Skip to main content

Advertisement

SpringerLink
Log in

Direct analysis of dried blood spots coupled with mass spectrometry: concepts and biomedical applications

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Because of the emergence of dried blood spots (DBS) as an attractive alternative to conventional venous plasma sampling in many pharmaceutical companies and clinical laboratories, different analytical approaches have been developed to enable automated handling of DBS samples without any pretreatment. Associated with selective and sensitive MS–MS detection, these procedures give good results in the rapid identification and quantification of drugs (generally less than 3 min total run time), which is desirable because of the high throughput requirements of analytical laboratories. The objective of this review is to describe the analytical concepts of current direct DBS techniques and to present their advantages and disadvantages, with particular focus on automation capacity and commercial availability. Finally, an overview of the different biomedical applications in which these concepts could be of major interest will be presented.

Direct analysis of dried blood spots

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. McDade TW, Williams S, Snodgrass JJ (2007) What a drop can do: dried blood spots as a minimally invasive method for integrating biomarkers into population-based research. Demography 44:899–925

    Article  Google Scholar 

  2. Mei JV, Alexander JR, Adam BW, Hannon WH (2001) Use of filter paper for the collection and analysis of human whole blood specimens. J Nutr 131:1631S–1636S

    CAS  Google Scholar 

  3. Lilian RR, Bhowan K, Sherman GG (2010) Early diagnosis of human immunodeficiency virus-1 infection in infants with the NucliSens EasyQ assay on dried blood spots. J Clin Virol 48:40–43

    Article  CAS  Google Scholar 

  4. Leichtle AB, Ceglarek U, Witzigmann H, Gäbel G, Thiery J, Fiedler GM (2010) Potential of dried blood self-sampling for cyclosporine C2 monitoring in transplant outpatients. J Transplant 2010:201918

    Google Scholar 

  5. Edelbroek PM, van der Heijden J, Stlok LML (2009) Dried blood spot methods in therapeutic drug monitoring: methods, assays, and pitfalls. Ther Drug Monit 31:327–336

    Article  Google Scholar 

  6. Cheung CY, van der Heijden J, Hoogtanders K, Christiaans M, Liu YL, Chan YH, Choi KS, van de Plas A, Shek CC, Chau KF, Li CS, van Hooff J, Stolk L (2008) Dried blood spot measurement: application in tacrolimus monitoring using limited sampling strategy and abbreviated AUC estimation. Transpl Int 21:140–145

    CAS  Google Scholar 

  7. Déglon J, Lauer E, Thomas A, Mangin P, Staub C (2010) Use of the dried blood spot sampling process coupled with fast gas chromatography and negative-ion chemical ionization tandem mass spectrometry: application to fluoxetine, norfluoxetine, reboxetine, and paroxetine analysis. Anal Bioanal Chem 396:2523–2532

    Article  Google Scholar 

  8. Bowen CL, Hemberger MD, Kehler JR, Evans CA (2010) Utility of dried blood spot sampling and storage for increased stability of photosensitive compounds. Bioanalysis 2:1823–1828

    Article  CAS  Google Scholar 

  9. van der Heijden J, de Beer Y, Hoogtanders K, Christiaans M, de Jong GJ, Neef C, Stolk L (2009) Therapeutic drug monitoring of everolimus using the dried blood spot method in combination with liquid chromatography–mass spectrometry. J Pharm Biomed Anal 50:664–670

    Article  Google Scholar 

  10. Guidelines for the shipment of dried blood spot specimens (1995) Center for Diseases Control and Prevention, Atlanta, GA.

  11. Parker SP, Cubitt WD (1999) The use of the dried blood spot sample in epidemiological studies. J Clin Pathol 55:633–639

    Article  Google Scholar 

  12. Patel P, Mulla H, Tanna S, Pandya H (2010) Facilitating pharmacokinetic studies in children: a new use of dried blood spots. Arch Dis Child 95:484–487

    Article  Google Scholar 

  13. Suyagh MF, Iheagwaram G, Kole PL, Millership J, Collier P, Halliday H, McElnay JC (2010) Development and validation of a dried blood spot-HPLC assay for the determination of metronidazole in neonatal whole blood samples. Anal Bioanal Chem 397:687–693

    Article  CAS  Google Scholar 

  14. Boy RG, Henseler J, Mattern R, Skopp G (2008) Determination of morphine and 6-acetylmorphine in blood with use of dried blood spots. Ther Drug Monit 30:733–739

    Article  Google Scholar 

  15. Thomas A, Déglon J, Steimer T, Mangin P, Daali Y, Staub C (2010) 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. J Sep Sci 33:873–879

    Article  CAS  Google Scholar 

  16. Beaudette P, Bateman KP (2004) Discovery stage pharmacokinetics using dried blood spots. J Chromatogr B 809:153–158

    Article  CAS  Google Scholar 

  17. Damen CWN, Rosing H, Schellens JHM, Beijnen JH (2009) Application of dried blood spots combined with high-performance liquid chromatography coupled with electrospray ionisation tandem mass spectrometry for simultaneous quantification of vincristine and actinomycin-D. Anal Bioanal Chem 394:1171–1182

    Article  CAS  Google Scholar 

  18. van Amsterdam P, Waldrop C (2010) The application of dried blood spot sampling in global clinical trials. Bioanalysis 2:1783–1786

    Article  Google Scholar 

  19. Li W, Tse FLS (2010) Dried blood spot sampling in combination with LC–MS–MS for quantitative analysis of small molecules. Biomed Chromatogr 24:49–65

    Article  Google Scholar 

  20. Keevil BG (2011) The analysis of dried blood spot samples using liquid chromatography tandem mass spectrometry. J Clin Biochem 44:110–118

    Article  CAS  Google Scholar 

  21. Guthrie R, Suzi A (1963) A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics 32:338–343

    CAS  Google Scholar 

  22. Tran TN, de Vries PJ, Hoang LP, Phan GT, Le HQ, Tran BQ, Vo CM, Nguyen NV, Kager PA, Nagelkerke N, Groen J (2006) Enzyme-linked immunoassay for dengue virus IgM and IgG antibodies in serum and filter paper blood. Biomed Central Infect Dis 6:13–20

    Google Scholar 

  23. Hofmana L, Foleya TP, Henrya JJ, Naylora EW (2004) The use of filter paper-dried blood spots for thyroid-antibody screening in adults. J Lab Clin Med 144:307–312

    Article  Google Scholar 

  24. Lewensohn-Fuchs I, Osterwall P, Forsgren M, Malm G (2003) Detection of herpes simplex virus DNA in dried blood spots making a retrospective diagnosis possible. J Clin Virol 26:39–48

    Article  Google Scholar 

  25. Stevens W, Erasmus L, Moloi M, Taleng T, Sarang S (2008) Performance of a novel human immunodeficiency virus (HIV) type 1 total nucleic acid-based real-time PCR Assay using whole blood and dried blood spots for diagnosis of HIV in infants. J Clin Micr 46:3941–3945

    Article  CAS  Google Scholar 

  26. Langkamp M, Weber K, Ranke MB (2008) Human growth hormone measurement by means of a sensitive ELISA of whole blood spots on filter paper. Growth Horm IGF Res 18:526–532

    Article  CAS  Google Scholar 

  27. McDade TW, Burhop J, Dohnal J (2004) High-sensitivity enzyme immunoassay for C-reactive protein in dried blood spots. Clin Chem 50:652–654

    Article  CAS  Google Scholar 

  28. Mwaba P, Cassol S, Pilon R, Chintu C, Janes M, Nunn A, Zumla (2003) A Use of dried whole blood spots to measure CD4+ lymphocyte counts in HIV-1-infected patients. Lancet 362:1459–1460

    Article  CAS  Google Scholar 

  29. Oliveira EJ, Watson DG, Morton NS (2002) A simple microanalytical technique for the determination of paracetamol and its main metabolites in blood spots. J Pharm Biomed Anal 29:803–809

    Article  CAS  Google Scholar 

  30. Al A, Cotton MM, Tettey JNA, Boyter AC (2007) Determination of rifampicin in human plasma and blood spots by high performance liquid chromatography with UV detection: a potential method for therapeutic drug monitoring. J Pharm Biomed Anal 44:963–969

    Article  Google Scholar 

  31. Ntale M, Mahindi M, Ogwal-Okeng JW, Gustafsson LL, Beck O (2007) A field-adapted HPLC method for determination of amodiaquine and its metabolite in whole blood dried on filter paper. J Chromatogr B 859:137–140

    Article  CAS  Google Scholar 

  32. Thomas A, Lenglet S, Chaurand P. Déglon J, Mangin P, Mach F, Steffens S, Wolfender J-L, Staub C (2011) Thromb Haemost (in press).

  33. Koal T, Burhenne H, Römling R, Svoboda M, Resch K, Kaever V (2005) Quantification of antiretroviral drugs in dried blood spot samples by means of liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 19:2995–3001

    Article  CAS  Google Scholar 

  34. Zytkovicz TH, Fitzgerlad EF, Marsden D, Larson CA, Shih VE, Johnson DM, Strauss AW, Comeau AM, Eaton RB, Grady GF (2001) Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England Newborn Screening Program. Clin Chem 47:1945–1955

    CAS  Google Scholar 

  35. la Marca G, Malvagia S, Filippi L, Fiorini P, Innocenti M, Luceri F, Pieraccini G, Moneti G, Francese S, Dani FR, Guerrini R (2008) Rapid assay of topiramate in dried blood spots by a new liquid chromatography–tandem mass spectrometric method. J Pharm Biomed Anal 48:1392–1396

    Article  Google Scholar 

  36. Barfield M, Spooner N, Lad R, Parry S, Fowles S (2008) Application of dried blood spots combined with HPLC–MS–MS for the quantification of acetaminophen in toxicokinetic studies. J Chromatogr B 870:32–37

    Article  CAS  Google Scholar 

  37. Kato K, Wanigatunga AA, Needham LL, Calafat AM (2009) Analysis of blood spots for polyfluoroalkyl chemicals. Anal Chim Acta 656:51–55

    Article  CAS  Google Scholar 

  38. Déglon J, Thomas A, Cataldo A, Mangin P, Staub C (2009) On-line desorption of dried blood spot: a novel approach for the direct LC–MS analysis of micro-whole blood samples. J Pharm Biomed Anal 49:1034–1039

    Article  Google Scholar 

  39. Déglon J, Thomas A, Daali Y, Lauer E, Samer C, Desmeules J, Dayer P, Mangin P, Staub C (2011) Automated system for on-line desorption of dried blood spots applied to LC/MS–MS pharmacokinetic study of flurbiprofen and its metabolite. J Pharm Biomed Anal 54:359–367

    Article  Google Scholar 

  40. Thomas A, Déglon J, Lenglet S, Mach F, Mangin P, Wolfender J-L, Steffens S, Staub C (2010) High-throughput phospholipidic fingerprinting by online desorption of dried spots and quadrupole–linear ion trap mass spectrometry: evaluation of atherosclerosis biomarkers in mouse plasma. Anal Chem 82:6687–6694

    Article  CAS  Google Scholar 

  41. Ooms B (2010) On-line DBS–SPE–MS–MS: Feasibility of a concept for rapid DBS analysis without punching. Oral presentation. Presented at EBF workshop connecting strategies on Dried Blood Spots, Brussels, Belgium.

  42. Miller JH IV, Poston PA, Karnes HT (2011) Direct analysis of dried blood spots by in-line desorption combined with high-resolution chromatography and mass spectrometry for quantification of maple syrup urine disease biomarkers leucine and isoleucine. Anal Bioanal Chem 400:237–244

    Article  CAS  Google Scholar 

  43. Heinig K, Wirz T, Bucheli F, Gajate-Perez A (2011) Determination of oseltamivir (Tamiflu®) and oseltamivir carboxylate in dried blood spots using offline or online extraction. Bioanalysis 3:421–437

    Article  CAS  Google Scholar 

  44. Heinig K, Wirz T, Gajate-Perez A (2010) Sensitive determination of a drug candidate in dried blood spots using a TLC–MS interface integrated into column-switching LC–MS–MS system. Bioanalysis 2:1873–1882

    Article  CAS  Google Scholar 

  45. Van Berkel GJ, Kertesz V (2009) Application of a liquid extraction based sealing surface sampling probe for mass spectrometric analysis of dried blood spots and mouse whole-body thin tissue sections. Anal Chem 21:9146–9152

    Article  Google Scholar 

  46. Luftmann H (2004) A simple device for the extraction of TLC spots: direct coupling with an electrospray mass spectrometer. Anal Bioanal Chem 378:964–968

    Article  CAS  Google Scholar 

  47. Morlock G, Schwack W (2010) Coupling of planar chromatography to mass spectrometry. Trends Anal Chem 29:1157–1171

    Article  CAS  Google Scholar 

  48. Luftmann H, Aranda M, Morlock GE (2007) Automated interface for hyphenation of planar chromatography with mass spectrometry. Rapid Commun Mass Spectrom 21:3772–3776

    Article  CAS  Google Scholar 

  49. Abu-Rabie P, Spooner N (2009) Direct quantitative bioanalysis of drugs in dried blood spot samples using thin-layer chromatography mass spectrometer interface. Anal Chem 24:10275–10284

    Article  Google Scholar 

  50. Zimmer D, Sack S, Betschart B, Fankhauser C, Loppacher M (2011) 59th ASMS conference on mass spectrometry and allied topics. J Am Soc Mass Spectrom 22(S1):162

    Google Scholar 

  51. Van Berkel GJ, Kertesz V, King RC (2009) High-throughput mode liquid microjunction surface sampling probe. Anal Chem 81:7096–7101

    Article  Google Scholar 

  52. Kertesz V, Van Berkel GJ (2010) Fully automated liquid extraction-based surface sampling and ionization using a chip-based robotic nanoelectrospray platform. J Mass Spectrom 45:252–260

    Article  CAS  Google Scholar 

  53. Harris GA, Nyadong L, Fernandez FM (2008) Recent developments in ambient ionization techniques for analytical mass spectrometry. Analyst 133:1297–1301

    Article  CAS  Google Scholar 

  54. Ifa DR, Wu C, Ouyang Z, Cooks RG (2010) Desorption electrospray ionization and other ambient ionization methods: current progress and preview. Analyst 135:669–681

    Article  CAS  Google Scholar 

  55. Cooks RG, Ouyang Z, Takats Z, Wiseman JM (2006) Detection technologies. Ambient mass spectrometry. Science 311:1566–1570

    Article  CAS  Google Scholar 

  56. Costa AB, Cooks RG (2007) Simulation of atmospheric transport and droplet–thin film collisions in desorption electrospray ionization. Chem Commun 14:3915–3917

    Article  Google Scholar 

  57. Wiseman JM, Evans CA, Bowen CL, Kennedy JH (2010) Direct analysis of dried blood spots utilizing desorption electrospray ionization (DESI) mass spectrometry. Analyst 135:720–725

    Article  CAS  Google Scholar 

  58. Liu J, Wang H, Manicke NE, Lin J-M, Cooks RG, Ouyang Z (2010) Development, characterization, and application of paper spray ionization. Anal Chem 82:2463–2471

    Article  CAS  Google Scholar 

  59. Wang H, Liu J, Cooks RG, Ouyang Z (2010) Paper spray for direct analysis of complex mixtures using mass spectrometry. Angew Chem 49:877–880

    CAS  Google Scholar 

  60. Chace DH, Kalas TA, Naylor EW (2002) The application of tandem mass spectrometry to neonatal screening for inherited disorders of intermediary metabolism. Annu Rev Genomics Hum Genet 3:17–45

    Article  CAS  Google Scholar 

  61. Wilcken B, Wiley V (2008) Newborn screening. Pathology 40:104–105

    Article  Google Scholar 

  62. Corso G, D’Apolito O, Gelzo M, Paglia G, Dello Russo A (2010) A powerful couple in the future of clinical biochemistry: in situ analysis of dried blood spots by ambient mass spectrometry. Bioanalysis 2:1883–1891

    Article  CAS  Google Scholar 

  63. Sturm S, Hammann F, Drewe J, Maurer HH, Scholer A (2010) An automated screening method for drugs and toxic compounds in human serum and urine using liquid chromatography–tandem mass spectrometry. J Chromatogr B 878:2726–2732

    Article  CAS  Google Scholar 

  64. Decaestecker TN, Vande Casteele SR, Wallemacq PE, Van Peteghem CH, Defore DL, Van Bocxlaer JF (2004) Information-dependent acquisition-mediated LC–MS–MS screening procedure with semiquantitative potential. Anal Chem 76:6365–6373

    Article  CAS  Google Scholar 

  65. Mylonas R, Mauron Y, Masselot A, Binz P-A, Budin N, Fathi M, Viette V, Hochstrasser DF, Lisacek F (2009) X-rank: a robust algorithm for small molecule identification using tandem mass spectrometry. Anal Chem 81:7604–7610

    Article  CAS  Google Scholar 

  66. Wong P, Pham R, Bruenner BA, James CA (2010) Increasing efficiency for dried blood spot analysis: prospects for automation and simplified sample analysis. Bioanalysis 2:1787–1789

    Article  CAS  Google Scholar 

  67. Spooner N, Lad R, Barfield M (2009) Dried blood spots as a sample collection technique for the determination of pharmacokinetics in clinical studies: considerations for the validation of a quantitative bioanalytical method. Anal Chem 81:1557–1563

    Article  CAS  Google Scholar 

  68. Mauriala T, Chauret N, Oballa R, Nicoll-Griffith DA, Bateman KP (2005) A strategy for identification of drug metabolites from dried blood spots using triple-quadrupole/linear ion trap hybrid mass spectrometry. Rapid Commun Mass Spectrom 19:1984–1992

    Article  CAS  Google Scholar 

  69. Hill H (2009) Developing trends in bioanalysis. Bioanalysis 1:1359–1364

    Article  CAS  Google Scholar 

  70. Anderson NL, Anderson NG (2002) The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 1:845–867

    Article  CAS  Google Scholar 

  71. Anderson L (2005) Candidate-based proteomics in the search for biomarkers of cardiovascular disease. J Physiol 563:23–60

    Article  CAS  Google Scholar 

  72. Surinova S, Schiess R, Hüttenhain R, Cerciello F, Wollscheid B, Aebersold R (2011) On the development of plasma protein biomarkers. J Proteom Res 10:5–16

    Article  CAS  Google Scholar 

Download references

Conflict of interest/disclosure

The authors declare no conflicts of interest regarding this manuscript.

Author information

Authors and Affiliations

  1. Unit of Toxicology, CURML, 1 rue Michel-Servet, 1211, Geneva 4, Switzerland

    Julien Déglon, Aurélien Thomas, Patrice Mangin & Christian Staub

  2. Swiss Centre for Applied Human Toxicology, University of Geneva, 1211, Geneva, Switzerland

    Julien Déglon, Aurélien Thomas & Christian Staub

Authors
  1. Julien Déglon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aurélien Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrice Mangin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christian Staub
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christian Staub.

Additional information

Published in the special issue Analytical Sciences in Switzerland with guest editors P. Dittrich, D. Günther, G. Hopfgartner, and R. Zenobi.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary Material

(PDF 95 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Déglon, J., Thomas, A., Mangin, P. et al. Direct analysis of dried blood spots coupled with mass spectrometry: concepts and biomedical applications. Anal Bioanal Chem 402, 2485–2498 (2012). https://doi.org/10.1007/s00216-011-5161-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-011-5161-6

Keywords

Search

Navigation