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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

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Published on: December 3, 2020

Quantitative in vivo microsampling for pharmacokinetic studies based on an integrated solid-phase microextraction

Xu Zhang¹, Ali Es-haghi, Florin Marcel Musteata

¹Department of Chemistry, University of Waterloo, Ontario, N2L 3G1, Canada.

Analytical Chemistry

|May 19, 2007

Summary

This study introduces an integrated microsampling system using solid-phase microextraction (SPME) for efficient pharmacokinetic analysis. The novel approach enhances accuracy and enables simultaneous detection of free and bound drug concentrations.

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Published on: June 21, 2019

Area of Science:

Analytical Chemistry
Pharmacokinetics
Biomedical Engineering

Background:

Pharmacokinetic studies require accurate quantification of drugs in biological matrices.
Traditional methods can be time-consuming and may not fully account for matrix effects.
Solid-phase microextraction (SPME) offers a potential alternative for simplified sample analysis.

Purpose of the Study:

To develop an integrated microsampling approach for highly efficient and accurate pharmacokinetic studies.
To improve the quantitative capabilities of SPME in complex biological samples.
To enable simultaneous determination of total and free drug concentrations.

Main Methods:

Development of SPME probes using poly(ethylene glycol) (PEG) and C18-bonded silica.
Implementation of a kinetic calibration method for accurate in vivo quantitation.
Utilization of a high-throughput desorption device for rapid sample processing.
Determination of distribution constants (Kfs and Kfb) for drug-matrix binding analysis.

Main Results:

The C18-bonded silica/PEG fibers minimized matrix competition and enhanced sensitivity and dynamic range.
Kinetic calibration provided more accurate quantitation, especially for pre-equilibrium SPME.
The integrated system demonstrated feasibility for in vivo diazepam pharmacokinetics monitoring.
Simultaneous detection of total and free drug concentrations and binding constants was achieved.

Conclusions:

The integrated SPME microsampling system offers a complete solution for efficient and accurate pharmacokinetic studies.
The method allows for simultaneous determination of free and total drug concentrations, providing valuable insights into drug-matrix binding.
This approach holds significant potential for clinical diagnosis and drug discovery.