{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T10:49:00Z","timestamp":1784371740926,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>Radiolabeled human mass balance studies are crucial for identifying circulating metabolites and understanding drug absorption, excretion, and clearance pathways. Metabolite profiling involves quantifying all drug\u2010related entities, including parent drug and metabolites in plasma and excreta, using extended liquid chromatography methods coupled with detection through scintillation counting, accelerator mass spectrometry, or non\u2010radiolabeled approaches. Given the labor\u2010intensive nature of sample extraction and analysis, we propose a new paradigm that maximizes gathering information through sample pooling strategies. Our proposal introduces sample pooling strategies by integrating both individual and pooled sample schemes, simplifying decisions, and consolidating existing knowledge into a cohesive document. This aligns with the low statistical power typically associated with mass balance studies that dose six to eight subjects. In metabolite profiling, it is common practice to pool samples either from the limited number of subjects participating in a human mass balance study or from different time points of sample collection. This approach improves efficiency while preserving data integrity. Pooling reduces resource constraints and enables the concentration of samples with relatively low radioactivity levels, resulting in higher quality metabolite profiles. Nevertheless, there are situations when analyzing samples from individual subjects or time points may be preferred. This proposal presents guidance and decision trees designed to facilitate informed decisions about sample pooling to maximize data quality of metabolite profiling in human mass balance studies while efficiently managing resources. These recommendations stem from discussions within the mass balance working group of the IQ Consortium.<\/jats:p>","DOI":"10.1002\/cpt.70157","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T01:04:03Z","timestamp":1766019843000},"page":"591-597","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Guided Sample Pooling in Human Mass Balance Studies: A Recommended Strategic Decision Framework"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4956-1418","authenticated-orcid":false,"given":"Filip","family":"Cuyckens","sequence":"first","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6340-8286","authenticated-orcid":false,"given":"Wenying","family":"Li","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6507-237X","authenticated-orcid":false,"given":"Adam M.","family":"Auclair","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth C.","family":"Cassidy","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3083-5362","authenticated-orcid":false,"given":"Cathy","family":"Cantalloube","sequence":"additional","affiliation":[{"name":"Sanofi  Vitry sur\u2010Seine France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3717-2231","authenticated-orcid":false,"given":"Gary","family":"Collins","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8420-2456","authenticated-orcid":false,"given":"Alexander D.","family":"James","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1719-8629","authenticated-orcid":false,"given":"Chris","family":"Gibson","sequence":"additional","affiliation":[{"name":"Incyte  Wilmington Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Glaenzel","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7121-4394","authenticated-orcid":false,"given":"Felix","family":"Huth","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Kang","sequence":"additional","affiliation":[{"name":"Vertex  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6066-9977","authenticated-orcid":false,"given":"Patricia","family":"Moliner","sequence":"additional","affiliation":[{"name":"Sanofi  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2290-3934","authenticated-orcid":false,"given":"Mette L.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6745-3069","authenticated-orcid":false,"given":"Isabel","family":"Piel","sequence":"additional","affiliation":[{"name":"Bayer AG  Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5271-7773","authenticated-orcid":false,"given":"Pietro","family":"Brunetti","sequence":"additional","affiliation":[{"name":"F. Hofmann\u2010La Roche  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4497-0516","authenticated-orcid":false,"given":"Hanno","family":"Schieferstein","sequence":"additional","affiliation":[{"name":"The Healthcare Business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3649-5673","authenticated-orcid":false,"given":"David","family":"Wagner","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0129-1682","authenticated-orcid":false,"given":"Gregory S.","family":"Walker","sequence":"additional","affiliation":[{"name":"Pfizer  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3282-1343","authenticated-orcid":false,"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6326-458X","authenticated-orcid":false,"given":"Qin","family":"Yue","sequence":"additional","affiliation":[{"name":"Gilead Sciences  Foster City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5628-0028","authenticated-orcid":false,"given":"Jason","family":"Boer","sequence":"additional","affiliation":[{"name":"Incyte  Wilmington Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8385-9288","authenticated-orcid":false,"given":"Cyrus","family":"Khojasteh","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals M3 (R2)<https:\/\/database.ich.org\/sites\/default\/files\/M3\u00a0R2\u00a0Guideline.pdf> (2009)."},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12540"},{"key":"e_1_2_9_3_1","unstructured":"US Food & Drug Administration: Clinical Pharmacology Considerations for Human Radiolabeled Mass Balance Studies<https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/clinical\u2010pharmacology\u2010considerations\u2010human\u2010radiolabeled\u2010mass\u2010balance\u2010studies> (2024)."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3144"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.122.000955"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.661"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2020.1821123"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2006.09.019"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.117.079574"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.119.090324"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.117.075358"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00667-8"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.114.060061"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c01293"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.722"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.122.001006"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200645010-00003"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602532.2016.1181081"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2013.831143"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13108"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.113"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.124.001636"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.124.001751"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-019-01162-7"},{"key":"e_1_2_9_25_1","unstructured":"International Commission on Radiological Protection (ICRP) Publication 100: Human alimentary tract model for radiological protection<https:\/\/www.icrp.org\/publication.asp?id=ICRP%20Publication%20100> (2006)."},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.120.000349"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.039339"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1981.56"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/js970486q"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-019-03793-7"},{"key":"e_1_2_9_31_1","unstructured":"European Medicines Agency: Overview of comments received on \u2018Guideline on the Investigation of Drug Interactions\u2019 (EMA\/CHMP\/EWP\/125211\/2010)<https:\/\/www.ema.europa.eu\/en\/documents\/other\/overview\u2010comments\u2010received\u2010guideline\u2010investigation\u2010drug\u2010interactions_en.pdf> (2013)."},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.112.044933"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2025.2505637"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.121.000632"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1255"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-024-00930-3"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-022-04470-y"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70157","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70157","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70157","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T07:10:36Z","timestamp":1771312236000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,17]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/cpt.70157"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70157","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,17]]},"assertion":[{"value":"2025-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}