Quantifying cobalt in doping control urine samples – a pilot study

Abstract

Since first reports on the impact of metals such as manganese and cobalt on erythropoiesis were published in the late 1920s, cobaltous chloride became a viable though not widespread means for the treatment of anaemic conditions. Today, its use is de facto eliminated from clinical practice; however, its (mis)use in human as well as animal sport as an erythropoiesis-stimulating agent has been discussed frequently. In order to assess possible analytical options and to provide relevant information on the prevalence of cobalt use/misuse among athletes, urinary cobalt concentrations were determined by inductively coupled plasma-mass spectrometry (ICP-MS) from four groups of subjects. The cohorts consisted of (1) a reference population with specimens of 100 non-elite athletes (not being part of the doping control system), (2) a total of 96 doping control samples from endurance sport athletes, (3) elimination study urine samples collected from six individuals having ingested cobaltous chloride (500 µg/day) through dietary supplements, and (4) samples from people supplementing vitamin B12 (cobalamin) at 500 µg/day, accounting for approximately 22 µg of cobalt. The obtained results demonstrated that urinary cobalt concentrations of the reference population as well as the group of elite athletes were within normal ranges (0.1-2.2 ng/mL). A modest but significant difference between these two groups was observed (Wilcoxon rank sum test, p < 0.01) with the athletes' samples presenting slightly higher urinary cobalt levels. The elimination study urine specimens yielded cobalt concentrations between 40 and 318 ng/mL during the first 6 h post-administration, and levels remained elevated (>22 ng/mL) up to 33 h. Oral supplementation of 500 µg of cobalamin did not result in urinary cobalt concentrations > 2 ng/mL. Based on these pilot study data it is concluded that measuring the urinary concentration of cobalt can provide information indicating the use of cobaltous chloride by athletes. Additional studies are however required to elucidate further factors potentially influencing urinary cobalt levels.

Erythropoietic effects of low‐dose cobalt application

“…The time course of urinary Co 2+ excretion after a single oral application, with maximum values 3–7 hours after ingestion and 50‐fold elevated values even at 24 hours, is in accordance with data from the literature . The elimination half‐life of Co 2+ after low‐dose oral ingestion is between 4 and 12 hours .…”

“…The blood samples were taken after the subject was left for at least 15 minutes in a sitting position, and the samples were transported under monitored cooled conditions within the following 24 hours to the WADA‐accredited Institute of Doping Analysis und Sports Biochemistry in Dresden, Germany. The urine samples were also transported under the described standardized conditions to the Institute of Biochemistry of the German Sport University, Cologne, Germany, and were stored at −80°C until they were analyzed as follows . All samples were subjected to an EN ISO 17294‐accredited test method for the quantitative determination of cobalt in aqueous and urinary matrix using inductively coupled plasma mass spectrometry (ICP–MS).…”

Elevated urinary cobalt concentrations identified in routine doping controls can originate from vitamin B12

“…In June 2019, a routine doping control urine sample was tested for cobalt and returned an atypically high level of cobalt of 24.3 ng/mL, which was neither in agreement with pilot study data on a small number of athletes nor did the tested individual belong to a specific subgroup of the aforementioned categories that occupationally tend to present elevated urinary cobalt concentrations. Therefore, follow‐up studies aiming at differentiating inorganic and organically bound cobalt were initiated.…”

“…To date, doping control urine samples are commonly analyzed for total cobalt concentrations by means of inductively coupled plasma mass spectrometry (ICP‐MS). Although no threshold or reporting level has yet been established above which urinary cobalt concentrations are to be considered as an adverse analytical finding, urinary reference concentrations were reported to range between 0.1 and 2 ng/mL . Exceptionally high levels were found in urine samples of miners and inhabitants of the immediate environment of cobalt mines and workers of hard metal factories .…”

Commentary on Paper: “Controlling the misuse of cobalt in horses”

“…This paper makes only a fleeting reference to the 'so called "cobalt unit"', and in turn cites earlier references to work on starved rats. [13] The only published work in horses is that of [14] where after a single administration of 109 milligrams of cobalt chloride to each of 16 horses, they observed NO increase in red cells or erythropoietin. While the motivation of racing authorities in controlling any violation of animal welfare is unquestioned, it must be recognized that toxic effects can be demonstrated for almost any substance, including sodium chloride and water.…”