Zhang Qian, Tomazela Daniela, Vasicek Lisa A, Spellman Daniel S, Beaumont Maribel, Shyong BaoJen, Kenny Jacqueline, Fauty Scott, Fillgrove Kerry, Harrelson Jane, Bateman Kevin P
Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck & Co., Inc., West Point, PA 19486, USA.
Biologics Discovery, Merck & Co., Inc., Palo Alto, CA 94304, USA.
Bioanalysis. 2016 Apr;8(7):649-59. doi: 10.4155/bio-2015-0006. Epub 2016 Mar 15.
Reduce animal usage for discovery-stage PK studies for biologics programs using microsampling-based approaches and microscale LC-MS.
METHODS & RESULTS: We report the development of an automated DBS-based serial microsampling approach for studying the PK of therapeutic proteins in mice. Automated sample preparation and microflow LC-MS were used to enable assay miniaturization and improve overall assay throughput. Serial sampling of mice was possible over the full 21-day study period with the first six time points over 24 h being collected using automated DBS sample collection. Overall, this approach demonstrated comparable data to a previous study using single mice per time point liquid samples while reducing animal and compound requirements by 14-fold.
Reduction in animals and drug material is enabled by the use of automated serial DBS microsampling for mice studies in discovery-stage studies of protein therapeutics.
