciences, Uppsala University, SE-75185 Uppsala, Sweden;
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Christine Wegler
5 Department of Pharmacy, Uppsala University, Uppsala, Sweden;
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Per Artursson
5 Department of Pharmacy, Uppsala University, Uppsala, Sweden;
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Thomas O. Joos
6 NMI Natural and Medical Sciences Institute at the University of Tubingen, Reutlingen, Germany
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Oliver Poetz
6 NMI Natural and Medical Sciences Institute at the University of Tubingen, Reutlingen, Germany
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  • For correspondence: poetz@nmi.de weiss@signatope.com

Data Supplement

  • Supplemental Data -

    Supplemental Figure 1 - Binding motifs of multi-specific TXP-antibodies

    Supplemental Figure 2 - Working range of 24 MS-based immunoassays

    Supplemental Figure 3 - Accuracy and recovery of 24 MS-based immunoassays

    Supplemental Figure 4 - Induction studies. Induction qualified human cryopreserved hepatocytes were cultivated in
    96-well plates

    Supplemental Table 1 - Correlation factors calculated from quantification results generated by measuring CYP
    enzyme and transporter concentrations from liver tissue (T) (set A), crude membrane/nuclei fraction
    (CMF) and microsomal fraction (M). Mean, CV and Pearson correlation factor are given

    Supplemental Table 2 - Quantification of CYP enzymes and transporters (technical replicates, n=3) in liver tissue (T)
    (set A), crude membrane/nuclei fraction (CMF), microsomal fraction (M), and cytosol (C) of ten liver
    samples

    Supplemental Table 3 - Interday reproducibility and variation of MS-based immunoassays of 15 human liver tissues
    (set B)


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