柱前衍生-高效液相色谱荧光法测定人血浆中乙酰半胱氨酸及其生物等效性研究  

Determination of N-acetylcysteine in human plasma by precolumn derivatization and HPLC-FLD method and study on its bioequivalence

作　　者：张乐[1] 胡岚岚[1] 周世文[1] 汤建林[1] 

机构地区：[1]第三军医大学新桥医院国家药物临床试验机构,重庆400037

出　　处：《中国测试》2013年第2期52-55,共4页China Measurement & Test

摘　　要：建立一种快速、准确测定人血浆中乙酰半胱氨酸(N-acetylcysteine,NAC)含量的柱前衍生-高效液相色谱荧光法,并使用该方法对NAC不同剂型间的人体生物等效性进行研究。以NAC与N-(1-芘)马来酰亚胺(N-(1-Pyrenyl)maleimide,NPM)进行衍生化反应后进样测定;采用Diamonsil C18色谱柱(5μm×150 mm×4.6 mm)分离,流动相组成为:乙腈-10mmol·L-1NaH2PO(4含TMA 10mmol·L-1,H3PO4调pH至3.4)为50∶50。采用上述方法测定人血浆中NAC浓度,计算药物动力学参数并进行生物等效性评价。NAC 0.1～6.58μg·mL-1的浓度范围内呈良好线性,血浆中NAC定量下线为0.1μg·mL-1,方法回收率在85.3%-103.3%之间,日内、日间RSD均小于15%。该方法准确、快速、灵敏,可用于NAC的治疗药物监测、人体内药代动力学及生物等效性研究,两种制剂生物等效。To establish an HPLC and fluorescent detection method with N-（1-Pyrenyl） maleimide（NPM） as a pre-column derivatization reagent to determine N-acetylcysteine（NAC） in human plasma and study on its bioequivalence in Chinese healthy volunteers.The analytes were separated on a Diamonsil C18 column（5 μm ×150 mm ×4.6 mm） using 10 mmol·L-1 NaH2PO4 aqueous solution including 10 mmol·L-1 TMA and acetonitrile（50∶50） as a mobile phase at a flow rate The plasma concentration was determined by the method mentioned above.As a result the calibration curve was found to be linear over a range of 0.1-6.58 μg·mL-1,and the limit of the quantitation was 0.1 μg·mL-1.The recovery of the method ranged from 85.3%-103.3%.The coefficients of variation for inter-day and intra-day precisions were both15%.As an accurate,rapid and sensitive method,this assay has been successfully applied in the therapeutic drug monitoring,and the study of pharmacokinetic and bioavailability of NAC.The test preparation and the reference preparation are bioequivalence.

关 键 词：乙酰半胱氨酸 HPLC N-苯基马来酰亚胺 柱前衍生化 生物等效性 

分 类 号：R331[医药卫生—人体生理学] Q592.1[医药卫生—基础医学]