{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T20:35:47Z","timestamp":1775680547847,"version":"3.50.1"},"reference-count":0,"publisher":"Frontiers Media SA","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Pharm Pharm Sci"],"abstract":"<jats:p>Purpose: Current practices applied to mouse pharmacokinetic (PK) studies often use large numbers of animals with sporadic or composite sampling that inadequately describe PK profiles.\u00a0 The purpose of this work was to evaluate and optimize blood microsampling techniques coupled with dried blood spot (DBS) and LC-MS\/MS analysis to generate reliable PK data in mice.\u00a0 In addition, the feasibility of cross-over designs was assessed and recommendations are presented. Methods: The work describes a comprehensive evaluation of five blood microsampling techniques (tail clip, tail vein with needle hub, submandibular, retro-orbital, and saphenous bleeding) in CD-1 mice.\u00a0 The feasibility of blood sampling was evaluated based on animal observations, ease of bleeding, and ability to collect serial samples.\u00a0 Methotrexate, gemfibrozil and glipizide were used as test compounds and were dosed either orally or intravenously, followed by DBS collection and LC-MS\/MS analysis to compare PK with various bleeding methods. Results: Submandibular and retro-orbital methods that required non-serial blood collections did not allow for inter-animal variability assessments and resulted in poorly described absorption and distribution kinetics.\u00a0 The submandibular and tail vein with needle-hub methods were the least favorable from a technical feasibility perspective.\u00a0 Serial bleeding was possible with cannulated animals or saphenous bleeding in non-cannulated animals. Conclusions:\u00a0 Of the methods that allowed serial sampling, the saphenous method when executed as described in this report, was most practical, reproducible and provided for assessment of inter-animal variability.\u00a0 It enabled the collection of complete exposure profiles from a single mouse and the conduct of an intravenous\/oral cross-over study design. \u00a0This methodology can be used routinely, it promotes the 3Rs principles by achieving reductions in the number of animals used, decreased restraints and animal stress, and improved the quality of data obtained in mouse PK studies.\u00a0This article is open to POST-PUBLICATION REVIEW. Registered readers (see \u201cFor Readers\u201d) may comment by clicking on ABSTRACT on the issue\u2019s contents page<\/jats:p>","DOI":"10.18433\/j3nk60","type":"journal-article","created":{"date-parts":[[2016,12,6]],"date-time":"2016-12-06T20:38:23Z","timestamp":1481056703000},"page":"496","source":"Crossref","is-referenced-by-count":12,"title":["Evaluation and Optimization of Blood Micro-Sampling Methods: Serial Sampling in a Cross-Over Design from an Individual Mouse"],"prefix":"10.3389","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5635-0294","authenticated-orcid":false,"given":"Nita J","family":"Patel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enaksha","family":"Wickremsinhe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Hua","family":"Hui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandar","family":"Barr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Masterson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Ruterbories","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Weller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Hanes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Kern","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Everett","family":"Perkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2016,12,6]]},"container-title":["Journal of Pharmacy &amp; Pharmaceutical Sciences"],"original-title":[],"deposited":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T13:35:13Z","timestamp":1673616913000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.library.ualberta.ca\/jpps\/index.php\/JPPS\/article\/view\/28269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,6]]},"references-count":0,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2016,11,2]]}},"URL":"https:\/\/doi.org\/10.18433\/j3nk60","relation":{},"ISSN":["1482-1826","1482-1826"],"issn-type":[{"value":"1482-1826","type":"electronic"},{"value":"1482-1826","type":"print"}],"subject":[],"published":{"date-parts":[[2016,12,6]]}}}