On-line desorption of dried blood spots coupled to hydrophilic interaction/reversed-phase LC/MS/MS system for the simultaneous analysis of drugs and their polar metabolites

Authors

  • Aurélien Thomas,

    1. Unit of Toxicology, University Center of Legal Medicine, Geneva, Switzerland
    2. Swiss Center of Applied Human Toxicology, University of Geneva, Geneva, Switzerland
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    • These two authors contributed equally to this work.

  • Julien Déglon,

    1. Unit of Toxicology, University Center of Legal Medicine, Geneva, Switzerland
    2. Swiss Center of Applied Human Toxicology, University of Geneva, Geneva, Switzerland
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    • These two authors contributed equally to this work.

  • Thierry Steimer,

    1. Unit of Clinical Psychopharmacology, Geneva University Hospitals, Geneva, Switzerland
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  • Patrice Mangin,

    1. Unit of Toxicology, University Center of Legal Medicine, Geneva, Switzerland
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  • Youssef Daali,

    1. Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland
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  • Christian Staub

    Corresponding author
    1. Unit of Toxicology, University Center of Legal Medicine, Geneva, Switzerland
    2. Swiss Center of Applied Human Toxicology, University of Geneva, Geneva, Switzerland
    • Unit of Toxicology, University Center of Legal Medicine, 1 rue Michel Servet, 1211 Genève 4, Switzerland Fax:+41-22-7892417
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Abstract

An assay for the simultaneous analysis of pharmaceutical compounds and their metabolites from micro-whole blood samples (i.e. 5 μL) was developed using an on-line dried blood spot (on-line DBS) device coupled with hydrophilic interaction/reversed-phase (HILIC/RP) LC/MS/MS. Filter paper is directly integrated to the LC device using a homemade inox desorption cell. Without any sample pretreatment, analytes are desorbed from the paper towards an automated system of valves linking a zwitterionic-HILIC column to an RP C18 column. In the same run, the polar fraction is separated by the zwitterionic-HILIC column while the non-polar fraction is eluted on the RP C18. Both fractions are detected by IT-MS operating in full scan mode for the survey scan and in product ion mode for the dependant scan using an ESI source. The procedure was evaluated by the simultaneous qualitative analysis of four probes and their relative phase I and II metabolites spiked in whole blood. In addition, the method was successfully applied to the in vivo monitoring of buprenorphine metabolism after the administration of an intraperitoneal injection of 30 mg/kg on adult female Wistar rat.

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