Validation and clinical application of dried blood spot assay for quantitative assessment of edoxaban in healthy adults

• Published in: Bioanalysis Vol. 12; no. 6; pp. 393 - 407
• Main Authors: He, Ling, Gajee, Roohi, Mangaraj, Raj, Waldron, Michael P, Brown, Karen S
• Format: Journal Article
• Language: English
• Published: England Newlands Press Ltd 01.03.2020; Informa UK Limited; Newlands Press
• Subjects: Acids; Anticoagulants; bioanalytical method validation; Blood; Chromatography; Clinical medicine; concordance; Cross-Over Studies; dried blood spot; Dried Blood Spot Testing; Dried Blood Spot Testing - methods; edoxaban; Factor Xa Inhibitors; Factor Xa Inhibitors - pharmacology; Factor Xa Inhibitors - therapeutic use; finger prick; Healthy Volunteers; Hematocrit; Humans; incurred sample analysis; Ions; Medical screening; Metabolites; Pharmacokinetics; Plasma; Pyridines; Pyridines - pharmacology; Pyridines - therapeutic use; Quantitation; Reproducibility of Results; Sampling; Thiazoles; Thiazoles - pharmacology; Thiazoles - therapeutic use; United States > US; bioanalytical method validation; finger prick; dried blood spot; edoxaban; concordance; incurred sample analysis
• ISSN: 1757-6180; 1757-6199
• DOI: 10.4155/bio-2019-0180

Dried blood spot (DBS) is a sampling approach that offers several advantages over plasma and whole blood (WB) sampling, but several factors, such as hematocrit and temperature, can adversely affect quantitation. In an open-label, three-way crossover study in healthy subjects, we explored the correlation between DBS, WB and plasma samples, and between DBS samples from finger-prick and venipuncture blood for measuring edoxaban and its metabolite M-4 using LC–MS/MS. The methods were validated comprehensively. The incurred sample reanalysis experiments demonstrated quantitation reproducibility in all three matrices. Overall, there was a good correlation (near perfect concordance for edoxaban) among plasma, WB and DBS measurements. M-4 concentrations in DBS and WB were lower than in plasma. These results indicate using DBS may be used as an alternative methodology to measure edoxaban pharmacokinetics.