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用UPLC-MS/MS法测定大鼠血浆中阿贝西利浓度

李颖 郭彩会 于泽芳 王智 杜文雨 刘子涵 董占军

中国临床药理学杂志2025,Vol.41Issue(15):2165-2169,5.
中国临床药理学杂志2025,Vol.41Issue(15):2165-2169,5.DOI:10.13699/j.cnki.1001-6821.2025.15.012

用UPLC-MS/MS法测定大鼠血浆中阿贝西利浓度

Determination of plasma abemaciclib in rats by UPLC-MS/MS

李颖 1郭彩会 2于泽芳 2王智 2杜文雨 2刘子涵 2董占军1

作者信息

  • 1. 河北省人民医院药学部,河北 石家庄 050051||河北省临床药学重点实验室,河北石家庄 050051
  • 2. 河北省人民医院药学部,河北 石家庄 050051
  • 折叠

摘要

Abstract

Objective To establish a UPLC-MS/MS method for detecting abemaciclib in rat plasma and to study the pharmacokinetic characteristics of abemaciclib in rats.Methods A simple protein precipitation procedure with acetonitrile was used in sample preparation.The chromatographic separation of the analytes was performed using Titank C18 column(2.1 mm × 100 mm,3 μm)at the flow rate of 0.5 mL·min-1 and a column temperature of 40℃.The wash solvents consisted of acetonitrile-methanol(1∶1;v∶v)containing 0.1%formic acid and water containing 0.1%formic acid.The analytes were ionized using positive electrospray ionization and detected using multiple reaction monitoring.The m/z transitions ions for quantification were 507.4→393.1 for abemaciclib and 515.5→393.1 for D8-abemaciclib.The validation of the method was performed regarding selectivity,calibration curve,lower limit of quantification,accuracy,precision,matrix effect,recovery,stability,and carryover.Then this method was used to determine the plasma concentration of abemaciclib in rats.Results The specificity of the established method was good.The linearity of abemaciclib in rat plasma was good within the range of 10-800 ng·mL-1,the lower limit of quantification was 10 ng·mL-1.The accuracy of both intra-day and inter-day studies were in the range of-0.03%-13.33%,and the relative standard deviation was less than 9%.The matrix factors of abemaciclib and D8-abemaciclib were between 1.01 and 1.06,and the internal standard normalized matrix effect for the low-,and high-quality control samples was 0.99 and 1.06,respectively,with RSD<8.0%,and the extraction recovery was 93.87%-111.76%.The stability and carry over were good.The main pharmacokinetic parameters of abemaciclib at 15 mg·kg-1were:AUC0-t was(9 537.80±2 716.32)μg·h·L-1,Cmax was(552.13±131.95)μg·L-1,tmax was(6.1±2.2)h,and t1/2 was(7.81±1.73)h,respectively.Conclusion This method has good sensitivity and specificity,and is simple.It is successfully applied to the pharmacokinetic study of abemaciclib in rats after oral administration,which can provide a reference for further drug interaction studies of abemaciclib.

关键词

阿贝西利/超高效液相色谱-串联质谱法/血药浓度/药代动力学

Key words

abemaciclib/ultra performance liquid chromatography-tandem mass spectrometry/plasma concentration/pharmacokientics

分类

医药卫生

引用本文复制引用

李颖,郭彩会,于泽芳,王智,杜文雨,刘子涵,董占军..用UPLC-MS/MS法测定大鼠血浆中阿贝西利浓度[J].中国临床药理学杂志,2025,41(15):2165-2169,5.

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