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Analytical and Bioanalytical Chemistry

, Volume 411, Issue 1, pp 181–191 | Cite as

Volumetric absorptive microsampling as an alternative sampling strategy for the determination of paracetamol in blood and cerebrospinal fluid

  • Lisa Delahaye
  • Evelyn Dhont
  • Pieter De Cock
  • Peter De Paepe
  • Christophe P. StoveEmail author
Research Paper

Abstract

In the field of bioanalysis, dried matrix spot sampling is increasingly receiving interest, as this alternative sampling strategy offers many potential benefits over traditional sampling, including matrix volume-sparing properties. By using a microsampling strategy, e.g., volumetric absorptive microsampling (VAMS), the number of samples that can be collected from a patient can be increased, as a result of the limited sample volume that is required per sample. To date, no VAMS-based methods have been developed for the quantification of analytes in cerebrospinal fluid (CSF). The objective of this study was to develop and validate two LC-MS/MS methods for the quantification of paracetamol in dried blood and dried CSF, with both matrices sampled using VAMS. Both methods were fully validated based on internationally accepted guidelines. Paracetamol was chromatographically separated from its glucuronide and sulfate metabolites and no carry-over or unacceptable interferences were detected. The total precision (%RSD) was below 15% for all QC levels and accuracy (%bias) was below 7% (17% for the LLOQ of aqueous VAMS). The influence of the hematocrit on the recovery of blood VAMS samples appeared to be limited within the hematocrit range of 0.21 to 0.62. The blood VAMS samples were stable for 1 week if stored at 50 °C, and for at least 8 months when stored between − 80 °C and room temperature. The aqueous VAMS samples were stable for at least 9 months when stored between − 80 and 4 °C, and for 1 month when stored at room temperature. Application of the methods on external quality control material and analysis of patient samples demonstrated the validity and utility of the methods and provided a proof of concept for the analysis of CSF microsamples obtained via VAMS devices.

Graphical abstract

Keywords

Volumetric absorptive microsampling Liquid chromatography-tandem mass spectrometry Alternative sampling strategies Cerebrospinal fluid Paracetamol 

Abbreviations

ANOVA

Analysis of variance

CSF

Cerebrospinal fluid

DMS

Dried matrix spot

EMA

European Medicines Agency

EQC

External quality control

ESI

Electrospray ionization

FA

Formic acid

FDA

US Food and Drug Administration

Hct

Hematocrit

IS

Internal standard

LC

Liquid chromatography

LLOQ

Lower limit of quantification

ME

Matrix effect

MRM

Multiple reaction monitoring

MS/MS

Tandem mass spectrometry

QC

Quality control

RSD

Relative standard deviation

ULOQ

Upper limit of quantification

VAMS

Volumetric absorptive microsampling

Notes

Acknowledgements

The authors wish to acknowledge Prof. Veronique Stove and her team for assistance with blood collection and hematocrit measurements and all volunteers who participated in the study.

Funding information

This study was supported by the Research Foundation – Flanders (G0E010916N).

Compliance with ethical standards

Approval for the clinical proof-of-concept part of this study was provided by the Ethics Committee of Ghent University Hospital (B670201629325). Informed consent has been obtained from the participants involved or their legal representatives.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2018_1427_MOESM1_ESM.pdf (672 kb)
ESM 1 (pdf 671 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Lisa Delahaye
    • 1
  • Evelyn Dhont
    • 2
    • 3
  • Pieter De Cock
    • 2
    • 3
    • 4
  • Peter De Paepe
    • 3
    • 5
  • Christophe P. Stove
    • 1
    Email author
  1. 1.Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical SciencesGhent UniversityGhentBelgium
  2. 2.Department of Pediatric Intensive CareGhent University HospitalGhentBelgium
  3. 3.Heymans Institute of PharmacologyGhent UniversityGhentBelgium
  4. 4.Department of PharmacyGhent University HospitalGhentBelgium
  5. 5.Department of Emergency MedicineGhent University HospitalGhentBelgium

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