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OtherArticle

Detoxication vs. Bioactivation Pathways of Lapatinib In Vitro: UGT1A1 Catalyzes the Hepatic Glucuronidation of Debenzylated Lapatinib

Dasean T. Nardone-White, Jennifer E. Bissada, Arsany A. Abouda and Klarissa D. Jackson
Drug Metabolism and Disposition December 29, 2020, DMD-AR-2020-000236; DOI: https://doi.org/10.1124/dmd.120.000236
Dasean T. Nardone-White
1Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, United States of America
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Jennifer E. Bissada
2Department of Pharmaceutical Sciences, Lipscomb University, United States of America
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Arsany A. Abouda
2Department of Pharmaceutical Sciences, Lipscomb University, United States of America
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Klarissa D. Jackson
3Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, United States of America
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  • ORCID record for Klarissa D. Jackson
  • For correspondence: klarissa.jackson@unc.edu

Data Supplement

  • Supplemental Data  -

    Supplemental Materials and Methods

    Supplemental Table S1 - Donor information for UGT1A1-genotyped human liver microsomes.

    Supplemental Figure S1 - LC-MS/MS analysis of debenzylated lapatinib (M1) glucuronide conjugate.

    Supplemental Figure S2 - Time-course for formation of lapatinib M1 quinoneimineGSH conjugate in pooled human liver microsomes.

    Supplemental Figure S3 - LC-MS/MS analysis of M1 and d4-M1 derived quinoneimine-GSH conjugates.

    Supplemental Figure S4 - Representative LC-SRM chromatograms from analysis of M1, d4-M1, and the corresponding quinoneimine-GSH conjugates.

    Supplemental Figure S5 - Representative LC-SRM chromatograms of M1, M3, M1-sulfate, and M1-glucuronide.

    Supplemental Figure S6 - M1-glucuronide hydrolysis by treatment with bglucuronidase/arylsulfatase.

    Supplemental Figure S7 - M1-sulfate hydrolysis by treatment with bglucuronidase/arylsulfatase.

    Supplemental References

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