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To investigate the pharmacokinetic\u2013pharmacodynamics behavior of lenvatinib and its active metabolites in advanced HCC patients, it is important to develop a simple and rapid method to analyze the exposures of lenvatinib and its metabolites in human samples. Here, we established and validated a simple and rapid method for determining lenvatinib and its three major metabolites, descyclopropyl lenvatinib (M1), O\u2010demethyl lenvatinib hydrochloride (M2), and lenvatinib N\u2010Oxide (M3) by liquid chromatography\u2010tandem mass spectrometry method. Lenvatinib and its main metabolites were separated on an X\u2010Terra RP18 column (50 \u00d7 2.1\u00a0mm, 3.5 \u00b5m) at 35\u00b0C within 3\u00a0min, and the analytes were isocratically eluted with the mobile phase of methanol\u2013water (10:90, v\/v) containing 0.1% of formic acid at a flow rate of 0.15\u00a0mL\/min. The calibration range was 1\u20131000\u00a0ng\/mL for lenvatinib, while 0.1\u2013100\u00a0ng\/mL for M1\u2013M3 under positive electrospray ionization mode. The inter\u2010 and intra\u2010batch precisions and accuracy were acceptable for lenvatinib and its metabolites. This method was successfully applied to measure lenvatinib and its metabolites in plasma samples from HCC patients, which provides a robust tool for pharmacokinetic\u2013pharmacodynamics studies of lenvatinib.<\/jats:p>","DOI":"10.1002\/jssc.70042","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:14:58Z","timestamp":1733184898000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Development and Validation of a Sensitive LC\u2013MS\/MS Method for Determination of Lenvatinib and Its Major Metabolites in Human Plasma and Its Application in Hepatocellular Carcinoma Patients"],"prefix":"10.1002","volume":"47","author":[{"given":"Shaoxing","family":"Guan","sequence":"first","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guosheng","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis Research Department of Infectious Diseases Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofang","family":"Bi","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Yu","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Hong","family":"Fang","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhang","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis Research Department of Infectious Diseases Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5136-0388","authenticated-orcid":false,"given":"Huichang","family":"Bi","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30207-1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00392"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2019.12.001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.917"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-020-04178-x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.14740\/wjon1399"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2012.01.004"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-017-0403-4"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.114.058073"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112391"},{"key":"e_1_2_10_12_1","unstructured":"US. 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