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Personalized monitoring of therapeutic salicylic acid in dried blood spots using a three-layer setup and desorption electrospray ionization mass spectrometry

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Abstract

Desorption electrospray ionization (DESI) mass spectrometry is an emerging technology for direct therapeutic drug monitoring in dried blood spots (DBS). Current DBS methods require manual application of small molecules as internal standards for absolute drug quantification. With industrial standardization in mind, we superseded the manual addition of standard and built a three-layer setup for robust quantification of salicylic acid directly from DBS. We combined a dioctyl sodium sulfosuccinate weave facilitating sample spreading with a cellulose layer for addition of isotope-labeled salicylic acid as internal standard and a filter paper for analysis of the standard-containing sample by DESI-MS. Using this setup, we developed a quantification method for salicylic acid from whole blood with a validated linear curve range from 10 to 2000 mg/L, a relative standard deviation (RSD%) ≤14 %, and determination coefficients of 0.997. The limit of detection (LOD) was 8 mg/L and the lower limit of quantification (LLOQ) was 10 mg/L. Recovery rates in method verification by LC-MS/MS were 97 to 101 % for blinded samples. Most importantly, a study in healthy volunteers after administration of a single dose of Aspirin provides evidence to suggest that the three-layer setup may enable individual pharmacokinetic and endpoint testing following blood collection by finger pricking by patients at home. Taken together, our data suggests that DBS-based quantification of drugs by DESI-MS on pre-manufactured three-layer cartridges may be a promising approach for future near-patient therapeutic drug monitoring.

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Acknowledgments

M.S., K.K., N.F., and V.H. are employees of Roche Diabetes Care GmbH, Mannheim. The company funded the work. The authors thank Herbert Fink for comments on the manuscript.

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Authors and Affiliations

  1. Instrumental Analysis and Bioanalysis, Department of Biotechnology, Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163, Mannheim, Germany

    Markus Siebenhaar & Carsten Hopf

  2. Institute of Medical Technology, University of Heidelberg and Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163, Mannheim, Germany

    Markus Siebenhaar & Carsten Hopf

  3. Roche Diabetes Care GmbH, Sandhofer Straße 116, 68305, Mannheim, Germany

    Markus Siebenhaar, Kai Küllmer, Nuno Miguel de Barros Fernandes & Volker Hüllen

Authors
  1. Markus Siebenhaar
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  2. Kai Küllmer
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  3. Nuno Miguel de Barros Fernandes
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  4. Volker Hüllen
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  5. Carsten Hopf
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Corresponding author

Correspondence to Carsten Hopf.

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Siebenhaar, M., Küllmer, K., de Barros Fernandes, N.M. et al. Personalized monitoring of therapeutic salicylic acid in dried blood spots using a three-layer setup and desorption electrospray ionization mass spectrometry. Anal Bioanal Chem 407, 7229–7238 (2015). https://doi.org/10.1007/s00216-015-8887-8

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  • DOI: https://doi.org/10.1007/s00216-015-8887-8

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