DropWise: current role and future perspectives of dried blood spots (DBS), blood microsampling, and their analysis in sports drug testing

Abstract For decades, blood testing has been an integral part of routine doping controls. The breadth of information contained in blood samples has become considerably more accessible for anti-doping purposes over the last 10 years through technological advancements regarding analytical instrumentation as well as enhanced sample collection systems. Particularly, microsampling of whole blood and serum, for instance as dried blood spots (DBS), has opened new avenues in sports drug testing and substantially increased the availability and cost-effectiveness of doping control specimens. Thus, microvolume blood specimens possess the potential to improve monitoring of blood hormone and drug levels, support evaluation of circulating drug concentrations in competition, and enhance the stability of labile markers and target analytes in blood passport analyses as well as peptide hormone and steroid ester detection. Further, the availability of the fraction of lysed erythrocytes for anti-doping purposes warrants additional investigation, considering the sequestering capability of red blood cells (RBCs) for certain substances, as a complementary approach in support of the clean sport.

[1]  L. Ekström,et al.  Optimizing detection of erythropoietin receptor agonists from dried blood spots for anti‐doping application , 2022, Drug testing and analysis.

[2]  D. Eichner,et al.  Growth hormone isoform testing in capillary dried blood spots: results from single and multiple dose administration studies and large-scale field collections. , 2022, Drug Testing and Analysis.

[3]  M. Thevis,et al.  Probing for factors influencing exhaled breath drug testing in sports - pilot studies focusing on the tested individual's tobacco smoking habit and sex. , 2022, Rapid Communications in Mass Spectrometry.

[4]  E. Alladio,et al.  Development and validation of a UHPLC-HRMS-QTOF method for the detection of 132 New Psychoactive Substances and synthetic opioids, including fentanyl, in Dried Blood Spots. , 2022, Talanta.

[5]  Peijie Chen,et al.  Automated online dried blood spot sample preparation and detection of anabolic steroid esters for sports drug testing. , 2022, Drug testing and analysis.

[6]  M. Thevis,et al.  Sports Drug Testing and the Athletes' Exposome. , 2021, Drug Testing and Analysis.

[7]  D. Eichner,et al.  Tracking immature reticulocyte proteins for improved detection of rhEPO abuse. , 2021, American journal of hematology.

[8]  A. Marchand,et al.  A fast screening method for the detection of CERA in dried blood spots , 2021, Drug testing and analysis.

[9]  N. Nordsborg,et al.  No pain, just gain: Painless, easy, and fast Dried Blood Spot collection from fingertip and upper arm in doping control. , 2021, Drug testing and analysis.

[10]  S. Rudaz,et al.  Steroid profiling by UHPLC-MS/MS in dried blood spots collected from healthy women with and without testosterone gel administration. , 2021, Journal of pharmaceutical and biomedical analysis.

[11]  S. Voss,et al.  The use of RNA‐based 5'‐aminolevulinate synthase 2 biomarkers in dried blood spots to detect recombinant human erythropoietin microdoses , 2021, Drug testing and analysis.

[12]  M. Thevis,et al.  Current Insights into the Steroidal Module of the Athlete Biological Passport , 2021, International Journal of Sports Medicine.

[13]  D. Eichner,et al.  Measurement of Immature Reticulocytes in Dried Blood Spots by Mass Spectrometry. , 2021, Clinical Chemistry.

[14]  A. Marchand,et al.  EPO transgene detection in Dried Blood Spots for antidoping application. , 2021, Drug Testing and Analysis.

[15]  W. Weinmann,et al.  Fully Automated Correction for the Hematocrit Bias of Non-Volumetric Dried Blood Spot Phosphatidylethanol Analysis. , 2021, Alcohol.

[16]  N. Nordsborg,et al.  Stability and detectability of testosterone esters in Dried Blood Spots after intramuscular injections. , 2021, Drug testing and analysis.

[17]  M. Thevis,et al.  Do dried blood spots (DBS) have the potential to support result management processes in routine sports drug testing? - Part 2: Proactive sampling for follow-up investigations concerning atypical or adverse analytical findings. , 2021, Drug testing and analysis.

[18]  Christophe Stove,et al.  Alternative Sampling Devices to Collect Dried Blood Microsamples: State-of-the-Art , 2021, Therapeutic drug monitoring.

[19]  Stefan Gaugler,et al.  Fully Automated Optical Hematocrit Measurement From Dried Blood Spots. , 2020, Journal of analytical toxicology.

[20]  M. Luginbühl,et al.  Dried Blood Spots for Anti-Doping: Why Just Going Volumetric May Not Be Sufficient. , 2020, Drug testing and analysis.

[21]  Ó. Pozo,et al.  On the road of dried blood spot sampling for anti-doping tests. Detection of GHRP-2 abuse. , 2020, Drug testing and analysis.

[22]  M. Thevis,et al.  Analysis of cobalt for human sports drug testing purposes using ICP- and LC-ICP-MS. , 2020, Drug Testing and Analysis.

[23]  Y. Daali,et al.  Is pain temporary and glory for ever? Detection of tramadol using dried blood spot in cycling competitions. , 2020, Drug testing and analysis.

[24]  M. Thevis,et al.  Paper spray mass spectrometry - A potential complementary technique for the detection of polar compounds in sports drug testing. , 2020, Drug testing and analysis.

[25]  William Chih-Wei Chang,et al.  Determination of anabolic steroids in dried blood using microsampling and gas chromatography-tandem mass spectrometry: Application to a testosterone gel administration study. , 2020, Journal of chromatography. A.

[26]  N. Nordsborg,et al.  Single-dose administration of clenbuterol is detectable in Dried Blood Spots. , 2020, Drug testing and analysis.

[27]  M. Fedoruk Virtual drug testing: redefining sample collection in a global pandemic , 2020, Bioanalysis.

[28]  J. Segura,et al.  Automation of RNA-based biomarker extraction from dried blood spots for the detection of blood doping. , 2020, Bioanalysis.

[29]  W. Weinmann,et al.  Automated High-Throughput Analysis of Tramadol and O-Desmethyltramadol in Dried Blood Spots. , 2020, Drug testing and analysis.

[30]  M. Thevis,et al.  Fully automated dried blood spot sample preparation enables the detection of lower molecular mass peptide and non-peptide doping agents by means of LC-HRMS , 2020, Analytical and Bioanalytical Chemistry.

[31]  M. Thevis,et al.  Do dried blood spots (DBS) have the potential to support result management processes in routine sports drug testing? , 2020, Drug testing and analysis.

[32]  L. Mercolini,et al.  Blood and Plasma Volumetric Absorptive Microsampling (VAMS) Coupled to LC-MS/MS for the Forensic Assessment of Cocaine Consumption , 2020, Molecules.

[33]  J. McElnay,et al.  Haematocrit, blood volume and surface area of dried blood spots- a quantitative model. , 2020, Drug testing and analysis.

[34]  M. Saugy,et al.  Anti-doping: from health tests to the athlete biological passport. , 2020, Drug testing and analysis.

[35]  M. Saugy,et al.  Detection of Stimulated Erythropoiesis by the RNA-Based 5'-Aminolevulinate Synthase 2 Biomarker in Dried Blood Spot Samples. , 2019, Clinical chemistry.

[36]  Holly D Cox Dried Blood Spots May Improve Detection of Blood Doping. , 2019, Clinical chemistry.

[37]  M. Thevis,et al.  Development of two complementary LC-HRMS methods for analyzing sotatercept in dried blood spots for doping controls. , 2019, Bioanalysis.

[38]  F. Curcio,et al.  A fast, nondestructive, low-cost method for the determination of hematocrit of dried blood spots using image analysis , 2019, Clinical chemistry and laboratory medicine.

[39]  M. Thevis,et al.  SARCOSYL-PAGE: Optimized Protocols for the Separation and Immunological Detection of PEGylated Proteins. , 2018, Methods in molecular biology.

[40]  M. Thevis,et al.  Analysis of insulin and insulin analogs from dried blood spots by means of liquid chromatography-high resolution mass spectrometry. , 2018, Drug testing and analysis.

[41]  R. Ventura,et al.  Detection of erythropoiesis-stimulating agents in a single dried blood spot. , 2018, Drug testing and analysis.

[42]  D. Marshall,et al.  Prediction of haematocrit in dried blood spots from the measurement of haemoglobin using commercially available sodium lauryl sulphate , 2018, Annals of clinical biochemistry.

[43]  G. Gerra,et al.  Determination of oxycodone and its major metabolites in haematic and urinary matrices: Comparison of traditional and miniaturised sampling approaches , 2018, Journal of pharmaceutical and biomedical analysis.

[44]  M. Aalders,et al.  Correction for the Hematocrit Bias in Dried Blood Spot Analysis Using a Nondestructive, Single-Wavelength Reflectance-Based Hematocrit Prediction Method. , 2017, Analytical chemistry.

[45]  M. Thevis,et al.  Screening for adiponectin receptor agonists and their metabolites in urine and dried blood spots , 2017 .

[46]  D. Eichner,et al.  Detection of autologous blood transfusions using a novel dried blood spot method. , 2017, Drug testing and analysis.

[47]  D. Eichner,et al.  Mass Spectrometry Method to Measure Membrane Proteins in Dried Blood Spots for the Detection of Blood Doping Practices in Sport. , 2017, Analytical chemistry.

[48]  M. Farré,et al.  Evaluation of fibronectin 1 in one dried blood spot and in urine after rhGH treatment. , 2017, Drug testing and analysis.

[49]  G. Gerra,et al.  Dried haematic microsamples and LC-MS/MS for the analysis of natural and synthetic cannabinoids. , 2017, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[50]  M. Oostendorp,et al.  Measurement of Hematocrit in Dried Blood Spots Using Near-Infrared Spectroscopy: Robust, Fast, and Nondestructive. , 2016, Clinical chemistry.

[51]  Wilhelm Schänzer,et al.  Sports drug testing using complementary matrices: Advantages and limitations. , 2016, Journal of pharmaceutical and biomedical analysis.

[52]  M. Farré,et al.  Determination of Recent Growth Hormone Abuse Using a Single Dried Blood Spot. , 2016, Clinical chemistry.

[53]  M. Saugy,et al.  Autologous Blood Transfusion in Sports: Emerging Biomarkers. , 2016, Transfusion medicine reviews.

[54]  M. Aalders,et al.  A Novel, Nondestructive, Dried Blood Spot-Based Hematocrit Prediction Method Using Noncontact Diffuse Reflectance Spectroscopy. , 2016, Analytical chemistry.

[55]  L. Mercolini,et al.  LC-MS/MS and volumetric absorptive microsampling for quantitative bioanalysis of cathinone analogues in dried urine, plasma and oral fluid samples. , 2016, Journal of pharmaceutical and biomedical analysis.

[56]  M. Thevis,et al.  Fully automated determination of nicotine and its major metabolites in whole blood by means of a DBS online-SPE LC-HR-MS/MS approach for sports drug testing. , 2016, Journal of pharmaceutical and biomedical analysis.

[57]  M. Thevis,et al.  Analyses of Meldonium (Mildronate) from Blood, Dried Blood Spots (DBS), and Urine Suggest Drug Incorporation into Erythrocytes , 2016, International Journal of Sports Medicine.

[58]  D. Tonoli,et al.  The use of mass spectrometry to analyze dried blood spots. , 2016, Mass spectrometry reviews.

[59]  M. Dohi,et al.  Comparison of urine analysis and dried blood spot analysis for the detection of ephedrine and methylephedrine in doping control. , 2016, Drug testing and analysis.

[60]  J. Henion,et al.  Quantitative determination of opioids in whole blood using fully automated dried blood spot desorption coupled to on-line SPE-LC-MS/MS. , 2016, Drug testing and analysis.

[61]  M. Thevis,et al.  Detection of testosterone esters in blood. , 2015, Drug testing and analysis.

[62]  M. Thevis,et al.  Determination of Synacthen® in dried blood spots for doping control analysis using liquid chromatography tandem mass spectrometry , 2015, Analytical and Bioanalytical Chemistry.

[63]  M. Thevis,et al.  Use of dried blood spots in doping control analysis of anabolic steroid esters. , 2014, Journal of pharmaceutical and biomedical analysis.

[64]  Nicholas E. Manicke,et al.  Paper Spray Ionization for Direct Analysis of Dried Blood Spots , 2014 .

[65]  C. Lundby,et al.  Blood doping: potential of blood and urine sampling to detect autologous transfusion , 2014, British Journal of Sports Medicine.

[66]  R. Chopra,et al.  An activin receptor IIA ligand trap promotes erythropoiesis resulting in a rapid induction of red blood cells and haemoglobin , 2014, British journal of haematology.

[67]  Brooke E. Tvermoes,et al.  Effects and blood concentrations of cobalt after ingestion of 1 mg/d by human volunteers for 90 d. , 2014, The American journal of clinical nutrition.

[68]  M. Thevis,et al.  Mass spectrometric studies on the in vivo metabolism and excretion of SIRT1 activating drugs in rat urine, dried blood spots, and plasma samples for doping control purposes. , 2014, Journal of pharmaceutical and biomedical analysis.

[69]  Donald H Chace,et al.  Microsample analyses via DBS: challenges and opportunities. , 2013, Bioanalysis.

[70]  T. Pottgiesser,et al.  Current strategies of blood doping detection , 2013, Analytical and Bioanalytical Chemistry.

[71]  M. Thevis,et al.  Quantification of AICAR-ribotide concentrations in red blood cells by means of LC-MS/MS , 2013, Analytical and Bioanalytical Chemistry.

[72]  W. Lambert,et al.  Prediction of the hematocrit of dried blood spots via potassium measurement on a routine clinical chemistry analyzer. , 2013, Analytical chemistry.

[73]  D. Eichner,et al.  Quantification of insulin-like growth factor-1 in dried blood spots for detection of growth hormone abuse in sport , 2013, Analytical and Bioanalytical Chemistry.

[74]  M. Bidlingmaier New detection methods of growth hormone and growth factors. , 2012, Endocrine development.

[75]  M. Thevis,et al.  Development and validation of a mass spectrometric detection method of peginesatide in dried blood spots for sports drug testing , 2012, Analytical and Bioanalytical Chemistry.

[76]  M. Thevis,et al.  Sensitive determination of prohibited drugs in dried blood spots (DBS) for doping controls by means of a benchtop quadrupole/Orbitrap mass spectrometer , 2012, Analytical and Bioanalytical Chemistry.

[77]  Patrice Mangin,et al.  Direct analysis of dried blood spots coupled with mass spectrometry: concepts and biomedical applications , 2012, Analytical and Bioanalytical Chemistry.

[78]  M. Thevis,et al.  Dried blood spots (DBS) for doping control analysis , 2011 .

[79]  P. Bennekou,et al.  Cobalt uptake and binding in human red blood cells. , 2011, Blood cells, molecules & diseases.

[80]  C. Buisson,et al.  Simultaneous quantification and qualification of synacthen in plasma , 2011, Analytical and bioanalytical chemistry.

[81]  Neil Spooner,et al.  The effect of hematocrit on assay bias when using DBS samples for the quantitative bioanalysis of drugs. , 2010, Bioanalysis.

[82]  P. Abu-Rabie,et al.  Direct quantitative bioanalysis of drugs in dried blood spot samples using a thin-layer chromatography mass spectrometer interface. , 2009, Analytical chemistry.

[83]  N. Robinson,et al.  The fight against doping: back on track with blood. , 2009, Drug testing and analysis.

[84]  G. V. Van Berkel,et al.  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. , 2009, Analytical chemistry.

[85]  M. Thevis,et al.  Determination of Synacthen in urine for sports drug testing by means of nano-ultra-performance liquid chromatography/tandem mass spectrometry. , 2009, Rapid communications in mass spectrometry : RCM.

[86]  G. V. Van Berkel,et al.  High-throughput mode liquid microjunction surface sampling probe. , 2009, Analytical chemistry.

[87]  Aurélien Thomas,et al.  On-line desorption of dried blood spot: A novel approach for the direct LC/MS analysis of micro-whole blood samples. , 2009, Journal of pharmaceutical and biomedical analysis.

[88]  A. Bergmann,et al.  High-sensitivity chemiluminescence immunoassays for detection of growth hormone doping in sports. , 2009, Clinical chemistry.

[89]  Mats Ehmebo DRUG BINDING TO BLOOD CELLS , 2009 .

[90]  Wilhelm Schänzer,et al.  Factors influencing the steroid profile in doping control analysis. , 2008, Journal of mass spectrometry : JMS.

[91]  P. Sönksen,et al.  Detection of growth hormone abuse in sport. , 2007, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[92]  Frederick C W Wu,et al.  Drug Insight: testosterone preparations , 2006, Nature Clinical Practice Urology.

[93]  Zheng Ouyang,et al.  Ambient Mass Spectrometry , 2006, Science.

[94]  Zheng Ouyang,et al.  Detection Technologies. Ambient mass spectrometry. , 2006, Science.

[95]  H. Luftmann A simple device for the extraction of TLC spots: direct coupling with an electrospray mass spectrometer , 2004, Analytical and bioanalytical chemistry.

[96]  B. Exer,et al.  Über die Hemmung der Carboanhydratase durch Saluretica , 2004, Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie.

[97]  M. Farré,et al.  Oral testosterone administration detected by testosterone glucuronidation measured in blood spots dried on filter paper. , 2000, Clinical chemistry.

[98]  J. Segura,et al.  Detection of testosterone esters in human plasma , 1995 .

[99]  R. Dixon,et al.  Acadesine (AICA‐Riboside): Disposition and Metabolism of an Adenosine‐Regulating Agent , 1993, Journal of clinical pharmacology.

[100]  H. Gruber,et al.  AICA‐Riboside: Safety, Tolerance, and Pharmacokinetics of a Novel Adenosine‐Regulating Agent , 1991, Journal of clinical pharmacology.

[101]  Henny H. Billett,et al.  Hemoglobin and Hematocrit , 1990 .

[102]  H. Nakahama,et al.  Binding of hydrochlorothiazide to erythrocytes. , 1989, Journal of pharmacobio-dynamics.

[103]  S. Wallace,et al.  Uptake of acetazolamide by human erythrocytes in vitro. , 1977, Journal of pharmaceutical sciences.

[104]  K. Hellström,et al.  Binding‐site interaction of chlorthalidone and acetazolamide, two drugs transported by red blood cells , 1975, Clinical pharmacology and therapeutics.

[105]  M. Ehrnebo,et al.  Binding of (+)‐ and (‐)‐Δ1‐tetrahydrocannabinols and (‐)‐7‐hydroxy‐Δ1‐tetrahydrocannabinol to blood cells and plasma proteins in man , 1974 .

[106]  M. Ehrnebo,et al.  Binding of (+)- and (minus)-delta-1-tetrahydrocannabinols and (minus)-7-hydroxy-delta-1-tetrahydrocannabinol to blood cells and plasma proteins in man. , 1974, The Journal of pharmacy and pharmacology.

[107]  R. Guthrie,et al.  A SIMPLE PHENYLALANINE METHOD FOR DETECTING PHENYLKETONURIA IN LARGE POPULATIONS OF NEWBORN INFANTS. , 1963, Pediatrics.

[108]  T. Maren,et al.  The binding of aromatic sulfonamides to erythrocytes. , 1961, Biochemical pharmacology.

[109]  E. Goldwasser,et al.  Studies on erythropoiesis. V. The effect of cobalt on the production of erythropoietin. , 1958, Blood.