摘要
目的建立测定家兔血浆中卤米松浓度的LC-MS/MS方法,研究卤米松乳膏经皮给药后家兔体内卤米松的药代动力学特征。方法以地塞米松为内标,血浆样品采用甲基叔丁基醚液-液萃取的处理方法,以Diamonsil C_(18)柱(100 mm×4.6 mm,5μm)分离,甲醇、2 mmol·L-1乙酸铵为流动相进行梯度洗脱,通过电喷雾电离源进行负离子检测,检测离子对为m/z 503.1→413.0(卤米松),m/z 391.0→361.0(地塞米松,内标);以经过严格方法学验证的LC-MS/MS法测定家兔单次经皮给药(1 g/100 cm^2)后血浆中卤米松的浓度。结果家兔血浆中卤米松的线性范围为0.02~20μg·L^(-1),低、中、高质控浓度的批内、批间精密度(RSD)介于3.72%~7.87%之间,准确度在99.1%~103%之间。家兔单次经皮给予卤米松乳膏后的主要药代动力学参数T_(max)、C_(max)、AUC_(0-t)、T_(1/2)分别为:(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。结论该LC-MS/MS分析方法灵敏度高且样品处理方法简便,通过了严格的方法学验证,可用于卤米松乳膏皮肤给药后,家兔体内卤米松的药代动力学研究。
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.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2017年第3期411-416,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金青年基金项目(No 81503154)
关键词
卤米松
LC-MS/MS
家兔
药代动力学
血药浓度
经皮给药
halometasone
LC-MS/MS
rabbit
pharma-cokinetics
plasma concentration
dermal topical admin-istration
