Validation of A Bioanalytical Method Using Capillary Microsampling of 8 µL Plasma Samples: Application to A Toxicokinetic Study in Mice

Abstract

It is shown that 8 µl plasma microsamples can be sampled and analyzed with consistently excellent accuracy and precision. Capillary microsampling of plasma offers a possibility to combine ethical, scientific and economic benefits while still maintaining the advantage of having drug exposure data in plasma.

A Dried Blood Spot Update: Still an Important Bioanalytical Technique?

“…Furthermore, it has brought to the forefront, considerations on the 3Rs and ethics in animal use. This has helped to facilitate the inves tigation and implementation of micro sampling in various forms for preclinical studies, with wet and dry blood, and plasma samples being discussed, resulting in notable reductions in the number of rodents required and reductions in blood volumes taken from a given animal [39][40][41]. In turn, this has brought together bioanalytical scientists and their toxicology and animal technician colleagues with a common purpose.…”

Incorporation of capillary microsampling into whole body plethysmography and modified Irwin safety pharmacology studies in rats

“…Furthermore, the provision of pharmacokinetic data from the same animal as the functional, toxicological or histopathological endpoints provides additional scientific robustness and allows interpretation of individual data as part of the overall interpretation of results (as is the case in non-rodent studies). This technique has been successfully implemented in both mouse (Jonsson et al, 2012b;Wan et al, 2012) and rat (Jonsson et al, 2012a) toxicokinetic and general toxicology studies, whilst its application in paediatric clinical studies highlights how this technology can also improve both the data and the experience for children in these settings (Jackson-Addie et al, 2012).…”

“…Following a short period in a warming chamber and minimal handling, blood volumes as low as 25e32 ml are accurately collected (Jonsson et al, 2012a(Jonsson et al, , 2012b, and as such, the impact on the animal, both in terms of welfare and on volumedepletion effects on clinical pathology parameters are much improved (Powles-Glover et al, 2014). This introduces the opportunity for serial sampling within the same animal for small rodent species, reducing the requirement of satellite animals merely to provide sufficient volumes to support toxicokinetic profiling (Sparrow et al, 2011;Chapman et al, 2013Chapman et al, , 2014Powles-Glover et al, 2014).…”

Utility of capillary microsampling for rat pharmacokinetic studies: Comparison of tail-vein bleed to jugular vein cannula sampling

“…Recent examples of microsampling in rodent PK or toxicokinetic (TK) studies have been published by Jonsson et al (Jonsson et al, 2012a;Jonsson, Villar, Nilsson, Eriksson, & Konigsson, 2012b;Jonsson et al, 2013;Nilsson, Ahnoff, & Jonsson, 2013), Dillen et al (Dillen et al, 2014) and Korfmacher et al (Korfmacher et al, 2015). The advantage of microsampling for rat PK studies is that the smaller volume can allow one to take more samples from each rat, so that serial bleeding could still be done even in a multiday PK study.…”