重氮化法测定小鼠血清对乙酰氨基酚浓度及其在评价胃排空功能中的.pdfVIP

氮化法测定小鼠血清对乙酰氨基酚浓度及其在评价胃排空功能中的应用 李彩娜，孙素娟，申竹芳 （中国医学科学院、北京协和医学院药物研究所，天然药物活性物质与功能国家 重点实验室 北京 100050） 【摘要】 建立血清对乙酰氨基酚浓度的测定方法，用于评价胃排空功能。对乙 酰氨基酚水解后与亚硝酸发生重氮化反应，所得产物在312 nm 处具有特征吸收 峰，绘制标准曲线，计算血清对乙酰氨基酚浓度和回收率。ICR 小鼠灌胃对乙酰 氨基酚（500 mg kg-1 ），动态测定其血药浓度；用该方法评价小鼠皮下注射长效 GLP-1 类似物GW002 对胃排空的影响。对乙酰氨基酚在0-160 μg mL-1 内发生重 氮化反应的线性关系良好 （R2 = 0.9997 ）；以该方法测定血清对乙酰氨基酚浓度 的线性也较好 （R2 = 0.9982 ），回收率为97.4%-116.7% 。对乙酰氨基酚灌胃后血 药浓度于0.5 h 达峰。GW002 能够明显降低小鼠血清对乙酰氨基酚浓度，使药时 曲线下面积（AUC ）降低28.4% 。本研究建立了一种测定血清对乙酰氨基酚浓度 的方法，具有良好的准确性，可用于评价小鼠的胃排空功能。 【关键字】 对乙酰氨基酚；重氮化反应；胃排空 中图分类号：R965 Determination of serum acetaminophen based on the diazo reaction and its application in the evaluation of gastric emptying LI Cai-na, SUN Su-juan, SHEN Zhu-fang* (State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beij ing 100050, China) 【Abstract 】This study aims to establish a method to determine the serum acetaminophen concentration based on the diazo reaction, and apply it in the gastric emptying evaluation. In theory, acetaminophen could take hydrolysis reaction in hydrochloric acid solution to produce P-aminophenol, which could then take diazo 收稿日期：2014-10-20；修回日期：2014-12-25. 基金项目：重大新药创制（2012Z004 ）. 通讯作者Tel/ Fax：010 Email：shenzhf@imm.ac.cn 1 reaction resulting in a product with special absorption peak at 312 nm. Then the serum acetaminophen concentration and recovery rate were calculated according to the standard curve drawn with absorbance at 312 nm. ICR mice were given a dose of acetaminophen (500 mg kg-1) by gavage and the serum acetaminophen was dynamically measured through the diazo reaction. Besides, ICR mice were subcut