Analysis of cobalt for human sports drug testing purposes using ICP- and LC-ICP-MS.

Due to the current demands in the fight against manipulation of blood and blood components, commonly referred to as "blood doping" in sports drug testing, specific and sensitive detection methods enabling the detection of prohibited substances and methods of doping are required. Similar to illicit blood transfusions, erythropoiesis stimulating agents have been shown to be misused in sport, aiming at improving an athlete's aerobic capacity and endurance performance. Amongst other strategies, the administration of ionic cobalt (Co2+ ) can increase the number of erythrocytes by stimulating the endogenous erythropoietin (EPO) biosynthesis. Conversely, several organic Co-containing compounds such as e.g. cyanocobalamin (vitamin B12) are not prohibited in sports, and thus an analytical differentiation of permitted and banned contributions to urinary Co-concentrations are desirable. An excretion study with daily applications of either 1 mg of CoCl2 or 1 mg of cyanocobalamin was conducted with 20 volunteers over a period of 14 consecutive days. Urine, plasma, and concentrated red blood cells were analyzed for their cobalt content. The samples were collected starting 7 days before the administration until 7 days after. Total Co concentrations were analyzed by using inductively-coupled plasma mass spectrometry (ICP-MS), which yielded significantly elevated levels exclusively after inorganic cobalt intake. Furthermore, a liquid chromatography (LC)-ICP-MS approach was established and employed for the simultaneous determination of organically bound and inorganic cobalt by chromatographic separation within one single run. The analytical approach offers the option to further develop detection methods of illegal Co2+ supplementation in sport.

[1]  M. Thevis,et al.  Elevated urinary cobalt concentrations identified in routine doping controls can originate from vitamin B12. , 2019, Rapid communications in mass spectrometry : RCM.

[2]  Shiuh-Jen Jiang,et al.  Determination of cobalt compounds in dietary supplements using liquid chromatography inductively coupled plasma mass spectrometry , 2019, Spectrochimica Acta Part B: Atomic Spectroscopy.

[3]  M. Thevis,et al.  Erythropoietic effects of low-dose cobalt application. , 2018, Drug testing and analysis.

[4]  B. Gessner,et al.  A Systematic Review of Systemic Cobaltism After Wear or Corrosion of Chrome-Cobalt Hip Implants , 2015, Journal of patient safety.

[5]  Ross G. Wenzel,et al.  Determination of vitamin B12 in equine urine by liquid chromatography - inductively coupled plasma - mass spectrometry. , 2018, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[6]  M. Thevis,et al.  Effects of 3 Weeks of Oral Low-Dose Cobalt on Hemoglobin Mass and Aerobic Performance , 2018, Front. Physiol..

[7]  Benoit Nemery,et al.  Sustainability of artisanal mining of cobalt in DR Congo , 2018, Nature Sustainability.

[8]  T. Wan,et al.  Interlaboratory trial for the measurement of total cobalt in equine urine and plasma by ICP-MS. , 2017, Drug testing and analysis.

[9]  M. Thevis,et al.  Solutions Advertised as Erythropoiesis-stimulating Products were Found to Contain Undeclared Cobalt and Nickel Species , 2016, International Journal of Sports Medicine.

[10]  M. Thevis,et al.  Quantifying cobalt in doping control urine samples--a pilot study. , 2014, Drug testing and analysis.

[11]  W. Jelkmann,et al.  Intolerability of cobalt salt as erythropoietic agent. , 2014, Drug testing and analysis.

[12]  John E. Schiel,et al.  A simple and sensitive LC-ICP-MS method for the accurate determination of vitamin B12 in fortified breakfast cereals and multivitamin tablets , 2013 .

[13]  D. Paustenbach,et al.  Derivation of a chronic oral reference dose for cobalt. , 2012, Regulatory toxicology and pharmacology : RTP.

[14]  M. Thevis,et al.  Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis-stimulating agents in current and preventive doping analysis. , 2012, Drug testing and analysis.

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

[16]  Benoit Nemery,et al.  High human exposure to cobalt and other metals in Katanga, a mining area of the Democratic Republic of Congo. , 2009, Environmental research.

[17]  T. Orsière,et al.  Assessment of occupational exposure to welding fumes by inductively coupled plasma‐mass spectroscopy and by the alkaline Comet assay , 2006, Environmental and molecular mutagenesis.

[18]  G. Lippi,et al.  Cobalt chloride administration in athletes: a new perspective in blood doping? , 2005, British Journal of Sports Medicine.

[19]  N. J. Miller-Ihli,et al.  Cobalamin speciation using reversed-phase micro-high-performance liquid chromatography interfaced to inductively coupled plasma mass spectrometry , 2004 .

[20]  F. Lasne,et al.  Abuse of recombinant erythropoietins by athletes , 2003 .

[21]  D. E. Carter,et al.  Disposition, toxicity, and intestinal absorption of cobaltous chloride in male Fischer 344 rats. , 1999, Journal of toxicology and environmental health. Part A.

[22]  J. Davis,et al.  Experimental Production of Polycythemia in Humans by Administration of Cobalt Chloride , 1958, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

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