Analytical and Bioanalytical Chemistry

, Volume 409, Issue 1, pp 121–131 | Cite as

Comparison of paper spray mass spectrometry analysis of dried blood spots from devices used for in-field collection of clinical samples

  • Karen E. Yannell
  • Kristina R. Kesely
  • Huynh Dinh Chien
  • Candice B. Kissinger
  • R. Graham Cooks
Research Paper


Paper spray (PS) is an ambient ionization technique applicable to ionizing analytes from untreated dried biofluid samples. In-field sample analysis could benefit from the capability to use a finger prick of blood to measure drugs in whole blood at low cost and in a short time. Some studies may require specialized blood collection devices that can be used in remote areas. In this study, four different dried blood spot (DBS) devices are used with PS sources and tested for rapid quantification of imatinib and N-desmethyl-imatinib. A triple quadrupole mass spectrometer allows analyte detection with high sensitivity. Analytical figures of merit for the four devices are compared, and it is concluded that several of the novel devices successfully deploy DBS with PS and yield similar results to traditional manual PS methods. Clinical samples collected in a remote location were analyzed as a proof of concept for in-field blood collection and subsequent rapid laboratory analysis.

Graphical abstract

Dried blood spot analyis by paper spray ionization MS/MS for in field sample collection


Paper spray ionization Multiple reaction monitoring Therapeutic drug monitoring Field sample collection Imatinib 



The authors thank Novilytic and TomTec for supplying the blood spot devices for the study. We acknowledge funding from the National Science Foundation (CHE-1307264), the National Institutes of Health (R01 GM24417-37), and the Purdue Center for Cancer Research.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Supplementary material

216_2016_9954_MOESM1_ESM.pdf (379 kb)
ESM 1 Analytical and bioanalytical chemistry (PDF 378 KB)


  1. 1.
    Wagner M, Tonoli D, Varesio E, Hopfgartner G. The use of mass spectrometry to analyze dried blood spots. Mass Spectrom Rev. 2016;35(3):361–438. doi: 10.1002/mas.21441.CrossRefGoogle Scholar
  2. 2.
    Li W, Tse FLS. Dried blood spot sampling in combination with LC-MS/MS for quantitative analysis of small molecules. Biomed Chromatogr. 2010;24(1):49–65. doi: 10.1002/bmc.1367.CrossRefGoogle Scholar
  3. 3.
    Wilhelm AJ, den Burger JCG, Swart EL. Therapeutic drug monitoring by dried blood spot: progress to date and future directions. Clin Pharmacokinet. 2014;53(11):961–73. doi: 10.1007/s40262-014-0177-7.CrossRefGoogle Scholar
  4. 4.
    Demirev PA. Dried blood spots: analysis and applications. Anal Chem. 2013;85(2):779–89. doi: 10.1021/ac303205m.CrossRefGoogle Scholar
  5. 5.
    Spooner N. A glowing future for dried blood spot sampling. Bioanalysis. 2010;2(8):1343–4.CrossRefGoogle Scholar
  6. 6.
    Kralj E, Trontelj J, Paji T, Kristl A. Simultaneous measurement of imatinib, nilotinib and dasatinib in dried blood spot by ultra high performance liquid chromatography tandem mass spectrometry. J Chromatogr B. 2012;903:150–6. doi: 10.1016/j.jchromb.2012.07.011.CrossRefGoogle Scholar
  7. 7.
    De Kesel PM, Capiau S, Lambert WE. Current strategies for coping with hematocrit problem in dried blood spot analysis. Bioanalysis. 2014;6(14):1871–4.CrossRefGoogle Scholar
  8. 8.
    Liu J, Wang H, Manicke NE, Lin J, Cooks RG, Ouyang Z. Development, characterization, and application of paper spray ionization. Anal Chem. 2010;82(6):2463–71.CrossRefGoogle Scholar
  9. 9.
    Wang H, Liu J, Cooks RG, Ouyang Z. Paper spray for direct analysis of complex mixtures using mass spectrometry. Angew Chem Int Ed. 2010;49(5):877–80. doi: 10.1002/anie.200906314.CrossRefGoogle Scholar
  10. 10.
    Manicke NE, Yang Q, Wang H, Oradu S, Ouyang Z, Cooks RG. Assessment of paper spray ionization for quantitation of pharmaceuticals in blood spots. Int J Mass Spectrom. 2011;300(2-3):123–9. doi: 10.1016/j.ijms.2010.06.037.CrossRefGoogle Scholar
  11. 11.
    Liu J, Manicke NE, Cooks RG, Ouyang Z. Paper spray ionization for direct analysis of dried blood spots. In: Li W, Lee MS, editors. Dried blood spots: applications and techniques. Hoboken, NJ, USA: Wiley; 2014. doi: 10.1002/9781118890837.ch23.CrossRefGoogle Scholar
  12. 12.
    Ferreira CR, Yannell KE, Jarmusch AK, Pirro V, Ouyang Z, Cooks RG. Ambient ionization mass spectrometry for point-of-care diagnostics and other clinical measurements. Clin Chem. 2015;62(1):99–110. doi: 10.1373/clinchem.2014.237164.CrossRefGoogle Scholar
  13. 13.
    Manicke NE, Bills BJ, Zhang Z. Analysis of biofluids by paper spray MS: advances and challenges. Bioanalysis. 2016;8(6):589–606.CrossRefGoogle Scholar
  14. 14.
    Kondrat RW, McClusky GA, Cooks RG. Multiple reaction monitoring in mass spectrometry/mass spectrometry for direct analysis of complex mixtures. Anal Chem. 1978;50(14):2017–21.CrossRefGoogle Scholar
  15. 15.
    Roskar R, Trdan T (2012) Analytical Methods for Quantification of Drug Metabolites in Biological Samples. InTech. doi: 10.5772/51676
  16. 16.
    Manicke NE, Belford M (2015) Separation of Opiate Isomers Using Electrospray Ionization and Paper Spray Coupled to High-Field Asymmetric Waveform Ion Mobility Spectrometry. J Am Soc Mass Spectrom. doi: 10.1007/s13361-015-1096-z
  17. 17.
    Sukumar H, Stone JA, Nishiyama T, Yuan C, Eiceman GA. Paper spray ionization with ion mobility spectrometry at ambient pressure. Int J Ion Mobil Spectrom. 2011;14(2-3):51–9. doi: 10.1007/s12127-011-0069-6.CrossRefGoogle Scholar
  18. 18.
    Manicke NE, Abu-Rabie P, Spooner N, Ouyang Z, Cooks RG. Quantitative analysis of therapeutic drugs in dried blood spot samples by paper spray mass spectrometry: an avenue to therapeutic drug monitoring. J Am Soc Mass Spectrom. 2011;22(9):1501–7. doi: 10.1007/s13361-011-0177-x.CrossRefGoogle Scholar
  19. 19.
    Espy RD, Manicke NE, Ouyang Z, Cooks RG. Rapid analysis of whole blood by paper spray mass spectrometry for point-of-care therapeutic drug monitoring. Analyst. 2012;137(10):2344. doi: 10.1039/c2an35082c.CrossRefGoogle Scholar
  20. 20.
    Su Y, Wang H, Liu J, Wei P, Cooks RG, Ouyang Z. Quantitative paper spray mass spectrometry analysis of drugs of abuse. Analyst. 2013;138(16):4443. doi: 10.1039/c3an00934c.CrossRefGoogle Scholar
  21. 21.
    Espy RD, Teunissen SF, Manicke NE, Ren Y, Ouyang Z, van Asten A, et al. Paper spray and extraction spray mass spectrometry for the direct and simultaneous quantification of eight drugs of abuse in whole blood. Anal Chem. 2014;86(15):7712–8. doi: 10.1021/ac5016408.CrossRefGoogle Scholar
  22. 22.
    Takyi-Williams J, Dong X, Gong H, Wang Y, Jian W, Liu C-F, et al. Application of paper spray–MS in PK studies using sunitinib and benzethonium as model compounds. Bioanalysis. 2015;7(4):413–23. doi: 10.4155/bio.14.288.CrossRefGoogle Scholar
  23. 23.
    Shi R-Z, El Gierari ETM, Manicke NE, Faix JD. Rapid measurement of tacrolimus in whole blood by paper spray-tandem mass spectrometry (PS-MS/MS). Clin Chim Acta. 2015;441:99–104. doi: 10.1016/j.cca.2014.12.022.CrossRefGoogle Scholar
  24. 24.
    Cortes JE, Egorin MJ, Guilhot F, Molimard M, Mahon FX. Pharmacokinetic/pharmacodynamic correlation and blood-level testing in imatinib therapy for chronic myeloid leukemia. Leukemia. 2009;23(9):1537–44. doi: 10.1038/leu.2009.88.CrossRefGoogle Scholar
  25. 25.
    Gschwind HP. Metabolism and disposition of imatinib mesylate in healthy volunteers. Drug Metab Dispos. 2005;33(10):1503–12. doi: 10.1124/dmd.105.004283.CrossRefGoogle Scholar
  26. 26.
    Abu-Rabie P, Denniff P, Spooner N, Chowdhry BZ, Pullen FS. Investigation of different approaches to incorporating internal standard in DBS quantitative bioanalytical workflows and their effect on nullifying hematocrit-based assay bias. Anal Chem. 2015;87(9):4996–5003. doi: 10.1021/acs.analchem.5b00908.CrossRefGoogle Scholar
  27. 27.
    Cheng-Huang Lin W-CL, Chen H-K, Kuo T-Y. Paper spray-MS for bioanalysis. Bioanalysis. 2014;6(2):1–10.Google Scholar
  28. 28.
    Kim J-H, Woenker T, Adamec J, Regnier FE. Simple, miniaturized blood plasma extraction method. Anal Chem. 2013;85(23):11501–8. doi: 10.1021/ac402735y.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Karen E. Yannell
    • 1
  • Kristina R. Kesely
    • 1
  • Huynh Dinh Chien
    • 2
  • Candice B. Kissinger
    • 1
  • R. Graham Cooks
    • 1
  1. 1.Department of ChemistryPurdue UniversityWest LafayetteUSA
  2. 2.Huế University of Medicine and PharmacyHuếVietnam

Personalised recommendations