title: Automated DBS microsampling, microscale automation and microflow LC-MS for therapeutic protein PK.
abstract: OBJECTIVE
  Reduce animal usage for discovery-stage PK studies for biologics programs using microsampling-based approaches and microscale LC-MS.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck & Co., Inc., West Point, PA 19486, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Biologics Discovery, Merck & Co., Inc., Palo Alto, CA 94304, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Tomazela
authors.affiliation: Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck & Co., Inc., West Point, PA 19486, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Vasicek
authors.affiliation: Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck & Co., Inc., West Point, PA 19486, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Spellman
authors.affiliation: Biologics Discovery, Merck & Co., Inc., Palo Alto, CA 94304, USA.
authors.forename: Maribel
authors.initials: M
authors.lastname: Beaumont
authors.affiliation: Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck & Co., Inc., West Point, PA 19486, USA.
authors.forename: BaoJen
authors.initials: B
authors.lastname: Shyong
authors.affiliation: Safety Assessment & Laboratory Animal Resources, Merck & Co., Inc., West Point, PA 19486, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Kenny
authors.affiliation: Safety Assessment & Laboratory Animal Resources, Merck & Co., Inc., West Point, PA 19486, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Fauty
authors.affiliation: Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck & Co., Inc., West Point, PA 19486, USA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Fillgrove
authors.affiliation: Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck & Co., Inc., West Point, PA 19486, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Harrelson
authors.affiliation: Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck & Co., Inc., West Point, PA 19486, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Bateman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000493:pharmacokinetics; D001331:Automation; D001800:Blood Specimen Collection; D002851:Chromatography, High Pressure Liquid; D059788:Dried Blood Spot Testing; D006207:Half-Life; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008904:Miniaturization; D008969:Molecular Sequence Data; D011506:Proteins / Q000032:analysis* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry
chemical_list: D000911:Antibodies, Monoclonal; D011506:Proteins
keywords: DBS; LC; MS; PD; PK; automation; microflow; microsampling; sample preparation; therapeutic protein