title: Utilization of dried blood spots within drug discovery: modification of a standard DiLab(®) AccuSampler(®) to facilitate automatic dried blood spot sampling.
abstract: The use of dried blood spots (DBS) in preclinical studies has seen an enormous increase over the past two years. Despite its positive impact on the 3Rs (reduce, replace and refine), its uptake in exploratory drug discovery has been limited due mainly to protracted method development time in bioanalysis but also the need for small volumes (<20 μL) to be sampled manually. Automatic blood sampling technology such as the DiLab(®) AccuSampler(®) is widely used in drug discovery to facilitate exploratory rodent-based pharmacokinetic and pharmacokinetic/pharmacodynamic studies with minimal animal handling. Propranolol was orally administered to a Han-Wistar rat attached to either a standard DiLab(®) AccuSampler(®) or a retrofitted unit designed to directly collect the DBS samples. In all, 50 or 20 μL blood samples were then collected via the standard or retrofitted unit, respectively, at six timepoints over a 7 h period. After drying and storage the DBS samples were analysed for propranolol via liquid chromatography-mass spectrometry. In this report we demonstrate that a standard DiLab(®) AccuSampler(®) can be easily retrofitted to facilitate automatic dried blood spot sampling and that time-concentration data generated from these samples are equivalent to that from manually spotted samples.
authors.affiliation: Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research and Development, Sandwich, Kent CT13 9NJ, UK. Graeme.Clark@pfizer.com
authors.forename: G T
authors.initials: GT
authors.lastname: Clark
authors.forename: G
authors.initials: G
authors.lastname: Giddens
authors.forename: L
authors.initials: L
authors.lastname: Burrows
authors.forename: C
authors.initials: C
authors.lastname: Strand
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods*; D001800:Blood Specimen Collection / Q000295:instrumentation / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D003890:Desiccation; D055808:Drug Discovery / Q000379:methods*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D011433:Propranolol / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D011433:Propranolol