摘要
目的：建立UPLC-MS/MS测定右旋酮洛芬氨丁三醇温敏水凝胶在大鼠体内的药动学特征。方法：采用Waters BEH C（18）（50 mm×2.1 mm,1.7μm）色谱柱,流动相为0.1%甲酸乙腈-0.1%甲酸水溶液,梯度洗脱;质谱采用电喷雾电离源（ESI）;扫描方式为多反应离子监测（MRM）。采用大鼠皮下注射水凝胶溶液、皮下注射药物溶液（0.9%Na Cl溶液）及灌胃（ig）3种方式给药后测定右旋酮洛芬氨丁三醇的血药浓度,并计算相关药动学参数。结果：注射水凝胶与注射溶液相比,C（max）有明显降低,T（max）较多延长;注射水凝胶与灌胃（ig）相比AUC0~∞有明显增加,同时C（max）有所降低,T（max）有所延长;且半衰期有明显增加。结论：该方法特异、快速、准确和灵敏,可用于右旋酮洛芬氨丁三醇温敏水凝胶在大鼠体内的药动学研究。
Objective： To develop a sensitive and reliable ultra performance liquid chromatography tandem mass sepctrometry（ UPLC-MS / MS） method for determination of dexketoprofen trometamol temperature-sensitive hydrogels in rat plasma,and investigate its pharmacokinetic characteristics. Methods： The dexketoprofen trometamol were simultaneously determined by UPLC-MS / MS on Waters BEH C（18） column（ 50 mm × 2. 1 mm,1. 7 μm）. The mobile phase,consisting of 0. 1% acetonitrile formic acid and 0. 1% aqueous formic acid,was programmed in a linear gradient mode. The compounds were ionized in the electrospray ionization ion source（ ESI） of the mass spectrometer and detected in MRM mode. The concentrations of dexketoprofen trometamol in plasma were analyzed after oral administration of dexketoprofen trometamol hydrogels,and subcutaneous injection of hydrogels solution and dexketoprofen saline solution,respectively. Then,the relevant pharmacokinetic parameters were calculated.Results： Compared with injection of drug solution,injection of drug hydrogels significantly reduced the C（max）,and extended T（max）. Compared with oral administration,hydrogel injection significantly increased AUC0 ~ ∞,reduced C（max）,extended T（max）,and increased t（1/2）. Conclusion： This method is specific,rapid,and sensitive; thus it may besuitable for pharmacokinetic studies of dexketoprofen trometamol temperature-sensitive hydrogelsl in rats.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2016年第8期923-927,共5页
Chinese Journal of New Drugs
基金
贵州省科学技术计划项目(黔科合LH字[2014]7081
黔科合重G字[2013]4001号)
贵阳市科技计划项目(筑科合同[20141001]05号)
贵州省高等学校创新能力提升计划(黔教合协同创新字[2013]04)
关键词
右旋酮洛芬氨丁三醇温敏水凝胶
药动学
液质联用法
dexketoprofen trometamol temperature sensitive hydrogels
pharmacokinetic
UPLC-MS /MS
