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采用液相色谱-串联质谱法测定各种生物基质中的丙烯酰胺和缩水甘油酰胺及其在药代动力学研究中的应用。

Determination of acrylamide and glycidamide in various biological matrices by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

机构信息

School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Korea.

Department of Pharmacy, Wonkwang University, Iksan, Jeonbuk, Korea.

出版信息

Talanta. 2015 Jan;131:46-54. doi: 10.1016/j.talanta.2014.07.042. Epub 2014 Jul 24.

DOI:10.1016/j.talanta.2014.07.042
PMID:25281071
Abstract

Acrylamide (AA) is a heat-generated food toxicant formed when starchy foods are fried or baked. This study describes a simple and sensitive liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of AA and its active metabolite, glycidamide (GA) in rat plasma, urine, and 14 different tissues. The assay utilized a simple method of protein precipitation and achieved a lower limit of quantification of 5, 10 and 25 ng/mL of AA and 10, 20 and 100 ng/mL of GA for plasma, tissues and urine, respectively. The assay was fully validated to demonstrate the linearity, sensitivity, accuracy, precision, process recovery, and stability using matrix matched quality control samples. The mean intra- and inter-day assay accuracy was 91.6-110% for AA and 92.0-109% for GA, and the mean intra- and inter-day assay precisions were ≤ 10.9% for AA and ≤ 8.60% for GA. The developed method was successfully applied to a pharmacokinetic study of AA and GA following intravenous and oral administration of AA in rats. Tissue distribution characteristics of AA and GA were also determined under steady-state conditions.

摘要

丙烯酰胺(AA)是一种热生成的食物毒物,当淀粉类食物煎炸或烘烤时会形成。本研究描述了一种简单灵敏的液相色谱-串联质谱法,用于同时定量检测大鼠血浆、尿液和 14 种不同组织中的 AA 及其活性代谢物丙烯醛(GA)。该测定法采用了简单的蛋白沉淀方法,血浆、组织和尿液中 AA 的定量下限分别为 5、10 和 25ng/mL,GA 的定量下限分别为 10、20 和 100ng/mL。采用基质匹配的质控样品对该测定法进行了全面验证,以证明其线性、灵敏度、准确性、精密度、过程回收率和稳定性。AA 的日内和日间测定准确度的平均值为 91.6-110%,GA 的为 92.0-109%,AA 的日内和日间测定精密度的平均值均≤10.9%,GA 的均≤8.60%。该方法成功地应用于 AA 静脉和口服给药后 AA 和 GA 的药代动力学研究。还在稳态条件下确定了 AA 和 GA 的组织分布特征。

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