Do dried blood spots 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

Abstract Background: Blood sampling is not a common practice for sports drug testing. Our aim was to investigate whether dried blood spots on filter paper could be an alternative to plasma samples for monitoring steroid profiles in dope testing. Methods: We collected dried blood spots and plasma from six healthy Caucasian subjects after an oral 120-mg dose of testosterone undecanoate (TU). Nonconjugated testosterone, testosterone glucuronide (TG), androsterone glucuronide (AG), and etiocholanolone glucuronide (EtG) were measured by gas chromatography–mass spectrometry in both matrices. 17α-Hydroxyprogesterone (17αOHP) and luteinizing hormone (LH) also were measured in the plasma samples. For comparison, similar measurements were done on samples obtained from the same subjects given 25 mg of testosterone propionate (TP) plus 110 mg of testosterone enanthate (TE) intramuscularly after a wash-out period. Results: After oral TU intake, TG, AG, and EtG increased sharply, whereas nonconjugated testosterone did not change significantly. Results on dried blood spots correlated well with those on plasma. The TG/testosterone ratio in blood or plasma was verified to be a sensitive and specific marker (significantly increased for up to 8 h after intake; P <0.05) for oral TU intake but not for intramuscular administration of TP plus TE. Little suppression of plasma LH and 17αOHP was observed after a single oral dose of TU. One subject did not show a significant increase of blood TG after oral TU intake. Conclusions: The measurement of glucuronide conjugates in blood and plasma samples is relevant for sports drug testing when analyzing the steroid profile. Dried blood spots collected on filter paper are a suitable alternative to plasma for detecting testosterone abuse.

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Development and validation of a mass spectrometric detection method of peginesatide in dried blood spots for sports drug testing

Analytical and Bioanalytical Chemistry ◽

10.1007/s00216-012-6043-2 ◽

2012 ◽

Vol 403 (9) ◽

pp. 2715-2724 ◽

Cited By ~ 47

Author(s):

Ines Möller ◽

Andreas Thomas ◽

Hans Geyer ◽

Wilhelm Schänzer ◽

Mario Thevis

Keyword(s):

Drug Testing ◽

Detection Method ◽

Dried Blood Spots ◽

Mass Spectrometric ◽

Mass Spectrometric Detection ◽

Blood Spots ◽

Sports Drug Testing ◽

Development And Validation

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Newborn Screening for Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase and Mitochondrial Trifunctional Protein Deficiencies Using Acylcarnitines Measurement in Dried Blood Spots—A Systematic Review of Test Accuracy

Frontiers in Pediatrics ◽

10.3389/fped.2021.606194 ◽

2021 ◽

Vol 9 ◽

Author(s):

Chris Stinton ◽

Hannah Fraser ◽

Julia Geppert ◽

Rebecca Johnson ◽

Martin Connock ◽

...

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Dried Blood Spots ◽

Test Accuracy ◽

Tandem Mass ◽

Blood Spots ◽

Hydroxyacyl Coa Dehydrogenase ◽

Sensitivity Specificity ◽

Long Chain

Background: Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiencies are rare autosomal recessive fatty acid β-oxidation disorders. Their clinical presentations are variable, and premature death is common. They are included in newborn blood spot screening programs in many countries around the world. The current process of screening, through the measurement of acylcarnitines (a metabolic by-product) in dried blood spots with tandem mass spectrometry, is subject to uncertainty regarding test accuracy.Methods: We conducted a systematic review of literature published up to 19th June 2018. We included studies that investigated newborn screening for LCHAD or MTP deficiencies by tandem mass spectrometry of acylcarnitines in dried blood spots. The reference standards were urine organic acids, blood acylcarnitine profiles, enzyme analysis in cultured fibroblasts or lymphocytes, mutation analysis, or at least 10-year follow-up. The outcomes of interest were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Assessment of titles, abstracts, and full-text papers and quality appraisal were carried out independently by two reviewers. One reviewer extracted study data. This was checked by a second reviewer.Results: Ten studies provided data on test accuracy. LCHAD or MTP deficiencies were identified in 23 babies. No cases of LCHAD/MTP deficiencies were identified in four studies. PPV ranged from 0% (zero true positives and 28 false positives from 276,565 babies screened) to 100% (13 true positives and zero false positives from 2,037,824 babies screened). Sensitivity, specificity, and NPV could not be calculated as there was no systematic follow-up of babies who screened negative.Conclusions: Test accuracy estimates of screening for LCHAD and MTP deficiencies with tandem mass spectrometry measurement of acylcarnitines in dried blood were variable in terms of PPVs. Screening methods (including markers and thresholds) varied between studies, and sensitivity, specificity, and NPVs are unknown.

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Dried blood spots (DBS) in doping controls: a complementary matrix for improved in- and out-of-competition sports drug testing strategies

Analytical Methods ◽

10.1039/c5ay01514f ◽

2015 ◽

Vol 7 (18) ◽

pp. 7596-7605 ◽

Cited By ~ 9

Author(s):

Laura Tretzel ◽

Andreas Thomas ◽

Hans Geyer ◽

Valentin Pop ◽

Wilhelm Schänzer ◽

...

Keyword(s):

Cost Efficiency ◽

Drug Testing ◽

State Of The Art ◽

Analytical Techniques ◽

Dried Blood Spots ◽

Sample Collection ◽

Blood Spots ◽

Testing Strategies ◽

In Doping ◽

Efficiency Test

The use of dried blood spots as a complementary sample matrix combined with state-of-the-art analytical techniques substantially improves doping control efforts, particularly concerning cost-efficiency, test frequency, and sample collection invasiveness.

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Application of oral fluid and dried blood spots as a matrix for roadside drug testing

New Sampling Strategies in Toxicology and Therapeutic Drug Monitoring ◽

10.4155/fseb2013.14.305 ◽

2015 ◽

pp. 94-109 ◽

Cited By ~ 1

Author(s):

Sarah MR Wille ◽

Ann-Sofie ME Ingels ◽

Nele Samyn

Keyword(s):

Drug Testing ◽

Oral Fluid ◽

Dried Blood Spots ◽

Blood Spots

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Storing Newborn Blood Spots: Modern Controversies

The Journal of Law Medicine & Ethics ◽

10.1111/j.1748-720x.2004.tb01979.x ◽

2004 ◽

Vol 32 (4) ◽

pp. 741-748 ◽

Cited By ~ 15

Author(s):

Linda Kharaboyan ◽

Denise Avard ◽

Bartha Maria Knoppers

Keyword(s):

Newborn Screening ◽

Diagnostic Test ◽

Clinical Data ◽

Dried Blood Spots ◽

Parental Consent ◽

Public Attention ◽

Screening Programs ◽

Blood Spots ◽

Blood Spot

Though in existence for over thirty-five years, due to the increasing panoply of possible tests. Newborn screening programs are drawing public attention. Many jurisdictions have mandatory newborn screening programs for treatable disorders. Disorders are detected through tests on blood spots drawn from a newborn’s heel soon after birth and verified through a diagnostic test with follow-up. Unbeknownst to most parents, these blood spot cards are also stored thereafter. Indeed, while dried blood spots (DBSs) are primarily used for screening for health problems, experience demonstrates that they can be made useful in various contexts unrelated to screening.Newborn dried blood spots have taken on a new life as a result of developments in genetics and the increasing ability of bioinformatics to link DNA information with clinical data. Additionally, storage and secondary uses have been documented to occur without parental consent.

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Frequency and Predictors of Tenofovir-diphosphate Detection Among Young Kenyan Women in a Real-world Pre-exposure Prophylaxis Implementation Program

Clinical Infectious Diseases ◽

10.1093/cid/ciaa181 ◽

2020 ◽

Vol 71 (9) ◽

pp. e509-e512 ◽

Cited By ~ 1

Author(s):

Jillian Pintye ◽

John Kinuthia ◽

Felix Abuna ◽

Kenneth Mugwanya ◽

Harison Lagat ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Real World ◽

Dried Blood Spots ◽

Blood Spots ◽

Implementation Program ◽

Immunodeficiency Virus ◽

Kenyan Women ◽

Exposure Prophylaxis ◽

Tenofovir Diphosphate

Abstract In a pre-exposure prophylaxis program for Kenyan women, we detected tenofovir-diphosphate in 61% (125/201) of randomly selected dried blood spots collected at the first follow-up visit. Tenofovir-diphosphate was detected more frequently among women who had partners living with human immunodeficiency virus, who were not pregnant, and who were ≥24 years.

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Dietary Supplement and Food Contaminations and Their Implications for Doping Controls

Foods ◽

10.3390/foods9081012 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1012 ◽

Cited By ~ 2

Author(s):

Katja Walpurgis ◽

Andreas Thomas ◽

Hans Geyer ◽

Ute Mareck ◽

Mario Thevis

Keyword(s):

Dietary Supplements ◽

Drug Testing ◽

Analytical Data ◽

Good Manufacturing Practice ◽

Therapeutic Drug ◽

Positive Effects ◽

Sports Drug Testing ◽

And Performance ◽

Androgenic Steroids ◽

Result Management

A narrative review with an overall aim of indicating the current state of knowledge and the relevance concerning food and supplement contamination and/or adulteration with doping agents and the respective implications for sports drug testing is presented. The identification of a doping agent (or its metabolite) in sports drug testing samples constitutes a violation of the anti-doping rules defined by the World Anti-Doping Agency. Reasons for such Adverse Analytical Findings (AAFs) include the intentional misuse of performance-enhancing/banned drugs; however, also the scenario of inadvertent administrations of doping agents was proven in the past, caused by, amongst others, the ingestion of contaminated dietary supplements, drugs, or food. Even though controversial positions concerning the effectiveness of dietary supplements in healthy subjects exist, they are frequently used by athletes, anticipating positive effects on health, recovery, and performance. However, most supplement users are unaware of the fact that the administration of such products can be associated with unforeseeable health risks and AAFs in sports. In particular anabolic androgenic steroids (AAS) and stimulants have been frequently found as undeclared ingredients of dietary supplements, either as a result of cross-contaminations due to substandard manufacturing practices and missing quality controls or an intentional admixture to increase the effectiveness of the preparations. Cross-contaminations were also found to affect therapeutic drug preparations. While the sensitivity of assays employed to test pharmaceuticals for impurities is in accordance with good manufacturing practice guidelines allowing to exclude any physiological effects, minute trace amounts of contaminating compounds can still result in positive doping tests. In addition, food was found to be a potential source of unintentional doping, the most prominent example being meat tainted with the anabolic agent clenbuterol. The athletes’ compliance with anti-doping rules is frequently tested by routine doping controls. Different measures including offers of topical information and education of the athletes as well as the maintenance of databases summarizing low- or high-risk supplements are important cornerstones in preventing unintentional anti-doping rule violations. Further, the collection of additional analytical data has been shown to allow for supporting result management processes.

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