Dried blood spots for anti‐doping: Why just going volumetric may not be sufficient

Embossed Paper Platform for Whole Blood Collection, Room Temperature Storage, and Direct Analysis by Pinhole Paper Spray Mass Spectrometry

“…Such issues reduce quantitative accuracy and precision, which are important for disease monitoring. 23 To improve upon conventional DBS sampling, pre-cut DBS has been developed to analyze a set volume of the sample. 24 By analyzing the entire sample spot, the hematocrit and chromatographic effects are eliminated.…”

“…This results in inconsistent sampling, where the amount of the analyte in a sample can drastically vary from spot to spot. Such issues reduce quantitative accuracy and precision, which are important for disease monitoring . To improve upon conventional DBS sampling, pre-cut DBS has been developed to analyze a set volume of the sample .…”

Performance‐enhancing drugs and the Olympics

“…Compared with venipuncture, DBS is less invasive and does not require a phlebotomist or strict temperature control [19]. Nevertheless, DBS is limited by small volumes and hematocrit-dependent variations in viscosity that affect test reliability [19,20]. Imple-mentation of Olympic DBS testing has been slated for the 2022 Games; [20] however, the USADA started trialing DBS in 2020.…”

“…Nevertheless, DBS is limited by small volumes and hematocrit-dependent variations in viscosity that affect test reliability [19,20]. Imple-mentation of Olympic DBS testing has been slated for the 2022 Games; [20] however, the USADA started trialing DBS in 2020. DBS may augment current testing, but its limitations make it unlikely to replace venipuncture and urinalysis.…”

UHPLC–HRMS Method for the Simultaneous Screening of 235 Drugs in Capillary Blood for Doping Control Purpose: Comparative Evaluation of Volumetric and Non-volumetric Dried Blood Spotting Devices

“…Dried blood spots (DBSs) are a form of bio-samples in which capillary blood by fingertip or arm pricking is applied onto marked circles on untreated/treated cellulose paper or adsorbed on specially manufactured volumetrically controlled polymer-based tips or dots. − Since its introduction, the use of DBS, as an alternative matrix, has been progressively extending, now covering many different applications, including therapeutic drug monitoring, forensic analysis, and, more recently, doping analysis. − Indeed, DBS provide several advantages compared to conventional venous blood samples: (i) the procedure for the collection of the sample is simplified and minimally invasive, so that it can be successfully performed even by minimally trained personnel, (ii) it offers favorable stability of many analytes, (iii) the collection process reduces the risk of infection, (iv) the risk of bacterial contamination or hemolysis is minimal, (v) the collection devices are generally low cost; and finally (vi) the storage and transport of samples are easier and without additional costs associated with the need of ensuring a rigid temperature control along the chain of custody. ,, Nonetheless, different challenges also need to be faced when DBSs are used and primarily among them are as follows: (i) to ensure a sufficient quality of the spot (mainly in terms of size and homogeneity), (ii) to allow a satisfying recovery of all the target analytes in the case of multi-targeted assays, a critical parameter given the reduced available volume of the sample, (iii) to assess the relevance of hematocrit effects, possibly influencing the analyte concentration and recovery in the case of quantitative determinations, (iv) to take into account the blood-to-plasma ratio (that provides an indication of the binding to erythrocytes of the target analytes), (v) to optimize the timing and procedure for the addition of the internal standard, indispensable in the case of quantitative determinations, (vi) to avoid the loss of volatile or photodegradable analytes, and finally (vii) to specifically consider the effects on the integrity of the sample of environmental conditions, primarily humidity and bacterial growth. ,,− For the above reasons, different countermeasures were proposed, including (i) the use of plastic bags containing adequate desiccants (i.e., silica gel and bentonite) and humidity indicators, (ii) the use of calibrated capillaries and of volumetric microsampling devices, in the aim to increase the repeatability and reproducibility of the spots, (iii) the use of dried plasma spots (DPSs), in order to overcome multiple hematocrit effects and plasma-to-blood ratio issues, and finally (iv) the measurement of hematocrit directly on the DBS cards to control multiple hematocrit effects. − …”