Capillary microsampling and analysis of 4-ul blood, plasma and serum samples to determine human α-synuclein elimination rate in mice

Background: The capillary microsampling technique was scaled down to enable repeated PK sampling of blood, plasma and serum from mice for the determination of the 14-kDa protein α-synuclein using the Gyrolab™ immunoassay platform. Results: 4-µl plasma, serum or blood samples were taken from 36 mice, in total 648 samples were successfully collected and analyzed. Following intravenous administration of human α-synuclein to mice, the elimination of α-synuclein was rapid, with a half-life in plasma of 1.1 h. High endogenous levels in red blood cells in combination with some hemolysis led to a challenge in the evaluation of α-synuclein exposure in plasma and serum. Conclusion: The small sample volumes and flexibility in choice of liquid matrices using the capillary microsampling technique enable repeated sampling in mouse studies, as well as multi-matrix analysis if needed. Liquid microsampling is well suited for micro- and nano-liter scale immunoassays.

In studies with small laboratory animals such as rats and mice, the lowering of blood volumes collected for the determination of circulating drug or biomarker concentrations is key to animal number reduction and refinement of sampling procedures. Reduced sample volumes also enable new study designs that have the potential to increase the scientific value of the studies, for example, by better correlation between toxicological or pharmacological readouts and exposure. Considering that the bodyweight and circulating blood volume in a mouse is typically only one tenth of that in a rat [1], repeated bleeding for exposure evaluation in mouse studies is particularly challenging. One versatile approach to collect these small microsamples is the capillary microsampling (CMS) technique.

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