中国药理学通报Issue(4)：570-575,6.DOI:10.3969/j.issn.1001-1978.2015.04.026
LC-MS／MS法测定Beagle犬血浆中布洛芬对映体的浓度
Vailidation of a LC-MS/MS method for quantification of ibuprofen enantiomers in Beagle dog plasma
摘要
Abstract
Aim To develop a simple,rapid and ac-curate analysis method for determination of chiral ibu-profen in Beagle dog plasma.Method The plasma sample was submitted to liquid - liquid extraction u-sing hexane /isopropanol (95 ∶5,V/V),with ketopro-fen as the internal standard (IS).The separation was accomplished in a Lux 5u Cellulose-3 (250 mm·4.6 mm,5 μm)column,and the mobile phase consisted of methanol and a mixture of 1 mmol·L -1 ammonium acetate-methanol-formic acid (90 ∶1 0 ∶0.2,V/V/V) with the volume ratio of 82 ∶1 8 at a flow rate of 0.8 mL· min -1 .The mass spectrometer consisted of an ESI interface operating at negative ionization mode and the detection was performed using multiple reaction monitoring at the transitions of m /z 205.2 /1 61 .2 for ibuprofen and m /z 253.1 /209.2 for ketoprofen (IS). Method validation included the evaluation of the matrix effect, extraction recovery, linearity, lower LOQ, within-run and between-run precision,stability and di-lution effect.Results The calibration curve was line-ar across the concentration range of 0.2 ~50 mg·L -1 for each ibuprofen enantiomer with a lower LOQ of 0.2 mg·L -1 .The within-run and between-run precision (RSD%)was in the range 1 .01 % ~1 3.1 % for each ibuprofen.The pharmacokinetic parameters for orally single dose of (S +)and racemic ibuprofen in Beagle dogs were as follows: Cmax , T1 /2 , AUC(0-t) were (82.98 ±1 4.83 )mg·L -1 ,(3.21 7 ±0.7298)h, (362.0 ±58.67)h·mg·L -1 for (S +)ibuprofen and 70.62 /74.48 mg·L -1 ,1 .520 /5.432 h ,1 77.8 /649.6 h·mg·L -1 for (R -)/(S +)ibuprofen,re-spectively.Conclusions A simple,rapid,accurate, high sensitivity and repeatability method has been suc-cessfully developed,which can analyze the concentra-tions of (R -)/(S +)ibuprofen in Beagle dog plasma simultaneously.The method could be applied for the investigation of pharmacokinetics of ibuprofen enanti-omers in Beagle dogs.关键词
布洛芬/LC-MS/MS/血药浓度/Beagle犬/药代动力学/对映异构体Key words
ibuprofen/LC-MS /MS/plasma concertra-tion/Beagle dogs/pharmacokinetics/enantiomers分类
医药卫生引用本文复制引用
赵秀红,夏媛媛,黄玉荣,张爱杰,魏广力,司端运..LC-MS／MS法测定Beagle犬血浆中布洛芬对映体的浓度[J].中国药理学通报,2015,(4):570-575,6.基金项目
国家科技部“重大新药创制”科技重大专项资助项目（No 2012ZX09304002）；天津市自然科学基金资助项目 （）
