Adverse analytical finding due to red blood cells transfusion: A rare case involving the diuretic dorzolamide

Abstract

Early November 2020 an Olympic gold medal winner returned during an out‐competition control an adverse analytical finding for dorzolamide, a diuretic mostly used to treat glaucoma. Estimated urine concentrations were 2.2 and 1.6 ng/ml in the A and B specimens, respectively. As the athlete denied any use of dorzolamide, a complex forensic investigation was suggested. It revealed that the athlete was severely injured during a car crash 6 months before where he received 2× 500 ml of red blood cells transfusion. One of the blood donors declared using dorzolamide. A plasma aliquot, stored for legal purposes, was tested by LC‐MS/MS several months later and contained 4.3 ng/ml of dorzolamide. Given the very long half‐life of the drug, up to 150 days and its reported incorporation into erythrocyte, it was accepted by the French antidoping administration (AFLD) that the source of contamination was this blood transfusion and that the antidoping rule violation was unintended.

The criminal liability of health care professionals treating anabolic steroid users under the SpoPA

“…While WADA regulates thresholds for certain substances [46], such limitations are nowhere to be found under the SpoPA [47, 48]. Miniscule traces of substances given to an athlete via blood transfusions six months ago can still amount to a violation of the anti-doping rules [49]. For national criminal law, the abstract threshold for a violation should be increased and not simply copied from a private disciplinary system.…”

Annual banned‐substance review—Analytical approaches in human sports drug testing 2021/2022–

“…In such cases, testing for seminal fluid‐specific proteins in urine would add critical information as to the plausibility of this scenario, accommodated by immunological and/or chromatographic–mass spectrometric methods, 121 and to which level urine contamination into seminal fluid can affect hypothesized situations was identified as another aspect to properly investigate 122 . Moreover, the unexpected occurrence of an AAF due to a medically required blood transfusion to an athlete 6 months prior to the conducted doping control sample collection by follow‐up investigations 123 underlined the complexity as well as the importance of data‐driven result management, which requires continued high‐quality anti‐doping research. Key aspects of this review that has considered literature published between October 2021 and September 2022 are summarized in the info box in Figure 2.…”

Mass spectrometry in sports drug testing—Analytical approaches and the athletes' exposome

“…In a very recent case, an athlete's exposure to the carbonic anhydrase inhibitor dorzolamide, a diuretic prohibited at-all-times if not ophthalmic topically used, was debated. 66 Here, an accident requiring hospitalization, surgery, and concomitant blood transfusion was reported, where the transfused blood was identified as the source of dorzolamide residues as proven by follow-up analyses of retained plasma aliquots, a scenario that cannot be excluded considering earlier studies on drugs in donor blood. 67 Further, pharmaceutical manufacturing is governed by strict quality controls, and contaminations are even more unexpected to occur; however, the potential for contamination has presumably increased by a continuously growing complexity of generic pharmaceutical supply chains, where the aforementioned quality controls and manufacturing practices might not be fully guaranteed.…”

“…Such guidance has been urgently needed considering the fact that (in contrast to dietary supplements) medications are rarely optional and cannot always be avoided, particularly when injuries and conditions necessitate treatment. In a very recent case, an athlete's exposure to the carbonic anhydrase inhibitor dorzolamide, a diuretic prohibited at‐all‐times if not ophthalmic topically used, was debated 66 . Here, an accident requiring hospitalization, surgery, and concomitant blood transfusion was reported, where the transfused blood was identified as the source of dorzolamide residues as proven by follow‐up analyses of retained plasma aliquots, a scenario that cannot be excluded considering earlier studies on drugs in donor blood 67 .…”