Received on December 2, 2005
Accepted on January 30, 2006

Automation and Analytical Techniques

Fast In Vivo Microextraction: A New Tool for Clinical Analysis

¹ Department of Chemistry, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada

^* To whom correspondence should be addressed. E-mail: janusz{at}uwaterloo.ca.

Background: We sought to develop a technique with the potential to partly replace current methods of analysis based on blood draws. To achieve this goal, we developed an in vivo microextraction technique that is faster than conventional methods, interferes minimally with the investigated system, minimizes errors associated with sample preparation, and limits exposure to hazardous biological samples.

Methods: Solid-phase microextraction devices based on hydrophilic polypyrrole and polyethyleneglycol coatings were used for direct extraction of drugs from the flowing blood of beagle dogs, over a period of 8 h. The drugs extracted on the probes were subsequently quantified by liquid chromatography coupled to tandem mass spectrometry. Two calibration strategies--external and standard on the fiber--were used to correlate the amount extracted with the in vivo concentration.

Results: Diazepam and its metabolites were successfully monitored over the course of a pharmacokinetic study, repeated 3 times on 3 beagles. The fast microextraction technique was validated by comparison with conventional plasma analysis, and a correlation factor of 0.99 was obtained. In addition to total concentrations, the method was useful for determining free drug concentrations.

Conclusions: The proposed technique has several advantages and is suitable for fast clinical analyses. This approach could be used not only for drugs, but for any other endogenous or exogenous compounds.