title: In vivo solid-phase microextraction for monitoring intravenous concentrations of drugs and metabolites.
abstract: This protocol for in vivo solid-phase microextraction (SPME) can be used to monitor and quantify intravenous concentrations of drugs and metabolites without the need to withdraw a blood sample for analysis. The SPME probe is inserted directly into a peripheral vein of a living animal through a standard medical catheter, and extraction occurs typically over 2-5 min. After extraction, the analytes are removed from the sorbent and analyzed by, for example, liquid chromatography-tandem mass spectrometry. It has been validated in comparison with conventional blood analysis, and we describe here the in vitro experiments typically conducted during method development. The new-generation biocompatible SPME probes are designed specifically for extraction of semi-volatiles and nonvolatiles directly from aqueous samples and can be steam sterilized. Sorbents are coated on fine-gauge surgical steel wire (200-μm diameter), which is more rugged and biocompatible than conventional fibers (100-μm fused silica fiber). They incorporate a binding agent that resists fouling by the biological matrix and does not cause an immune response in the experimental animal. The sorbents used (coating thickness of ∼50 μm) are selected for their affinity for the types of small molecules of interest. The procedure is illustrated by the analysis of benzodiazepines with polypyrrole-coated wires inserted into peripheral blood vessels of beagles, although it can be adapted for use in smaller animals. The in vivo sampling can require as little as 1 min, in which case the entire procedure from sampling to instrumental analysis can take as little as 30 min.
authors.affiliation: Department of Chemistry, University of Waterloo, Ontario, Canada.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Lord
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: F Marcel
authors.initials: FM
authors.lastname: Musteata
authors.forename: Dajana
authors.initials: D
authors.lastname: Vuckovic
authors.forename: Janusz
authors.initials: J
authors.lastname: Pawliszyn
mesh_terms: D000327:Adsorption; D000818:Animals; D001569:Benzodiazepines / Q000097:blood / Q000737:chemistry; D001774:Blood Chemical Analysis / Q000295:instrumentation / Q000379:methods; D002138:Calibration; D020099:Coated Materials, Biocompatible; D004285:Dogs; D004364:Pharmaceutical Preparations / Q000097:blood*; D011108:Polymers / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry; D052617:Solid Phase Microextraction / Q000295:instrumentation / Q000379:methods*
chemical_list: D020099:Coated Materials, Biocompatible; D004364:Pharmaceutical Preparations; D011108:Polymers; D011758:Pyrroles; D001569:Benzodiazepines; C067635:polypyrrole