Application of the DBS Methodology to a Toxicokinetic Study in Rats and Transferability of Analysis Between Bioanalytical Laboratories

Turpin, Phillip E.; Burnett, Josephine; Goodwin, Lee; Foster, Amanda; Barfield, Matthew

doi:10.4155/bio.10.88

Cited by 32 publications

(15 citation statements)

References 18 publications

(18 reference statements)

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“…In addition, there are much reduced analyte stability concerns in the dried sample [6,7]. Supporting the reliability of the technique, there are reports of concentration data obtained from DBS correlating well with those data obtained from analysis of liquid samples [8]. As it stands, DBS has cemented itself as an option in the regulated laboratory, despite reliability-related question marks over aspects such as the impact of differing hematocrit [9] and uncertainty over best means of internal standard addition [10].…”

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confidence: 87%

Instrumental and Technical Evolution Over the Past Decade in Bioanalysis

MacNeill

2019

Bioanalysis

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In the domain of LC-MS, it has been an exciting and memorable 10 years of progress in quantitative bioanalytical techniques since the inception of Bioanalysis. Several innovative technologies have seen commercial manifestations, of wonderful value to the pharmaceutical and biotech industries. As such, we have seen drive and success in improving sensitivity of detection, a perennial pursuit. We have seen the creation of more avenues to obtain selectivity, the most pivotal property of a truly robust quantitative methodology. We have also significantly brought forward and established new ways to reliably use notably less matrix in fully quantitative applications. In this article, I have detailed my pick of the most compelling developments in the past decade. Matrix quantity basis reduction with innovationOn the note of reduction of analytical matrix volumes, the launch of this journal occurred just as a formidable wave of interest was gaining strength in dried blood spotting (DBS). There was a pronounced focus on a quantitative LC-MS end point as shown in the first of such reports [1,2] and for which there have been some informative and insightful reviews over the years [3,4]. The technique of DBS, an example of microsampling, involves minimally invasive drawings typically in the order of 10 μl, resulting in several practical and analytical advantages. The dramatic reduction in the blood volume required for a given toxicokinetic time point gives a concomitant reduction in animal number requirements, particularly important for the likes of rodents. Indeed, full toxicokinetic (TK) profiles can be acquired from a single animal, bestowing far greater confidence in concentration data and the derived statistical data and associated decisions from such. The card-based sample collection also has profound cost-saving implications, from the perspective of ease of storage and transport [5]. In addition, there are much reduced analyte stability concerns in the dried sample [6,7]. Supporting the reliability of the technique, there are reports of concentration data obtained from DBS correlating well with those data obtained from analysis of liquid samples [8]. As it stands, DBS has cemented itself as an option in the regulated laboratory, despite reliability-related question marks over aspects such as the impact of differing hematocrit [9] and uncertainty over best means of internal standard addition [10]. In any case, DBS has not just preclinical [11] but naturally also clinical application [2,12], the amount of blood required being no more than that obtained from a finger prick, and in this manner there are positive implications for the likes of pediatric studies.In the same microsampling vein, the acquisition and storage of liquid samples in this order of volume also gained great prominence on the heels of DBS, and with the same 3R (reduction, replacement and refinement) benefits for research involving animals. Liquid microsampling has overwhelmingly involved capillaries of 1-25 μl in the drawing and storage of blood samples [...

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confidence: 87%

Instrumental and Technical Evolution Over the Past Decade in Bioanalysis

MacNeill

2019

Bioanalysis

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“…These huge ethical benefits are excellent examples of the reduction and refinement aspects of the 3R principles, which link scientific excellence with humane use of laboratory animals . Reduction in the volume of blood drawn per time point enables the utilization of serial rather than composite sampling for better correlation of exposure and effect . On the other hand, the principal merits that DBS offers for clinical studies lie in its applicability for pediatric and juvenile studies and room temperature sample storage/shipping—a logistic advantage .…”

Section: Introductionmentioning

confidence: 99%

Perforated dried blood spot accurate microsampling: the concept and its applications in toxicokinetic sample collection

Ploch

Fast

et al. 2012

J. Mass. Spectrom.

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Dried blood spot (DBS) sampling has gained considerable interest as a microsampling technique to support drug discovery and development owing to its enormous ethical and practical benefits. Quantitative determinations of drugs and/or their metabolites collected in DBS matrix in its current format, however, have encountered technical challenges and regulatory uncertainty. The challenges of DBS bioanalysis are largely ascribed to the way how samples are collected and analyzed. Currently, an uncontrolled amount of a blood sample, e.g. 20 µl, is collected per time point per sample and spotted onto cellulose paper. Quantitation is based on removal of a fixed area of the DBS sample, resulting in sample waste, a need for mechanical punching and concomitant potential punching carryover, uncertainty in recovery assessment and the adverse impact of hematocrit on accurate quantitation. Here, we describe the concept and applications of a novel concept, namely perforated dried blood spot (PDBS), for accurate microsampling that addresses previous challenges. Advantages of PDBS are enumerated and compared with conventional DBS in the context of microsampling and liquid chromatography tandem mass spectrometry bioanalysis. Two approaches for accurate microsampling of a small volume of blood (5 µl) are proposed and demonstrated, i.e. Microsafe® pipettes and the Drummond incremental pipette. Two online sample enrichment techniques to enhance liquid chromatography tandem mass spectrometry sensitivity for microsampling bioanalysis are discussed. The PDBS concept was successfully applied for accurate sample collection (5 µl) in a toxicokinetic study in rats given a single oral gavage dose of acetaminophen. Perspectives on bioanalytical method validation for regulated DBS/PDBS microsampling are also presented.

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“…These constraints are greatly relieved by 'microsampling', resulting in the generation of DBS and allowing serial sampling from a strongly reduced amount of laboratory animals, including small rodents such as mice. This allows the replacement of composite pharmaco-or toxicokinetic profiles (obtained from different animals) by serial profiles (obtained within individual animals), which leads to higher data quality ( Clark et al, 2010, Turpin et al, 2010, Crawford et al, 2011. Apart from a large improvement in animal welfare, DBS sampling is also beneficial for the (pharmaceutical) companies involved.…”

Section: Analysis Of Therapeutic Drugs -Toxicokineticsmentioning

confidence: 99%

Dried blood spots in toxicology: from the cradle to the grave?

Stove

Ingels

Kesel

et al. 2012

Critical Reviews in Toxicology

145

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About a century after its first described application by Ivar Bang, the potential of sampling via dried blood spots (DBS) as an alternative for classical venous blood sampling is increasingly recognized. Perhaps best known is the use of DBS in newborn screening programs, ignited by the hallmark paper by Guthrie and Susi half a century ago. However, it is only recently that both academia and industry have recognized the many advantages that DBS sampling may offer for bioanalytical purposes, as reflected by the strong increase in published reports during the last few years. Currently, major DBS applications include newborn screening for metabolic disorders, epidemiological surveys (e.g. HIV monitoring), therapeutic drug monitoring (TDM), as well as toxicology. In this review, we provide a comprehensive overview of the distinct subdisciplines of toxicology for which DBS sampling has been applied. DBS sampling for toxicological evaluation has been performed from birth until autopsy, aiming at the assessment of therapeutic drugs, drugs of abuse, environmental contaminants, toxins, as well as (trace) elements, with applications situated in fields as toxicokinetics, epidemiology and environmental and forensic toxicology. We discuss the strengths and limitations of DBS in the different subdisciplines and provide future prospects for the use of this promising sampling technique in toxicology.

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Application of the DBS Methodology to a Toxicokinetic Study in Rats and Transferability of Analysis Between Bioanalytical Laboratories

Cited by 32 publications

References 18 publications

Instrumental and Technical Evolution Over the Past Decade in Bioanalysis

Instrumental and Technical Evolution Over the Past Decade in Bioanalysis

Perforated dried blood spot accurate microsampling: the concept and its applications in toxicokinetic sample collection

Dried blood spots in toxicology: from the cradle to the grave?

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