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

Author:

Jonsson Ove1,Steffen Ann-Charlott2,Sundquist Valentina Screpanti2,Janson Juliette3,Martinsson Stefan2,Määttä Ulrika2,Emanuelsson Anna Breitholtz3

Affiliation:

1. Global DMPK, In Vivo Screening & Profiling, AstraZeneca R&D, SE-15185, Södertälje, Sweden.

2. Global DMPK, In Vivo Screening & Profiling, AstraZeneca R&D, SE-15185, Södertälje, Sweden

3. iMed CNS & Pain, DMPK, AstraZeneca R&D, SE-15185, Södertälje, Sweden

Abstract

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.

Publisher

Future Science Ltd

Subject

Medical Laboratory Technology,Clinical Biochemistry,General Pharmacology, Toxicology and Pharmaceutics,General Medicine,Analytical Chemistry

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