{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:10:18Z","timestamp":1788952218829,"version":"build-2803163510"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    ETN101 is a new therapeutic candidate with anti-hepatocellular carcinoma activity. In the present study, three complementary liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) methods using protein precipitation and matrix-matched calibration were developed for quantifying ETN101 and its metabolites M1 and M2 in rat plasma, tissue homogenates, urine, and feces. The methods were validated with reference to U.S. Food and Drug Administration (FDA) and International Council for Harmonisation (ICH) M10 guidance. A simultaneous assay was used for plasma, urine, and feces, and two LC\u2013MS\/MS systems were used for tissue homogenates. Calibration ranges in plasma were 2\u20132,000 ng\/mL for ETN101 and 0.2\u20132,000\u00a0ng\/mL for M1 and M2. The corresponding ranges were 50\u20135,000 and 5\u2013500\u00a0ng\/mL in tissue homogenates and 20\u20132,000 and 2\u20132,000 ng\/mL in urine and feces. Across the evaluated matrices, intra- and inter-day accuracy was 87.4%\u2013115.7%, precision was \u226415.0%, and extraction recovery was 56.8%\u2013104.8%. Absolute matrix effects varied among matrices but were reproducible across six individual lots (coefficient of variation \u226415%), and stability met the prespecified criteria. The methods were applied to absorption, distribution, metabolism, and excretion (ADME) studies in rats. After once-daily oral administration at 20\u00a0mg\/kg for 5 days, ETN101 was slowly absorbed, and M1 and M2 were present in plasma and declined in parallel with the parent drug. No statistically significant fasted\u2013fed differences in 0\u201324\u00a0h systemic exposure were detected on Day 1 or Day 5, and systemic exposure to M2 exceeded that to M1. ETN101 and M2 were quantifiable in all examined tissues (liver, lung, kidney, brain, heart, spleen, testis, thyroid, stomach, small intestine, large intestine, fat, and muscle), whereas M1 was frequently below the limit of quantification in the brain and fat. The highest ETN101 tissue-to-plasma concentration ratios (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>p<\/jats:italic>\n                    <\/jats:sub>\n                    ) occurred in the lung and kidney. After intravenous administration at 10\u00a0mg\/kg, urinary recovery of each analyte was \u22640.03%, and fecal recoveries of ETN101, M1, and M2 were 0.25%, 0.76%, and 2.21%, respectively, giving a low combined recovery (approximately 3.3% of the administered dose). These methods can be selected according to the study purpose and are applicable to further preclinical pharmacokinetic and ADME studies of ETN101.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1858527","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:16:12Z","timestamp":1788948972000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Determination of ETN101, a novel anti-hepatic cancer agent and its two metabolites in rat biological matrices using LC-MS\/MS for ADME characterization"],"prefix":"10.3389","volume":"17","author":[{"given":"Woohyung","family":"Jung","sequence":"first","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University","place":["Gyeongsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunbee","family":"Jang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University","place":["Gyeongsan, Republic of Korea"]},{"name":"R&D Center, Etnova Therapeutics Corp.","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeoun-Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"R&D Center, Etnova Therapeutics Corp.","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woojin","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University","place":["Gyeongsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunbin","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University","place":["Gyeongsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaewoong","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University","place":["Gyeongsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongwon","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University","place":["Gyeongsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hun","family":"Yoon","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University","place":["Gyeongsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beom Soo","family":"Shin","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyoung","family":"Shin","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chung-Ang University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Yeungnam University","place":["Gyeongsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University","place":["Gyeongsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"B1","article-title":"Hepatocellular carcinoma","volume-title":"StatPearls","author":"Asafo-Agyei","year":"2020"},{"key":"B2","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/bjc.1998.122","article-title":"2-(4-Aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity","volume":"77","author":"Bradshaw","year":"1998","journal-title":"Br. 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