Methodology
A device for dried blood microsampling in quantitative bioanalysis: overcoming the issues associated with blood hematocrit
Aims: A cross-laboratory experiment has been performed on a novel dried blood sampler in order to investigate whether it overcomes issues associated with blood volume and hematocrit (HCT) that are observed when taking a subpunch from dried blood spot samples. Materials & Methods: An average blood volume of 10.6 μl was absorbed by the samplers across the different HCTs investigated (20–65%). Results:No notable change of volume absorbed was noted across the HCT range. Furthermore, the variation in blood sample volumes across six different laboratories was within acceptable limits. Conclusion: The novel volumetric absorptive microsampling device has the potential to deliver the advantages of dried blood spot sampling while overcoming some of the issues associated with the technology.
The use of dried blood spot (DBS) sampling for the collection of samples for the determina- tion of drug concentrations has received a lot of attention recently within the pharmaceutical industry [1,2]. This approach has been widely used for the determination and discovery ani- mal pharmacokinetic (PK), preclinical toxi- cokinetic, clinical PK and human therapeutic drug monitoring data [3–11]. The interest in the technique has been driven by its advantages over conventional plasma sampling for these study designs. These advantages include;
• Reduced blood volumes (<20 μl com- pared with >200 μl), leading to ethical benefits in rodent PK and toxicokinetic studies (reductions in the numbers of animals used and refinements in the warming procedures required to encour- age blood flow) and its applicability to pediatric study designs;
• Simplified sample collection workflows, obviating the requirements for centrifu- gation, plasma transfer and frozen sample storage and transfer;
• Increased or suitable stability for some analytes without requiring frozen storage [12–16];
10.4155/BIO.14.310 © Phenomenex LTD
• Ability to obtain high-quality samples in locations not previously readily amenable for collection (e.g., patient homes and remote locations);
• Cost savings associated with the shipping and storage of study samples at ambi- ent room temperature rather than frozen, and a requirement for reduced amounts of experimental drug substances, particularly for discovery studies.
However, recent publications have high-
lighted a number of issues that have the potential to adversely affect the quality of the quantitative data obtained from DBS samples when a subpunch is taken from a sample [17–21]. Most practitioners prefer to use the subpunch method for DBS sam- pling as it simplifies the initial collection and spotting of the sample by removing the need to use accurate volume spotting techniques. Instead, the animal technician or clinician can spot an approximate vol- ume from which a fixed-diameter subpunch can be taken in order to realize an accurate volume at the point of analysis. However, this approach relies on the blood spreading evenly when initially spotted. Recent stud- ies have clearly demonstrated that the blood
Bioanalysis (2015) 7(6), 653–659
Neil Spooner*,1 Denniff1
Woods4 Xu5
Zane7 , Philip
Ronald De Vries2 Ji3
, Luc Michielsen2 , Qin C
, Mark E Arnold3 , Valérie Boutet6
James B Rudge9 1
, Eric J Woolf5 , Stuart Kushon8 , , Karen , Yang
, Patricia &
Bioanalytical Science & Toxicokinetics,
Drug Metabolism & Pharmacokinetics, GlaxoSmithKline Research &
Development, Ware, UK 2
Bioanalysis Department, Janssen
Research & Development, Turnhoutseweg 30, 2340 Beerse,
Belgium 3
Bioanalytical Science & Selective Integration, Bristol-Myers Squibb, Co.,
Princeton, NJ 08543, USA 4
Pre Clinical Bioanalysis & Toxicokinetics
AstraZeneca, Alderley Park, UK 5
Point, PA 19486, USA 6
Merck Research Laboratories, PPDM- Global Bioanalytics, WP 75B-300, West
Sanofi Recherche & Developpement, 3 digue d’Alfortville, Bâtiment Claude
Bernard, 94140, Alfortville, France 7
NJ 08807, USA 8
Sanofi, 55 Corporate Drive, Bridgewater, Neoteryx, LLC, 421 Amapola Avenue,
Torrance, CA 90501, USA 9
Phenomenex, 411 Madrid Avenue,
Torrance, CA 90501, USA *Author for correspondence: Tel.: +44 1920 882550 Fax: +44 1920 884140
neil.spooner@gsk.com
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ISSN 1757-6180
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