Optimization of bioanalysis of dried blood samples

• Published in: Journal of pharmacological and toxicological methods Vol. 123; p. 107296
• Main Authors: Alizadeh, Elham Ataei, Rast, Georg, Cantow, Chris, Schiwon, Jessica, Krause, Florian, De Meyer, Guido R.Y., Guns, Pieter-Jan, Guth, Brian D., Markert, Michael
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2023
• Subjects: Bioanalysis; Dog; Drug concentration; In-vivo blood sampling; PK/PD; Safety pharmacology; PK/PD; Concentration in plasma; Dried Blood Samples; Safety pharmacology; Pharmacodynamic; Committee for Medicinal Products for Human Use; Biopharmaceutics Classification System; Pharmacokinetic; Whole Blood; Ethylenediaminetetraacetic acid; Concentration in blood; Compound Concentration; Bioanalysis; In-vivo blood sampling; Drug concentration; European Medicines Agency; Minimum Detectable Difference; Dog; Food and Drug Administration
• ISSN: 1056-8719; 1873-488X
• DOI: 10.1016/j.vascn.2023.107296

Pharmacokinetic/pharmacodynamic modelling has emerged as a valuable technique for understanding drug exposure and response relationships in drug development. Pharmacokinetic data are often obtained by taking multiple blood samples, which may disturb physiological parameters and complicate study designs. Wearable automatic blood sampling systems can improve this limitation by collecting dried blood samples at programmable time points without disrupting cardiovascular parameters. It is the objective of this study to evaluate the bioanalysis of DBS in comparison to conventional blood sampling techniques and to optimize the recovery of various compounds spiked into canine blood dried on filter paper tape. Incubated blood samples from Beagle dogs were spiked with 16 different compounds and half of the whole blood sample was centrifuged to obtain plasma. After the dried blood sample drops were dried, liquid chromatography-mass spectrometry methods were used to analyze the samples. The study explored different anticoagulants, sample preparation methods and technical approaches to best determine the compound concentrations in dried blood samples. With the two anticoagulants tested and using the optimized sample preparation methods and technical approaches we employed, the bioanalysis of dried blood samples can provide equivalent results to conventional blood sampling techniques. Automated blood sampling systems have the potential to provide increased numbers of blood samples, providing substantially more Pharmacokinetic data within safety pharmacology studies without disrupting physiological parameters. They can provide a viable alternative to traditional methods of obtaining blood for various other types of studies or analyses.