Automated system for on-line desorption of dried blood spots applied to LC/MS/MS pharmacokinetic study of flurbiprofen and its metabolite

Unit of Toxicology, University Center of Legal Medicine, Geneva, Switzerland
Journal of pharmaceutical and biomedical analysis (Impact Factor: 2.98). 01/2011; 54(2):359-67. DOI: 10.1016/j.jpba.2010.08.032
Source: PubMed


This paper illustrates the development of an automated system for the on-line bioanalysis of dried blood spots (on-line DBS). In this way, a prototype was designed for integration into a conventional LC/MS/MS, allowing the successive extraction of 30 DBS toward the analytical system without any sample pretreatment. The developed method was assessed for the DBS analysis of flurbiprofen (FLB) and its metabolite 4-hydroxyflurbiprofen (OH-FLB) in human whole blood (i.e. 5 μL). The automated procedure was fully validated based on international criteria and showed good precision, trueness, and linearity over the expected concentration range (from 10 to 1000 ng/mL and 100 to 10,000 ng/mL for OH-FLB and FLB respectively). Furthermore, the prototype showed good results in terms of recovery and carry-over. Stability of both analytes on filter paper was also investigated and the results suggested that DBS could be stored at ambient temperature for over 1 month. The on-line DBS automated system was then successfully applied to a pharmacokinetic study performed on healthy male volunteers after oral administration of a single 50-mg dose of FLB. Additionally, a comparison between finger capillary DBS and classic venous plasma concentrations was investigated. A good correlation was observed, demonstrating the complementarity of both sampling forms. The automated system described in this article represents an efficient tool for the LC/MS/MS analysis of DBS samples in many bioanalytical applications.

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    • "Previously, an online extraction procedure using an inox cell or an autosampler was proposed for DBS extrac- tion. [43] [44] Offline extraction procedures described previously were known to involve the extraction of DBS paper with solvent , followed by centrifugation and then injection into the LC/MS/MS system. [37] [45] In "
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    • "Currently, major efforts are also being undertaken to render DBS analysis high-throughput-capable. Examples include the automated analysis of DBS, the on-line extraction and analysis of DBS ('direct elution') and direct desorption of DBS (e.g. Crawford et al., 2011, Déglon et al., 2011a). These new developments have recently been reviewed elsewhere (Déglon et al., 2011b, Abu-Rabie, 2011). "
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