Citation: LIU Xuewei, LI Cheng, HAN Haiyun, ZHANG Wenpeng, CHEN Dongying. Advances on genotoxic impurities of sulfonate esters in pharmaceuticals[J]. Chinese Journal of Chromatography, ;2018, 36(10): 952-961. doi: 10.3724/SP.J.1123.2018.05004 shu

Advances on genotoxic impurities of sulfonate esters in pharmaceuticals

LIU Xuewei ^1,2, ,
LI Cheng ³ ,
HAN Haiyun ¹ ,
ZHANG Wenpeng ^1,2 ,
CHEN Dongying ^1,2

1.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
2.
University of Chinese Academy of Sciences, Beijing 100049, China;
3.
Shanghai Center for Drug Evaluation and Inspection, Shanghai 201203, China

Received Date: 3 May 2018

Fund Project: Chinese Academy of Sciences for Innovative Pharmaceutical Project (No. CASIMM0120163011).

This article reviews the refinement of regulatory guidelines and progress of research on the control of genotoxic impurities in pharmaceuticals in the last decade. It outlines advances in the regulatory requirements for genotoxic impurities from strict avoidance to the currently accepted concept of threshold of toxicological concern (TTC), which is based on risk control considerations. Specific control limits, which are required by predominant administrative regulatory agencies, such as U. S. Food and Drug Administration (FDA), European Medicines Agency (EMA) and the international conference on harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH), etc. Sulfonate esters, an important class of potential genotoxic impurities, are usually generated by side-reactions between sulfonic acids or their derivatives and relative low molecular mass alcohols, such as methanol, ethanol, and isopropanol. The resulting sulfonate esters are characterized with diverse chemical structures. Reaction mechanisms of the formation of sulfonate esters and various strategies to control them have been schematically described. A detailed summary has been given for the analytical methodology developed using high performance liquid chromatography (HPLC) and gas chromatography (GC) to determine trace amounts of sulfonate esters in pharmaceuticals. Furthermore, we have comprehensively discussed the options for the chromatographic methods, sample pretreatments, and derivatization methods, as well as each method's sensitivity and recovery at trace level. This review intended to provide constructive suggestions for the rational control of sulfonate esters in pharmaceuticals to ensure their clinical safety.
- genotoxic impurity,
- sulfonate ester,
- control strategy,
- chromatographic method,
- review
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