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Scientific article
Open access
English

Liquid chromatography-high resolution mass spectrometry for broad-spectrum drug screening of dried blood spot as microsampling procedure

Published inAnalytica chimica acta, vol. 1063, p. 110-116
Publication date2019-07-31
First online date2019-02-19
Abstract

Background: Hyphenation of liquid chromatography (LC) with high-resolution mass spectrometry (HRMS) offers the potential to develop broad-spectrum screening procedures from low volumes of biological matrices. In parallel, dried blood spot (DBS) has become a valuable tool in the bioanalysis landscape to overcome conventional blood collection issues. Herein, we demonstrated the applicability of DBS as micro-sampling procedure for broad-spectrum toxicological screening.

Methods: A method was developed on a HRMS system in data dependant acquisition (DDA) mode using an extensive inclusion list to promote collection of relevant data. 104 real toxicology cases were analysed, and the results were cross-validated with one published and one commercial screening procedures. Quantitative MRM analyses were also performed on identified substances on a triple quadrupole instrument as a complementary confirmation procedure.

Results: The method showed limits of identification (LOIs) in appropriateness with therapeutic ranges for all the classes of interest. Applying the three screening approaches on 104 real cases, 271 identifications were performed including 14 and 6 classes of prescribed and illicit drugs, respectively. Among the detected substances, 23% were only detected by the proposed method. Based on confirmatory analyses, we demonstrated that the use of blood micro-samples did not impair the sensitivity allowing more identifications in the low concentration ranges.

Conclusion: A LC-HRMS assay was successfully developed for toxicological screening of blood microsamples demonstrating a high identification power at low concentration ranges. The validation procedure and the analysis of real cases demonstrated the potential of this assay by supplementing screening approaches of reference.

eng
Keywords
  • Data dependent acquisition
  • Dried blood spot
  • General unknown screening
  • High resolution mass spectrometry
  • Microsampling
  • Chromatography, Liquid
  • Dried Blood Spot Testing
  • Drug Evaluation, Preclinical / instrumentation
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Illicit Drugs / blood
  • Tandem Mass Spectrometry
Funding
  • Swiss Federal Office of Public Health - [14.013792/204.0001/-1300]
Citation (ISO format)
JOYE, Timothee et al. Liquid chromatography-high resolution mass spectrometry for broad-spectrum drug screening of dried blood spot as microsampling procedure. In: Analytica chimica acta, 2019, vol. 1063, p. 110–116. doi: 10.1016/j.aca.2019.02.011
Main files (2)
Article (Accepted version)
Article (Published version)
Identifiers
ISSN of the journal0003-2670
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87downloads

Technical informations

Creation11/19/2021 5:27:00 PM
First validation11/19/2021 5:27:00 PM
Update time03/16/2023 1:57:41 AM
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