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

Zhang, X ; Sharif University of Technology | 2007

618 Viewed
  1. Type of Document: Article
  2. DOI: 10.1021/ac070177c
  3. Publisher: 2007
  4. Abstract:
  5. An integrated microsampling approach based on solid-phase microextraction (SPME) was developed to provide a complete solution to highly efficient and accurate pharmacokinetic studies. The microsampling system included SPME probes that are made of poly(ethylene glycol) (PEG) and C18-bonded silica, a fast and efficient sampling strategy with accurate kinetic calibration, and a high-throughput desorption device based on a modified 96-well plate. The sampling system greatly improved the quantitative capability of SPME in two ways. First, the use of the C18-bonded silica/PEG fibers minimized the competition effect from analogues of the target analytes in a complicated sample matrix such as blood or plasma samples, which is a common problem associated with solid coating SPME fibers for quantitative analysis. Moreover, the C18-bonded silica/PEG fibers provide high sensitivity and a large dynamic range that covers the possible sample concentration range during diazepam administration and elimination. Second, the kinetic calibration method offers more accurate quantitation than the calibration curve method for in vivo SPME, because it compensates for convection and matrix effects during sampling. Therefore, it is especially suitable as a fast sampling technique for pre-equilibrium SPME. Furthermore, with the high-throughput desorption device, the integrated system offers compactness and high efficiency. Its feasibility for in vivo sampling was demonstrated by monitoring diazepam pharmacokinetics and validated by conventional chemical assays and equilibrium SPME. In addition, we propose a simple method to determine the aparent distribution constant between an SPME fiber and a blood matix (Kfs) and the distribution constant between an SPME fiber and a pure PBS buffer sample matrix (K fb). As a result, both total and free concentrations of the drug and its metabolites can be detected simultaneously. Accordingly, the binding constants to the blood matrix can be obtained, which are of special significance for clinical diagnosis and drug discovery. © 2007 American Chemical Society
  6. Keywords:
  7. Desorption ; Extraction ; Kinetics ; Metabolites ; Polyethylene glycols ; Sensitivity analysis ; Silica ; Chemical assays ; Microsampling ; Solid coatings ; Solid phase microextraction ; Pharmacokinetics ; Carbon ; Diazepam ; Drug metabolite ; Macrogol ; Nordazepam ; Oxazepam ; Silicon dioxide ; Accuracy ; Animal experiment ; Animal tissue ; Binding affinity ; Blood sampling ; Controlled study ; Device ; Dog ; Drug distribution ; Drug elimination ; Feasibility study ; High throughput screening ; Nonhuman ; Plasma ; Quantitative analysis ; Quantitative assay ; Sampling ; Validation process ; Blood ; Calibration ; Laboratory Techniques and Procedures ; Nanotechnology ; Reproducibility of Results ; Sensitivity and Specificity ; Silanes
  8. Source: Analytical Chemistry ; Volume 79, Issue 12 , 2007 , Pages 4507-4513 ; 00032700 (ISSN)
  9. URL: https://pubs.acs.org/doi/10.1021/ac070177c