[1]刘静媛,武丽南,杨元辉,等.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,(03):411-416.[doi:10.3969/j.issn.1001-1978.2017.03.023]
 LIU Jing-yuan,WU Li-nan,YANG Yuan-hui,et al.Determination of halometasone and its pharmacokinetics study in rabbit plasma by LC-MS/MS[J].Chinese Pharmacological Bulletin,2017,(03):411-416.[doi:10.3969/j.issn.1001-1978.2017.03.023]
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LC-MS/MS法测定家兔血浆中卤米松浓度及其药动学研究()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2017年03期
页码:
411-416
栏目:
论著
出版日期:
2017-03-15

文章信息/Info

Title:
Determination of halometasone and its pharmacokinetics study in rabbit plasma by LC-MS/MS
文章编号:
1001-1978(2017)03-0411-06
作者:
刘静媛12武丽南2杨元辉2谷 元2魏广力2司端运2
1.天津医科大学研究生院,天津 300070;
2.天津药物研究院释药技术与药代动力学国家重点实验室,天津 300193
Author(s):
LIU Jing-yuan12 WU Li-nan2 YANG Yuan-hui2 GU Yuan2 WEI Guang-li2 SI Duan-yun2
1.Graduate School, Tianjin Medical University, Tianjin 300070,China;
2. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193,China
关键词:
卤米松 LC-MS/MS 家兔 药代动力学 血药浓度 经皮给药
Keywords:
halometasone LC-MS/MS rabbit pharmacokinetics plasma concentration dermal topical administration
分类号:
R-332;R452;R969.1;R977.11
DOI:
10.3969/j.issn.1001-1978.2017.03.023
文献标志码:
A
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 C18柱(100 mm×4.6 mm,5 μm)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 cm2)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0.02~20 μg·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Tmax、Cmax、AUC0-t、T1/2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。
Abstract:
Aim To develop and validate a LC-MS/MS assay to quantify halometasone in rabbit plasma and study pharmacokinetics of halometasone after dermal topical administration of Halometasone Cream.Methods The plasma sample was submitted to liquid-liquid extraction using methyl tertiary butyl ether, with dexamethasone as the internal standard(IS). Chromatographic separations were performed on a Diamonsil C18 column(100 mm×4.6 mm, 5 μm)with a linear gradient of methanol and 2 mmol·L-1 ammonium acetate. Halometasone and dexamethasone(IS)were ionized with an ESI source operated in negative ion mode, and the detected ions were m/z 503.1→413.0(halometasone), 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 using a validated LC-MS/MS assay.Results Calibration curve was linear over the concentration range of 0.02~20 μg·L-1 in rabbit plasma. For low, medium, 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 This LC-MS/MS analysis method has high sensitivity, and sample processing method is simple, which has been rigorously validated. The method could be successfully applied to the pharmacokinetic study of halometasone after skin administration of Halometasone Cream to rabbits.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金青年基金项目(No 81503154)
作者简介:刘静媛(1991-),女,硕士生,研究方向:药代动力学,E-mail: tyliujy8070@163.com;
司端运(1965-),男,博士,研究员,研究方向:药代动力学,通讯作者,E-mail:sidy@tjipr.com
更新日期/Last Update: 2017-03-15