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Updated: Jul 6, 2026
18:57
Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
[Progress of drug transport study based on absolute quantitative method for membrane transporter proteins]
1Graduate School of Pharmaceutical Sciences, Tohoku University, SORST.JST, Aoba, Aramaki, Aoba-ku, Sendai, Japan. kamiie@azabu-u.ac.jp
Summary
Researchers developed a sensitive method to quantify membrane transporter proteins in human tissues. This advancement aids in predicting drug behavior in the body, crucial for drug discovery.
Area of Science:
- Proteomics
- Analytical Chemistry
Context:
- Accurate prediction of human pharmacokinetic profiles relies on quantifying membrane transporter expression.
- Membrane proteins, particularly high molecular-weight ones, present significant challenges in dissolution and analysis.
Purpose:
- To develop a simultaneous, highly sensitive method for absolute quantification of multiple membrane transporter proteins in mammalian tissues.
- To overcome challenges in analyzing difficult-to-dissolve membrane proteins using proteomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Summary:
- The method utilizes tryptic peptides, which are soluble and analyzable by LC-MS/MS, addressing the insolubility of membrane proteins.
- Multiple reaction monitoring (MRM) mode in LC-MS/MS enhances sensitivity and selectivity for low-expression transporter proteins by separating them from abundant molecules.
- Peptide probe selection criteria, including informatics-based filtering for stability and domain characteristics, ensure highly sensitive and specific analysis.
Impact:
- Establishes a comprehensive assay platform for quantifying all transporter proteins in animal and human tissues.
- Significantly contributes to advancing drug discovery and development through improved pharmacokinetic predictions.
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