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.

Automated Direct Extraction and Analysis of Dried Blood Spots Employing On-Line SPE High-Resolution Accurate Mass Bioanalysis

“…DBS techniques have been widely used since the 1960s for neonatal screening of inherited metabolic disorders [8,9], and recently, the use of DBS has been greatly increased by the enhanced sensitivity and selectivity offered by LC-MS, an important factor for the measurement of drugs from DBS obtained from few microliters of blood [10][11][12]. As a result, numerous bio-analytical applications have demonstrated the utility of DBS in pharmacokinetic and toxicokinetic studies, therapeutic drug monitoring and drug discovery [13][14][15][16][17].…”

Application of Automated Dried Blood Spot Sampling and LC–MS/MS for Pharmacokinetic Studies of AMG 517 in Rats

“…Manual blood spotting is time consuming and labor intensive and may introduce variation in the homogeneity of the DBS samples due to human error. Automated blood collection and spotting [23] can reduce animal stress, human error and resource needs, as well as allowing for overnight sample collection. Also immediate collection of samples on DBS cards…”

Design and operation of an automated high-throughput monoclonal antibody facility

“…Some of these applications are on a significantly large scale, such as the fully automated liquid handling 'barns' that pharmaceutical companies use to manage the millions of compounds they test and synthesise every year (Cui et al 2011;Schmitt et al 2010), or the automated liquid handling with integrated testing and detection instrumentation for ultra high throughput screening of those compounds (Michael et al 2008). On the other end of the scale is the relatively low throughput but fully automated in vivo sample collection system used in pharmacokinetic and other pre-clinical studies (Clark et al 2011;Aryal et al 2012). Many laboratories use some type of automation in the form of liquid handling systems (Joelsson et al 2008) (automated sample analysis for Mass Spectrometry and HPLC and automated plate readers, for example) to facilitate their daily scientific research (Uyeda et al 2011).…”