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Dried blood spot on-card derivatization: an alternative form of sample handling to overcome the instability of thiorphan in biological matrix

Authors :
Fabio Garofolo
Jean-Nicholas Mess
Cynthia Côté
Marie-Pierre Taillon
Source :
Biomedical Chromatography. 26:1617-1624
Publication Year :
2012
Publisher :
Wiley, 2012.

Abstract

Thiorphan, the active metabolite of racecadotril, can undergo oxidation in biological matrices such as blood and plasma. In bioanalysis, a general approach for the stabilization of such a molecule is to derivatize the thiol group to a more stable thioether, often requiring complex handling procedures at the clinical site. In this research, the concept of dried blood spot (DBS) on-card derivatization was evaluated to stabilize thiorphan. DBS cards were in-house pre-treated with 2-bromo-3′-methoxyacetophenone and left to dry prior to blood spotting. Thiorphan was shown to be effectively derivatized to thiorphan–methoxyacetophenone once applied on the in-house pre-treated cards. Thiorphan–methoxyacetophenone was extracted by soaking a 6 mm DBS punch in methanol containing the internal standard (thiorphan–methoxyacetophenone-D5). Chromatographic separation was achieved on a Waters XBridge C18 column with a gradient elution of 5 m m NH4HCO3 and methanol in 2.5 min and detection by ESI(+)/MS/MS. A linear (weighted 1/x2) relationship was obtained over a concentration range of 5.00–600.00 ng/mL. The assay met regulatory guidelines acceptance criteria for sensitivity, selectivity, precision and accuracy, matrix effect, recovery, dilution integrity and multiple stability evaluations. The DBS on-card derivatization has shown to be an easy and reliable alternative form of sample collection for the quantification of thiorphan. Copyright © 2012 John Wiley & Sons, Ltd.

Details

ISSN :
02693879
Volume :
26
Database :
OpenAIRE
Journal :
Biomedical Chromatography
Accession number :
edsair.doi...........a1083091d7565e38bae5497ccc08bb30
Full Text :
https://doi.org/10.1002/bmc.2745