In recent years there has been renewed interest in the Dried Blood Spot technique for determining drug levels in blood samples. The advantages it offers – including less blood per sample, easier logistics due to longer shelf life, non-hazardous samples, storage at ambient temperature, and reduced costs – are helping Dried Blood Spot gain momentum as a popular alternative to the traditional plasma/serum blood sampling technique.
Although Dried Blood Spot has been in existence for almost 50 years, it had not been widely utilized within the drug discovery and development process due to limitations of the method. In the past, analytical technologies were not sensitive enough to obtain reliable, quantitative data from such tiny blood samples. However, recent advancements – mainly ultra-high performance liquid chromatography and mass spectrometry (LC-MS/MS) – have overcome this limitation, enabling Dried Blood Spot to not only screen for the presence or absence of a particular molecule, but also to quantitatively determine the extent to which a molecule is present.Here’s how the Dried Blood Spot method works: a small amount of animal or human blood is spotted onto a collection card that is then air dried, stored, and shipped at room temperature to the desired bioanalytical location for analysis. For compound concentration analysis, the blood spot is punched out of the Dried Blood Spot card and analyzed following a validated LC-MS/MS bioanalytical method.
Overall, Dried Blood Spot is an innovative technique that reduces sample volume requirements while offering significant economical and ethical benefits, including alignment with ‘the 3R’s’ principles (replacement, reduction, and refinement of animal testing). As drug developers continue to discover these new advantages, the use of Dried Blood Spot is booming in both nonclinical and clinical studies.
The use of Dried Blood Spot in nonclinical studies can result in up to an 85 percent reduction in the volume of blood collected at each time point, which has a significant impact on animal studies and data quality. In rodent studies, the number of animals needed can be reduced by up to 50%, and because fewer animals are needed, the quantity of compound needed for testing is also greatly reduced. Serial sampling of individual rodents can also be used instead of composite sampling, resulting in a higher quality of toxicological (TK) data. This less invasive sampling procedure also greatly reduces animal stress.
As for clinical studies, one major benefit offered by Dried Blood Spot is ease of sampling. The simplified, less invasive finger prick is much more patient friendly than blood draws and the most often preferred method by volunteers and clinical staff. This small sample volume also makes Dried Blood Spot ideal for pediatric studies.
Furthermore, since Dried Blood Spot can be stored at room temperature, refrigeration is not needed for storage or shipping, which greatly reduces costs. The reduced amount of specialized equipment also makes Dried Blood Spot technology extremely valuable when conducting clinical studies in emerging countries where centrifuges and freezers are not readily available.
Finally, chemically coated Dried Blood Spot cards are less hazardous than plasma tubes, as they offer bacterial lysis and inactivate HIV and Hep B. This results in easier transportation because Dried Blood Spot samples can be shipped as non-hazardous materials using regular mail or courier services.
Dried Blood Spot at Covance
Launched in July 2009, Covance was the first CRO to globally support Dried Blood Spot with integrated GLP toxicology and bioanalytical services. Currently, Covance is defining its clinical Dried Blood Spot offering and driving to be the first CRO to globally offer integrated Dried Blood Spot support across toxicology, clinical pharmacology, and bioanalytical.
With benefits throughout the entire drug development process, Dried Blood Spot has become a hot topic in the industry. Therefore, Covance is doing its part by sharing information on Dried Blood Spot from our scientists, as well as relevant information we’re finding through our partners, scientists, and online community. For up-to-date information and analysis from Covance on the Dried Blood Spot technique, visit http://www.covance.com/products/nonclinical/bioanalytical/dried-blood-spots.php
About the Author
Lee Goodwin, Ph.D., is Head of Bioanalysis at Covance, Harrogate. Lee received his B.Sc. and Ph.D. from the University of York and has more than 10 years experience in small molecule bioanalysis by LC-MS/MS including four years at Covance. He has 13 peer reviewed publications including several on Dried Blood Spot and is on the Editorial Board of Journal of Chromatographic Science.