一种经过验证的、灵敏的高效液相色谱法，用于测定对乙酰氨基酚原料药中的痕量杂质。

A validated, sensitive HPLC method for the determination of trace impurities in acetaminophen drug substance.

作者信息

Kamberi Marika, Riley Christopher M, Ma Sharon Xiaoyan, Huang Chen Wen C

机构信息

Department of Analytical Sciences, ALZA Corporation, Mountain View, 1501 California Avenue, Palo Alto, CA 94304, USA.

出版信息

J Pharm Biomed Anal. 2004 Jan 27;34(1):123-8. doi: 10.1016/j.japna.2003.08.015.

DOI:10.1016/j.japna.2003.08.015

PMID:14738926

Abstract

A high-performance liquid chromatography (HPLC) method has been developed and validated for the simultaneous determination of n-propionyl-p-aminophenol, 3-chloro-4-hydroxyacetanilide, 4'-hydroxyacetophenone, 4-hydroxyacetophenone oxime, 4-acetoxyacetanilide and 4'-chloroacetanilide, the main impurities in acetaminophen drug substance. The chromatographic separation was achieved on an Eclipse XDB-18 reversed-phase column using a gradient elution, being solvent A: 0.01 M phosphate buffer at pH 3.0 and solvent B: methanol. The limit of quantitation (S/N=10:1) was 0.1 microg/ml for each impurity. The coefficients of variation were less than 4% for intra-day and inter-day analyses. The individual recovery of acetaminophen spiked samples ranged from 94 to 104% and the mean recovery for each level from 99 to 103% in the 1-150 microg/ml range for all impurities. The proposed method was successfully applied to the analyses of different lots and different manufactures of acetaminophen drug substance. The proposed method can be used for the routine quality control of acetaminophen.

摘要

已开发并验证了一种高效液相色谱（HPLC）方法，用于同时测定对乙酰氨基酚原料药中的主要杂质正丙酰对氨基酚、3-氯-4-羟基乙酰苯胺、4'-羟基苯乙酮、4-羟基苯乙酮肟、4-乙酰氧基乙酰苯胺和4'-氯乙酰苯胺。采用梯度洗脱，在Eclipse XDB-18反相柱上实现色谱分离，溶剂A为pH 3.0的0.01 M磷酸盐缓冲液，溶剂B为甲醇。每种杂质的定量限（S/N = 10:1）为0.1 μg/ml。日内和日间分析的变异系数均小于4%。在1 - 150 μg/ml范围内，对乙酰氨基酚加标样品中各杂质的回收率在94%至104%之间，各水平的平均回收率在99%至103%之间。该方法成功应用于不同批次和不同厂家的对乙酰氨基酚原料药分析。该方法可用于对乙酰氨基酚的常规质量控制。