Stressing the limits of capillary blood in anti-doping analysis: perspectives on alkylamine-like stimulants and carbonic anhydrase II inhibitors in result management

The establishment of an anti-doping rule violation extends beyond the mere detection of a prohibited substance. Current interpretation criteria rely primarily on urinary concentration estimates, which may be misleading due to high interindividual variability or pharmacokinetics characteristics of doping agents. This study investigates the potential of capillary blood collected through volumetric absorptive microsampling (VAMS) as a complementary matrix to urine for supporting results management in doping control. Comparative concentration-time profiling in urine and capillary blood was performed using isometheptene, a stimulant subject to minimum reporting limits (MRLs), and the carbonic anhydrase II inhibitors dorzolamide and brinzolamide as model compounds. For isometheptene, capillary blood detection closely mirrored urinary findings at early time points but exhibited a markedly shorter detection window, supporting improved discrimination between in-competition and out-of-competition administration in cases where urinary concentrations alone may lead to ambiguous interpretation. In contrast, for the long-lasting diuretics brinzolamide and dorzolamide, urinary concentrations showed limited interpretative value, whereas capillary blood analysis provided more consistent detectability, reflecting their strong affinity for red blood cells. However, capillary blood concentrations did not allow unequivocal discrimination between permitted ophthalmic use and prohibited administration routes. Overall, these findings demonstrate that capillary blood analysis can enhance interpretative context of anti-doping result management, particularly for substances with complex pharmacokinetics, and provide a scientific basis for the future establishment of blood-based reporting criteria.