{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T07:39:37Z","timestamp":1778830777819,"version":"3.51.4"},"reference-count":15,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100014103","name":"Key Technology Research and Development Program of Shandong","doi-asserted-by":"publisher","award":["2019GSF111045"],"award-info":[{"award-number":["2019GSF111045"]}],"id":[{"id":"10.13039\/100014103","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020206","name":"Health Commission of Shandong Province","doi-asserted-by":"publisher","award":["2018WS043"],"award-info":[{"award-number":["2018WS043"]}],"id":[{"id":"10.13039\/501100020206","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>LC\u20102, is a molecule of proteolysis targeting chimeras (PROTACs), with a large molecular weight, poor water solubility and low system bioavailability, which was designed to degrade KRAS<jats:sup>G12C<\/jats:sup> protein. In this study, LC\u20102 PEGylated liposomes were developed and characterized. Moreover, a rapid and sensitive liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) method in rat plasma was established and effectively utilized for an <jats:italic>in vivo<\/jats:italic> pharmacokinetic investigation. LC\u20102 PEGylated liposomes with better properties were prepared by an improved ethanol injection method. The chromatographic separation was achieved on an Agilent Eclipse XDB\u2010CN column (100\u2009\u00d7\u20092.1\u00a0mm, 3.5\u00a0\u03bcm) with acetonitrile\u2013ammonium deionized water (5\u00a0m<jats:sc>m<\/jats:sc>; 80:20, v\/v) at a flow rate of 0.5\u00a0ml\/min. The mass spectra of LC\u20102 and the IS (gefitinib) were obtained at <jats:italic>m<\/jats:italic>\/<jats:italic>z<\/jats:italic> 1132.5\u2009\u2192\u2009626.4 and 447.1\u2009\u2192\u2009128.2, respectively. The pharmacokinetic study was carried out by analyzing plasma concentrations of LC\u20102 solution or produced LC\u20102 PEGylated liposomes in rats using the developed and validated method. The pharmacokinetic results indicate that PEGylated liposome\u2010encapsulation protected LC\u20102 from the influence of endogenous protein binding, improved insolubility, prolonged half\u2010life and increased system bioavailability. This study provides a feasible solution for future preclinical and clinical studies of LC\u20102 and\/or other PROTACs.<\/jats:p>","DOI":"10.1002\/bmc.5629","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T01:20:30Z","timestamp":1679448030000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Establishment and validation of a sensitive LC\u2013MS\/MS method for the quantification of KRAS<sup>G12C<\/sup> protein PROTAC molecule LC\u20102 in rat plasma and its application to <i>in vivo<\/i> pharmacokinetic studies of LC\u20102 PEGylated liposomes"],"prefix":"10.1002","volume":"37","author":[{"given":"Yu","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong Yantai University  Yantai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Yantai Center for Disease Control and Prevention  Yantai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong Yantai University  Yantai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong Yantai University  Yantai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueqi","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong Yantai University  Yantai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yantai Center for Disease Control and Prevention  Yantai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5666-9422","authenticated-orcid":false,"given":"Sha","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong Yantai University  Yantai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.0c00411"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2017.09.010"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.11.032"},{"key":"e_1_2_7_5_1","unstructured":"European Medicines Agency. 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