Utilization of DBS Within Drug Discovery: Development of a Serial Microsampling Pharmacokinetic Study in Mice

Clark, Graeme T; Haynes, Julian J; Bayliss, Mark; Burrows, Lisa

doi:10.4155/bio.10.91

Cited by 57 publications

(37 citation statements)

References 14 publications

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“…Clark et al [17]. showed that FTA Elute papers produced the most marked matrix effects and therefore comparisons were made using S&S 903 filter paper.…”

Section: Matrix Effectmentioning

confidence: 99%

Dried Blood Spot Sampling with LC-MS Analysis for Routine Therapeutic Caffeine Monitoring in Neonates

Lawson

Patel

Mulla

et al. 2012

ISRN Chromatography

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A liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for the determination of therapeutic levels of caffeine in dried blood spot (DBS) samples. Caffeine is used in the treatment of Apnoea of Prematurity (AoP) in newborn children. Calibration DBS samples were prepared by spotting 15 µL of whole blood spiked with the analyte onto specimen collection cards. 3 mm disks cut from the centre of the DBS were extracted in methanol containing the internal standard. The extract was separated using a Zorbax Eclipse Plus C18 column and the MS, operated in electrospray positive ion mode, used single ion monitoring at m/z 195 for caffeine and m/z 198 for the IS. The overall extraction recovery of caffeine from spiked blood spots was demonstrated to be 44-47%. Validation of the microanalytical method showed good precision (coefficient of variation) and accuracy (relative error) and specificity and was linear within the tested calibration range 500-25000 ng/mL for caffeine. Investigation of different specimen collection papers revealed different matrix effects with significant ion suppression from the FTA Elute paper itself. Requiring only a microvolume (15 µL) blood sample for analysis, the developed DBS based microanalytical method has the potential to facilitate the routine monitoring of caffeine in neonates.

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“…Clark et al [17]. showed that FTA Elute papers produced the most marked matrix effects and therefore comparisons were made using S&S 903 filter paper.…”

Section: Matrix Effectmentioning

confidence: 99%

Dried Blood Spot Sampling with LC-MS Analysis for Routine Therapeutic Caffeine Monitoring in Neonates

Lawson

Patel

Mulla

et al. 2012

ISRN Chromatography

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“… DBS environmental conditions during ambient shipping and storage across international borders (49) .  DBS sample homogeneity (50,51,52,21) .…”

Section: Recent Investigations Into Fundamentals Principles Associatementioning

confidence: 99%

Direct Analysis of Dried Blood Spot Samples

Abu-Rabie¹

2014

Dried Blood Spots

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“…Tail vein sampling (tail clip and tail vein with needle hub) seems to be the most commonly used micro-sampling technique in mice (2,12,30,31) while saphenous bleeds and retroorbital bleeds have also been used (3,4,12). The use of tail clips and tail vein with a hub needle should be avoided to reduce contamination of samples with administered dose, especially in small rodents such as mice when drug/test compounds are administered IV via the tail vein.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the adoption of various bleeding techniques to enable micro-sampling of blood or plasma (generally defined as the collection of blood volumes of less than 50 µL) has enabled the collection of multiple PK time points and the generation of a complete PK profile from a single mouse. These techniques include micro-sampling of plasma either as liquid plasma (8)(9)(10), or as dried plasma spots (11), and micro-sampling of blood either as liquid blood (12)(13)(14)(15), or as dried blood spots (DBS) (2)(3)(4)(16)(17)(18). Overall, micro-sampling also benefits the adoption and compliance with the 3Rs principles (Reduction, Refinement, and Replacement in animal usage) (19).…”

Section: Introductionmentioning

confidence: 99%

“…Overall, the sampling volumes and the collection techniques have undergone very little change over the past few decades. The volume of blood collected at each sampling time-point has been dictated by the volume of sample needed for the analysis, typically about 150 to 200 µL of blood from a mouse, which limits the number of sampling time-points to two or three bleeds per mouse (one or two surviving bleeds followed by a terminal bleed) (2)(3)(4)(5). Therefore, generating a complete PK or TK profile in a single mouse with conventional plasma collection methods is not possible due to the limitations in blood volumes that can be collected without impacting the animal's health and investigators resort to the generation of composite PK/TK profiles with nonserial bleeds (6).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation and Optimization of Blood Micro-Sampling Methods: Serial Sampling in a Cross-Over Design from an Individual Mouse

et al. 2016

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-Purpose: Current practices applied to mouse pharmacokinetic (PK) studies often use large numbers of animals with sporadic or composite sampling that inadequately describe PK profiles. The purpose of this work was to evaluate and optimize blood microsampling techniques coupled with dried blood spot (DBS) and LC-MS/MS analysis to generate reliable PK data in mice. In addition, the feasibility of cross-over designs was assessed and recommendations are presented. Methods: The work describes a comprehensive evaluation of five blood microsampling techniques (tail clip, tail vein with needle hub, submandibular, retro-orbital, and saphenous bleeding) in CD-1 mice. The feasibility of blood sampling was evaluated based on animal observations, ease of bleeding, and ability to collect serial samples. Methotrexate, gemfibrozil and glipizide were used as test compounds and were dosed either orally or intravenously, followed by DBS collection and LC-MS/MS analysis to compare PK with various bleeding methods. Results: Submandibular and retro-orbital methods that required non-serial blood collections did not allow for inter-animal variability assessments and resulted in poorly described absorption and distribution kinetics. The submandibular and tail vein with needle-hub methods were the least favorable from a technical feasibility perspective. Serial bleeding was possible with cannulated animals or saphenous bleeding in non-cannulated animals. Conclusions: Of the methods that allowed serial sampling, the saphenous method when executed as described in this report, was most practical, reproducible and provided for assessment of inter-animal variability. It enabled the collection of complete exposure profiles from a single mouse and the conduct of an intravenous/oral cross-over study design. This methodology can be used routinely, it promotes the 3Rs principles by achieving reductions in the number of animals used, decreased restraints and animal stress, and improved the quality of data obtained in mouse PK studies.

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Utilization of DBS Within Drug Discovery: Development of a Serial Microsampling Pharmacokinetic Study in Mice

Abstract: Serial microsampling and DBS in exploratory mouse pharmacokinetic has been shown to provide superior data quality when compared with traditional plasma-based composite studies.

Cited by 57 publications

References 14 publications

Dried Blood Spot Sampling with LC-MS Analysis for Routine Therapeutic Caffeine Monitoring in Neonates

Dried Blood Spot Sampling with LC-MS Analysis for Routine Therapeutic Caffeine Monitoring in Neonates

Direct Analysis of Dried Blood Spot Samples

Evaluation and Optimization of Blood Micro-Sampling Methods: Serial Sampling in a Cross-Over Design from an Individual Mouse

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