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Dried matrix spots: an evolving trend in the toxicological field

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Abstract

Dried matrix spot (DMS) is a sampling technique, primarily used to analyze blood to diagnose metabolic diseases in newborns. As this technique has several advantages, DMS has started to be employed for other purposes using other biological matrices and increasingly in toxicology over the last decade. The aim of this work was to review the analytical methods using DMS which can be applied to drugs of abuse and which have been published since 2010. Three different databases were searched, using dried, spots, and drugs of abuse as the descriptors and using a snowball search. After applying the exclusion criteria, 39 papers remained. The most common publications were related to the use of blood, which corresponded to 77% of the papers, followed by urine and oral fluid, which corresponded to 13 and 10% of the papers, respectively. The selected studies covered different illicit drugs, sample sizes of 5 to 250 µL and spot sizes ranging from 3 to 18 mm in diameter. This review also examined the extraction techniques and the methods employed to analyze various biological matrices and drugs of abuse, mostly by liquid-extraction and liquid chromatography-tandem mass spectrometry. The benefits of DMS include: a simple sample pretreatment, better stability than liquid matrices, a simple extraction procedure, lower costs, and environmental benefits. DMS appears to be a promising technique in the field of toxicology and provides new perspectives for use in forensic laboratories.

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References

  1. Déglon J, Thomas A, Cataldo A, Mangin P, Staub C. On-line desorption of dried blood spot: a novel approach for the direct LC/MS analysis of μ-whole blood samples. J Pharm Biomed Anal. 2009;49:1034–9.

    Article  PubMed  Google Scholar 

  2. Déglon J, Thomas A, Mangin P, Staub C. Direct analysis of dried blood spots coupled with mass spectrometry: concepts and biomedical applications. Anal Bioanal Chem. 2012;402:2485–98.

    Article  PubMed  Google Scholar 

  3. Liu J, Manicke NE, Graham Cooks R, Ouyang Z. Paper spray ionization for direct analysis of dried blood spots. In: Li W, Lee MS, editors. Dried blood spots Appl Tech. 1st ed. Hoboken, New Jersey, USA: John Wiley & Sons, Inc.; 2014. p. 298–313.

    Google Scholar 

  4. Millington DS, Sista R, Bali D, Eckhardt AE, Pamula V. Development of biomarker assays for clinical diagnostics using a digital microfluidics platform. In: Li W, Lee MS, editors. Dried blood spots Appl Tech. 1st ed. Hoboken, New Jersey, USA: John Wiley & Sons, Inc.; 2014. p. 325–31.

    Google Scholar 

  5. Abu-rabie P. Direct analysis of dried blood spot samples. In: Li W, Lee MS, editors. Dried blood spots Appl Tech. 1st ed. Hoboken, New Jersey, USA: John Wiley & Sons, Inc.; 2014. p. 245–97.

    Google Scholar 

  6. Guthrie R. Blood screening for phenylketonuria Jama. 1961;178:863–863.

    Google Scholar 

  7. Guthrie R, Susi A. A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics. 1963;32:338–43.

    Article  CAS  PubMed  Google Scholar 

  8. Martial LC, Aarnoutse RE, Mulder M, Schellekens A, Brüggemann RJM, Burger DM, et al. Dried blood spot sampling in psychiatry: perspectives for improving therapeutic drug monitoring. Eur Neuropsychopharmacol. 2017;27:205–16.

    Article  CAS  PubMed  Google Scholar 

  9. Edelbroek PM, Heijden JVD, Stolk LML. Dried blood spot methods in therapeutic drug monitoring: methods, assays, and pitfalls. Ther Drug Monit. 2009;31:327–36.

    Article  PubMed  Google Scholar 

  10. Wickremsinhe ER, Perkins EJ. Using dried blood spot sampling to improve data quality and reduce animal use in mouse pharmacokinetic studies. J Am Assoc Lab Anim Sci. 2015;54:139–44.

    PubMed  PubMed Central  Google Scholar 

  11. Turpin PE, Burnett JEC, Goodwin L, Foster A, Barfield M. Application of the DBS methodology to a toxicokinetic study in rats and transferability of analysis between bioanalytical laboratories. Bioanalysis. 2010;2:1489–99.

    Article  CAS  PubMed  Google Scholar 

  12. Mercolini L, Mandrioli R, Gerra G, Raggi MA. Analysis of cocaine and two metabolites in dried blood spots by liquid chromatography with fluorescence detection: a novel test for cocaine and alcohol intake. J Chromatogr A. 2010;1217:7242–8.

    Article  CAS  PubMed  Google Scholar 

  13. Zheng N, Zeng J, Ji QC, Angeles A, Aubry AF, Basdeo S, et al. Bioanalysis of dried saliva spot (DSS) samples using detergent-assisted sample extraction with UHPLC-MS/MS detection. Anal Chim Acta. 2016;934:170–9.

    Article  CAS  PubMed  Google Scholar 

  14. Otero-Fernández M, Cocho JÁ, Tabernero MJ, Bermejo AM, Bermejo-Barrera P, Moreda-Piñeiro A. Direct tandem mass spectrometry for the simultaneous assay of opioids, cocaine and metabolites in dried urine spots. Anal Chim Acta. 2013;784:25–32.

    Article  PubMed  Google Scholar 

  15. Lee Y, Lai KKY, Sadrzadeh SMH. Simultaneous detection of 19 drugs of abuse on dried urine spot by liquid chromatography-tandem mass spectrometry. Clin Biochem. The Canadian Society of Clinical Chemists. 2013;46:1118–24. https://doi.org/10.1016/j.clinbiochem.2013.03.027

  16. Chace DH, Lappas NT. The use of dried blood spots and stains in forensic science. In: Li W, Lee MS, editors. Dried blood spots Appl Tech. 1st ed. Hoboken, New Jersey, USA: John Wiley & Sons, Inc.; 2014. p. 140–50.

    Google Scholar 

  17. Henderson LO, Powell MK, Hannon WH, Bernert JT, Pass KA, Fernhoff P, et al. An evaluation of the use of dried blood spots from newborn screening for monitoring the prevalence of cocaine use among childbearing women. Biochem Mol Med. 1997;61:143–51.

    Article  CAS  PubMed  Google Scholar 

  18. Antunes MV, Niederauer CG, Linden R. Development, validation and clinical evaluation of a dried urine spot method for determination of hippuric acid and creatinine. Clin Biochem. 2013;46:1276–80.

    Article  CAS  PubMed  Google Scholar 

  19. Wilcox RL, Nelson CC, Stenzel P, Steiner RD. Postmortem screening for fatty acid oxidation disorders by analysis of Guthrie cards with tandem mass spectrometry in sudden unexpected death in infancy. J Pediatr. 2002;141:833–6.

    Article  CAS  PubMed  Google Scholar 

  20. Jantos R. Comparison of the determination of drugs with influence on driving performance in serum, whole blood and dried blood spots. Toxichem Krimtech. 2013;80:49–59.

    Google Scholar 

  21. Schütz H, Gotta JC, Erdmann F, Riße M, Weiler G. Simultaneous screening and detection of drugs in small blood samples and bloodstains. Forensic Sci Int. 2002;126:191–6.

    Article  PubMed  Google Scholar 

  22. Mueller F, Losacco GL, Nicoli R, Guillarme D, Thomas A, Grata E. Enantiomeric methadone quantitation on real post-mortem dried matrix spots samples: comparison of liquid chromatography and supercritical fluid chromatography coupled to mass spectrometry. J Chromatogr B. 2021;1177:122755.

  23. Kacargil CU, Daglioglu N, Goren IE. Determination of illicit drugs in dried blood spots by LC–MS/MS method: validation and application to real samples. Chromatographia . Springer Berlin Heidelberg. 2020;83:885–92.

  24. Gorziza R, Cox J, Pereira Limberger R, Arroyo-Mora LE. Extraction of dried oral fluid spots (DOFS) for the identification of drugs of abuse using liquid chromatography tandem mass spectrometry (LC-MS/MS). Forensic Chem. Elsevier. 2020;19:100254.

  25. Yan X, Yuan S, Yu Z, Zhao Y, Zhang S, Wu H, et al. Development of an LC-MS/MS method for determining 5-MeO-DIPT in dried urine spots and application to forensic cases. J Forensic Leg Med. 2020;72:101963.

  26. Pablo A, Breaud AR, Clarke W. Automated analysis of dried urine spot (DUS) samples for toxicology screening. Clin Biochem. 2020;75:70–7.

    Article  PubMed  Google Scholar 

  27. Jacques ALB, dos Santos MK, Limberger RP. Development and validation of a method using dried oral fluid spot to determine drugs of abuse. J Forensic Sci. 2019;64:1906–12.

    Article  CAS  PubMed  Google Scholar 

  28. Joye T, Sidibé J, Déglon J, Karmime A, Sporkert F, Widmer C, et al. Liquid chromatography-high resolution mass spectrometry for broad-spectrum drug screening of dried blood spot as microsampling procedure. Anal Chim Acta. 2019;1063:110–6.

    Article  CAS  PubMed  Google Scholar 

  29. Seymour C, Shaner RL, Feyereisen MC, Wharton RE, Kaplan P, Hamelin EI, et al. Determination of fentanyl analog exposure using dried blood spots with LC-MS-MS. J Anal Toxicol. 2019;43:266–76.

    Article  CAS  PubMed  Google Scholar 

  30. Lizot LDLF, da Silva AC, Bastiani MF, Hahn RZ, Bulcão R, Perassolo MS, et al. Simultaneous determination of cocaine, ecgonine methyl ester, benzoylecgonine, cocaethylene and norcocaine in dried blood spots by ultra-performance liquid chromatography coupled to tandem mass spectrometry. Forensic Sci Int. 2019;298:408–16.

  31. Ambach L, Stove C. Determination of cocaine and metabolites in dried blood spots by LC-MS/MS. In: Langman L, Snozek C, editors. LC-MS drug anal methods Mol Biol. New York, NY: Humana Press; 2019. p. 261–72.

    Google Scholar 

  32. Ribeiro A, Prata M, Vaz C, Rosado T, Restolho J, Barroso M, et al. Determination of methadone and EDDP in oral fluid using the dried saliva spots sampling approach and gas chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2019;411:2177–87.

    Article  CAS  PubMed  Google Scholar 

  33. Moretti M, Visonà SD, Freni F, Tomaciello I, Vignali C, Groppi A, et al. A liquid chromatography–tandem mass spectrometry method for the determination of cocaine and metabolites in blood and in dried blood spots collected from postmortem samples and evaluation of the stability over a 3-month period. Drug Test Anal. 2018;10:1430–7.

    Article  CAS  PubMed  Google Scholar 

  34. Simões SS, Ajenjo AC, Dias MJ. Dried blood spots combined to an UPLC–MS/MS method for the simultaneous determination of drugs of abuse in forensic toxicology. J Pharm Biomed Anal . 2018;147:634–44. https://linkinghub.elsevier.com/retrieve/pii/S0731708516306100.

  35. Protti M, Rudge J, Sberna AE, Gerra G, Mercolini L. Dried haematic microsamples and LC–MS/MS for the analysis of natural and synthetic cannabinoids. J Chromatogr B Anal Technol Biomed Life Sci. Elsevier B.V. 2017;1044–1045:77–86.https://doi.org/10.1016/j.jchromb.2016.12.038.

  36. Chepyala D, Tsai IL, Liao HW, Chen GY, Chao HC, Kuo CH. Sensitive screening of abused drugs in dried blood samples using ultra-high-performance liquid chromatography-ion booster-quadrupole time-of-flight mass spectrometry. J Chromatogr A. 2017;1491:57–66.

    Article  CAS  PubMed  Google Scholar 

  37. Shaner RL, Schulze ND, Seymour C, Hamelin EI, Thomas JD, Johnson RC. Quantitation of fentanyl analogs in dried blood spots by flow-through desorption coupled to online solid phase extraction tandem mass spectrometry. Anal Methods Royal Society of Chemistry. 2017;9:3876–83.

    CAS  Google Scholar 

  38. Michely JA, Meyer MR, Maurer HH. Dried urine spots - a novel sampling technique for comprehensive LC-MSn drug screening. Anal Chim Acta. 2017;982:112–21.

    Article  CAS  PubMed  Google Scholar 

  39. Kyriakou C, Marchei E, Scaravelli G, García-Algar O, Supervía A, Graziano S. Identification and quantification of psychoactive drugs in whole blood using dried blood spot (DBS) by ultra-performance liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal. 2016;128:53–60.

    Article  CAS  PubMed  Google Scholar 

  40. Sadones N, Van Bever E, Archer JRH, Wood DM, Dargan PI, Van Bortel L, et al. Microwave-assisted on-spot derivatization for gas chromatography–mass spectrometry based determination of polar low molecular weight compounds in dried blood spots. J Chromatogr A. 2016;1465:175–83.

    Article  CAS  PubMed  Google Scholar 

  41. Verplaetse R, Henion J. Quantitative determination of opioids in whole blood using fully automated dried blood spot desorption coupled to on-line SPE-LC-MS/MS. Drug Test Anal. 2016;8:30–8.

    Article  CAS  PubMed  Google Scholar 

  42. Stoykova S, Kanev K, Pantcheva I, Atanasov V. Isolation and characterization of drugs of abuse in oral fluid by a novel preconcentration protocol. Anal Lett. 2016;49:2822–32.

    Article  CAS  Google Scholar 

  43. Ellefsen KN, da Costa JL, Concheiro M, Anizan S, Barnes AJ, Pirard S, et al. Cocaine and metabolite concentrations in DBS and venous blood after controlled intravenous cocaine administration. Bioanalysis. 2015;7:2041–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Odoardi S, Anzillotti L, Strano-Rossi S. Simplifying sample pretreatment: application of dried blood spot (DBS) method to blood samples, including postmortem, for UHPLC-MS/MS analysis of drugs of abuse. Forensic Sci Int. 2014;243:61–7.

    Article  CAS  PubMed  Google Scholar 

  45. Versace F, Déglon J, Lauer E, Mangin P, Staub C. Automated DBS extraction prior to hilic/RP LC-MS/MS target screening of drugs. Chromatographia. 2013;76:1281–93.

    Article  CAS  Google Scholar 

  46. Ambach L, Hernández Redondo A, König S, Weinmann W. Rapid and simple LC-MS/MS screening of 64 novel psychoactive substances using dried blood spots. Drug Test Anal. 2014;6:367–75.

    Article  CAS  PubMed  Google Scholar 

  47. Mercolini L, Mandrioli R, Sorella V, Somaini L, Giocondi D, Serpelloni G, et al. Dried blood spots: liquid chromatography-mass spectrometry analysis of Δ9-tetrahydrocannabinol and its main metabolites. J Chromatogr A. 2013;1271:33–40.

    Article  CAS  PubMed  Google Scholar 

  48. Antelo-Domínguez Á, Cocho JÁ, Tabernero MJ, Bermejo AM, Bermejo-Barrera P, Moreda-Piñeiro A. Simultaneous determination of cocaine and opiates in dried blood spots by electrospray ionization tandem mass spectrometry. Talanta. 2013;117:235–41.

    Article  PubMed  Google Scholar 

  49. Thomas A, Geyer H, Schänzer W, Crone C, Kellmann M, Moehring T, et al. Sensitive determination of prohibited drugs in dried blood spots (DBS) for doping controls by means of a benchtop quadrupole/Orbitrap mass spectrometer. Anal Bioanal Chem. 2012;403:1279–89.

    Article  CAS  PubMed  Google Scholar 

  50. Saussereau E, Lacroix C, Gaulier JM, Goulle JP. On-line liquid chromatography/tandem mass spectrometry simultaneous determination of opiates, cocainics and amphetamines in dried blood spots. J Chromatogr B. 2012;885–886:1–7.

    Article  Google Scholar 

  51. Saracino MA, Marcheselli C, Somaini L, Pieri MC, Gerra G, Ferranti A, et al. A novel test using dried blood spots for the chromatographic assay of methadone. Anal Bioanal Chem. 2012;404:503–11.

    Article  CAS  PubMed  Google Scholar 

  52. Clavijo CF, Hoffman KL, Thomas JJ, Carvalho B, Chu LF, Drover DR, et al. A sensitive assay for the quantification of morphine and its active metabolites in human plasma and dried blood spots using high-performance liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2011;400:715–28.

    Article  CAS  PubMed  Google Scholar 

  53. Clavijo CF, Thomas JJ, Cromie M, Schniedewind B, Hoffman KL, Christians U, et al. A low blood volume LC-MS/MS assay for the quantification of fentanyl and its major metabolites norfentanyl and despropionyl fentanyl in children. J Sep Sci. 2011;34:3568–77.

    Article  CAS  PubMed  Google Scholar 

  54. Jantos R, Veldstra JL, Mattern R, Brookhuis KA, Skopp G. Analysis of 3,4-methylenedioxymetamphetamine: whole blood versus dried blood spots. J Anal Toxicol. 2011;35:269–73.

    Article  CAS  PubMed  Google Scholar 

  55. Ingels AS, De Paepe P, Anseeuw K, Van Sassenbroeck D, Neels H, Lambert W, et al. Dried blood spot punches for confirmation of suspected γ- hydroxybutyric acid intoxications: validation of an optimized GC-MS procedure. Bioanalysis. 2011;3:2271–81.

    Article  CAS  PubMed  Google Scholar 

  56. Thomas A, Déglon J, Steimer T, Mangin P, Daali Y, Staub C. On-line desorption of dried blood spots coupled to hydrophilic interaction/reversedphase LC/MS/MS system for the simultaneous analysis of drugs and their polar metabolites. J Sep Sci. 2010;33:873–9.

    Article  CAS  PubMed  Google Scholar 

  57. Ingels ASME, Lambert WE, Stove CP. Determination of gamma-hydroxybutyric acid in dried blood spots using a simple GC-MS method with direct “on spot” derivatization. Anal Bioanal Chem. 2010;398:2173–82.

    Article  CAS  PubMed  Google Scholar 

  58. Wong P, James CA. Punching and extraction techniques for dried blood spot sample analysis. In: Li W, Lee MS, editors. Dried blood spots Appl Tech. 1st ed. Hoboken, New Jersey, USA: John Wiley & Sons, Inc.; 2014. p. 160–7.

    Google Scholar 

  59. Schepers RJF, Oyler JM, Joseph RE, Cone EJ, Moolchan ET, Huestis MA. Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers. Clin Chem. 2003;49:121–32.

    Article  CAS  PubMed  Google Scholar 

  60. Allen KR. Screening for drugs of abuse: which matrix, oral fluid or urine? Ann Clin Biochem. 2011;48:531–41.

    Article  CAS  PubMed  Google Scholar 

  61. Jesús VR de, Chace DH. Letter to the editor: commentary on the history and quantitative nature of filter paper used in blood collection devices. Bioanalysis. 2012;4:645–7. http://www.future-science.com/doi/https://doi.org/10.4155/bio.12.34.

  62. Davin B, Hannon WH. Dried blood spot cards. In: Li W, Lee MS, editors. Dried blood spots Appl Tech. 1st ed. Hoboken, New Jersey, USA: John Wiley & Sons, Inc.; 2014. p. 16–20.

    Google Scholar 

  63. CLSI. Dried blood spot specimen collection for newborn screening. 7th ed. USA: Clinical and Laboratory Standards Institute. 2021.

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

    Article  CAS  PubMed  Google Scholar 

  65. Hannon WH, Therrell BL. Overview of the history and applications of dried blood samples. In: Li W, Lee MS, editors. Dried blood spots Appl Tech. 1st ed. Hoboken, New Jersey, USA: John Wiley & Sons, Inc.; 2014. p. 1–15.

    Google Scholar 

  66. Ambach L, Menzies E, Parkin MC, Kicman A, Archer JRH, Wood DM, et al. Quantification of cocaine and cocaine metabolites in dried blood spots from a controlled administration study using liquid chromatography–tandem mass spectrometry. Drug Test Anal. 2019;11:709–20.

    Article  CAS  PubMed  Google Scholar 

  67. Mommers J, Mengerink Y, Ritzen E, Weusten J, van der Heijden J, van der Wal S. Quantitative analysis of morphine in dried blood spots by using morphine-d3 pre-impregnated dried blood spot cards. Anal Chim Acta. Elsevier B.V. 2013;774:26–32. https://doi.org/10.1016/j.aca.2013.03.001.

  68. Enderle Y, Foerster K, Burhenne J. Clinical feasibility of dried blood spots: Analytics, validation, and applications. J Pharm Biomed Anal. 2016;130:231–43.

    Article  CAS  PubMed  Google Scholar 

  69. Alfazil AA, Anderson RA. Stability of benzodiazepines and cocaine in blood spots stored on filter paper. J Anal Toxicol. 2008;32:511–5.

    Article  CAS  PubMed  Google Scholar 

  70. Boy RG, Henseler J, Mattern R, Skopp G. Determination of morphine and 6-acetylmorphine in blood with use of dried blood spots. Ther Drug Monit. 2008;30:733–9.

    Article  Google Scholar 

  71. Chen X, Zhao H, Hatsis P, Amin J. Investigation of dried blood spot card-induced interferences in liquid chromatography/mass spectrometry. J Pharm Biomed Anal. 2012;61:30–7.

    Article  CAS  PubMed  Google Scholar 

  72. Van AP, Waldrop C. The application of dried blood spot sampling in global clinical trials. Bioanalysis. 2010;2:1783–6.

    Article  Google Scholar 

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Funding

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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  1. Faculty of Pharmacy, Federal University of Rio Grande Do Sul, Porto Alegre, Brazil

    Ana Laura Bemvenuti Jacques, Maíra Kerpel Santos, Roberta Petry Gorziza & Renata Pereira Limberger

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  1. Ana Laura Bemvenuti Jacques
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  2. Maíra Kerpel Santos
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  3. Roberta Petry Gorziza
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  4. Renata Pereira Limberger
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All the authors have made substantial contributions to the manuscript. Ana Laura B. Jacques had the idea for the article; Ana Laura B. Jacques, Maíra K. Santos, and Roberta P. Gorziza performed the literature search and data analysis, and Renata P. Limberger advised the preparation of the review.

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Correspondence to Ana Laura Bemvenuti Jacques.

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Jacques, A.L.B., Santos, M.K., Gorziza, R.P. et al. Dried matrix spots: an evolving trend in the toxicological field. Forensic Sci Med Pathol 18, 86–102 (2022). https://doi.org/10.1007/s12024-021-00434-5

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