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酒石酸长春瑞滨长循环(热敏)脂质体在比格犬体内的药代动力学研究

刘楠 龚伟 张慧 喻芳邻 李迎 李明媛 梅兴国

军事医学Issue(9):698-701,4.
军事医学Issue(9):698-701,4.DOI:10.7644/j.issn.1674-9960.2015.09.012

酒石酸长春瑞滨长循环(热敏)脂质体在比格犬体内的药代动力学研究

Pharmacokinetics study of long-circulation and thermosensitive liposome loaded vinorelbine bitartrate in beagle dogs

刘楠 1龚伟 1张慧 1喻芳邻 1李迎 1李明媛 1梅兴国1

作者信息

  • 1. 军事医学科学院毒物药物研究所,北京 100850
  • 折叠

摘要

Abstract

Objective To establish a quick method to analyze vinorelbine ( NVB) in plasma of beagle dogs and study its pharmacokinetics of long-circulation and thermosensitive liposome loaded vinorelbine bitartrate.Methods The plasma was treated with liquid-liquid extraction after precipitation in methanol.The analysis was perfomed on a Venusil XBP C18 column(2.1 mm ×50 mm, 3 μm) at 35℃,the mobile phase consisted of methanol and water( containing 10 mmol/L ammonium acetate, 1%acetonitrile) 80∶20 and injection volume was 10μl.The type of mass spectrum was multireactive monitoring(MRM) in a positive mode.The monitor transitions were m/z 779.4-765.4 for vinorelbine and m/z 825.4-122 for vincristine.Results The concentration range from 10 to 2500 ng/ml had a good linearity ( r=0.0994).The precision, accuracy and extraction efficiency were acceptable.The plasma samples were stable for 10 days at -20℃ and 24 h at room temperature.Pharmacokinetic study in beagle dogs showed that the main parameters for injection and liposome were Cmax(833.51 ±150.42) and (1397.95 ±443.05)ng/ml, AUC(0-t) (577.16 ±223.57) and (1059.82 ±408.27) ng/ml· h, Cl(3014.64 ±1049.17)and 1633.10 ±551.77 ml/(h· kg), respectively.Conclusion A reliable HPLC-MS/MS method for vinorelbine analysis is established and can be applied to the pharmacokinetics study of liposome.The results show that liposome has a higher AUC, Cmax and longer Cl than injection.Meanwhile, liposome has a lower irritability.

关键词

液质联用/长春瑞滨/长循环热敏脂质体/药代动力学

Key words

HPLC-MS/MS/vinorelbine/long-circulation and thermosensitive liposome/pharmacokinetics

分类

医药卫生

引用本文复制引用

刘楠,龚伟,张慧,喻芳邻,李迎,李明媛,梅兴国..酒石酸长春瑞滨长循环(热敏)脂质体在比格犬体内的药代动力学研究[J].军事医学,2015,(9):698-701,4.

基金项目

国家科技重大专项资助项目 ()

军事医学

OA北大核心CSCDCSTPCD

1674-9960

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