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