Automated system for on-line desorption of dried blood spots applied to LC/MS/MS pharmacokinetic study of flurbiprofen and its metabolite.
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.
Déglon
Julien
J
Unit of Toxicology, University Center of Legal Medicine, Geneva, Switzerland; Swiss Centre for Applied Human Toxicology, University of Geneva, Geneva, Switzerland.
Thomas
Aurélien
A
Daali
Youssef
Y
Lauer
Estelle
E
Samer
Caroline
C
Desmeules
Jules
J
Dayer
Pierre
P
Mangin
Patrice
P
Staub
Christian
C
D000284:Administration, Oral; D000327:Adsorption; D001774:Blood Chemical Analysis / Q000379:methods*; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods; D003890:Desiccation; D004355:Drug Stability; D004356:Drug Storage; D005480:Flurbiprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017408:Guidelines as Topic; D006801:Humans; D008297:Male; D008851:Micropore Filters; D009862:Online Systems; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D013048:Specimen Handling / Q000379:methods; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000379:methods*
D013607:Tablets; D005480:Flurbiprofen