Method development for quantification of DMET-proteins in the paediatric intestinal tract via LC-MS/MS using a QconCAT technique

Abstract

Physiologically based pharmacokinetic (PBPK) modelling is a powerful alternative for paediatric clinical trials. Paediatric PBPK models require data on intestinal drug metabolising enzymes and transporter (DMET)-protein abundances, however only limited data is available. This is the first study to report paediatric duodenal DMET protein quantification using a QconCAT approach. Thirty-six paediatric intestinal biopsies have been obtained from which the total mucosal protein was extracted. Proteins were digested to peptides using FASP and peptide levels were quantified using LC-MS/MS. Preliminary results provide some insight on the effect of age on duodenal protein abundance.

Keywords

Paediatrics, Proteomics, PBPK modelling, Biopharmaceutics

How to Cite

Goelen, J., Horniblow, R. D. & Batchelor, H., (2022) “Method development for quantification of DMET-proteins in the paediatric intestinal tract via LC-MS/MS using a QconCAT technique”, British Journal of Pharmacy 7(2). doi: https://doi.org/10.5920/bjpharm.1166

Funding

  • Certara Simcyp
331

Views

84

Downloads

Share

Authors

Jan Goelen (University of Birmingham)
Richard D Horniblow orcid logo (University of Birmingham)
Hannah Batchelor (Strathclyde)

Download

Issue

Dates

Licence

Creative Commons Attribution 4.0

Identifiers

File Checksums (MD5)

  • Full text: 0019f690a2ac50b439c0e6028ed59183