中国药理学通报2017，Vol.33Issue(3)：411-416,6.DOI:10.3969/j.issn.1001-1978.2017.03.023
LC-MS/MS法测定家兔血浆中卤米松浓度及其药动学研究
Determination of halometasone and its pharmacokinetics study in rabbit plasma by LC-MS/MS
摘要
Abstract
Aim TodevelopandvalidateaLC-MS/MS assay to quantify halometasone in rabbit plasma and study pharmacokinetics of halometasone after dermal topical administration of Halometasone Cream.Meth-ods Theplasmasamplewassubmittedtoliquid-liquid extraction using methyl tertiary butyl ether,with dexa-methasone as the internal standard (IS ).Chromato-graphic separations were performed on a Diamonsil C18 column(100 mm ×4. 6 mm,5 μm)with a linear gra-dient of methanol and 2 mmol · L-1 ammonium ace-tate.Halometasone and dexamethasone(IS)were ion-ized with an ESI source operated in negative ion mode, and the detected ions were m/z 503. 1→413. 0 (halo-metasone),m/z 391. 0→361. 0 (dexamethasone ). The test article could be monitored in rabbit plasma when following single dermal topical administration of Halometasone Cream at 1 g/100 cm2 to rabbits by u-singavalidatedLC-MS/MSassay.Results Calibra-tion curve was linear over the concentration range of0. 02~20 μg·L-1 in rabbit plasma.For low,medi-um,high concentration of QC solutions,the intra-and inter-day precision was in the range of 3. 72% ~7. 87%, and the accuracy was within 99. 1% to 103%. The pharmacokinetic parameters in rabbits were as follows:Tmax,Cmax,AUC0-t,T1/2 was (7. 38 ± 1. 06)h,(1. 16 ±0. 527)μg·L-1,(18. 8 ±7. 23)h·μg·L-1 ,(13. 8 ±3. 70)h,respectively.Conclusions ThisLC-MS/MSanalysismethodhashighsensitivi-ty,and sample processing method is simple,which has been rigorously validated.The method could be suc-cessfully applied to the pharmacokinetic study of halo-metasone after skin administration of Halometasone Cream to rabbits.关键词
卤米松/LC-MS/MS/家兔/药代动力学/血药浓度/经皮给药Key words
halometasone/LC-MS/MS/rabbit/pharma-cokinetics/plasma concentration/dermal topical admin-istration分类
医药卫生引用本文复制引用
刘静媛,武丽南,杨元辉,谷元,魏广力,司端运..LC-MS/MS法测定家兔血浆中卤米松浓度及其药动学研究[J].中国药理学通报,2017,33(3):411-416,6.基金项目
国家自然科学基金青年基金项目(No 81503154) （No 81503154）
