文献类型：期刊文献

英文题名：UHPLC-MS/MS Determination of Ramelteon in Rat Plasma and Its Altered Pharmacokinetics Under Simulated High Altitude: Relevance to High-Altitude Sleep Disorders

作者：Wang, Chang[1,2,3];Yan, Wen[1,2];Ma, Wenjuan[1,2];Zhang, Yingfei[2];Ji, Qian[1,2];Fang, Jingyang[2];Ma, Yuliang[2];Li, Wenbin[1,2];Wang, Rong[1,2]

第一作者：Wang, Chang

通信作者：Wang, R[1];Wang, R[2]

机构：[1]Gansu Univ Chinese Med, Coll Pharm, Lanzhou, Peoples R China;[2]Chinese Peoples Liberat Army, Hosp Joint Logist Support For 940, Dept Pharm, Lanzhou, Peoples R China;[3]Lanzhou Univ, Hosp & Clin Med Sch 2, Dept Pharm, Lanzhou, Peoples R China

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Coll Pharm, Lanzhou, Peoples R China;[2]corresponding author), Chinese Peoples Liberat Army, Hosp Joint Logist Support For 940, Dept Pharm, Lanzhou, Peoples R China.|[1073501e14fb35863569f]甘肃中医药大学药学院（西北中藏药协同创新中心办公室）;[10735]甘肃中医药大学;

年份：2026

卷号：40

期号：7

外文期刊名：BIOMEDICAL CHROMATOGRAPHY

收录：;EI(收录号：20262120758112);Scopus(收录号：2-s2.0-105039436299);WOS:【SCI-EXPANDED(收录号:WOS:001796616200003)】；

基金：This study was supported by the Innovation Fund Project for College Teachers of Gansu Provincial Department of Education (2025B-024), the Gansu Provincial Major Project (23ZDFA013-5), and the Internal Research Project of the 940th Hospital, Joint Logistics Support Force (2023YXKY001).

语种：英文

外文关键词：high-altitude sleep disorders; LC-MS/MS; pharmacokinetics; ramelteon

摘要：High-altitude hypoxia alters drug-metabolizing enzymes, potentially affecting the pharmacokinetics of sedative-hypnotics. Ramelteon, a melatonin receptor agonist for insomnia, is primarily eliminated via CYP1A2-mediated first-pass metabolism. A sensitive, ICH M10-compliant UHPLC-MS/MS method was developed for ramelteon quantification in rat plasma using only 50 mu L of sample and a 3.0-min gradient elution on a CORTECS T3 column. The method was linear over 0.5-250.0 mu g/L (LLOQ 0.5 mu g/L, R-2 > 0.995). Intraday and interday accuracy and precision were within +/- 15%, and matrix effects were consistent (IS-normalized factor 89.5-95.7%, CV <= 7.8%). The method was applied to rats exposed to simulated high altitude (6500 m, 72 h). Compared with the local altitude group (1500 m), high-altitude exposure significantly increased AUC(0-infinity) (from 247.9 to 555.8 mu g & centerdot; h/L) and C-max (from 214.0 to 693.2 mu g/L), while oral clearance (CL/F) was reduced by more than half (from 21.6 to 9.5 L/h/kg). The terminal half-life remained unchanged. Together with a proportional decrease in volume of distribution, these findings suggest that reduced first-pass metabolism and altered distribution collectively lead to an unchanged half-life. The elevated exposure indicates that a dose reduction may be warranted when ramelteon is used for high-altitude sleep disorders.