title: Matrix precipitation: a general strategy to eliminate matrix interference for pharmaceutical toxic impurities analysis.
abstract: Matrix interference, which can lead to false positive/negative results, contamination of injector or separation column, incompatibility between sample solution and the selected analytical instrument, and response inhibition or even quenching, is commonly suffered for the analysis of trace level toxic impurities in drug substance. In this study, a simple matrix precipitation strategy is proposed to eliminate or minimize the above stated matrix interference problems. Generally, a sample of active pharmaceutical ingredients (APIs) is dissolved in an appropriate solvent to achieve the desired high concentration and then an anti-solvent is added to precipitate the matrix substance. As a result, the target analyte is extracted into the mixed solution with very less residual of APIs. This strategy has the characteristics of simple manipulation, high recovery and excellent anti-interference capability. It was found that the precipitation ratio (R, representing the ability to remove matrix substance) and the proportion of solvent (the one used to dissolve APIs) in final solution (P, affecting R and also affecting the method sensitivity) are two important factors of the precipitation process. The correlation between R and P was investigated by performing precipitation with various APIs in different solvent/anti-solvent systems. After a detailed mathematical reasoning process, P=20% was proved to be an effective and robust condition to perform the precipitation strategy. The precipitation method with P=20% can be used as a general strategy for toxic impurity analysis in APIs. Finally, several typical examples are described in this article, where the challenging matrix interference issues have been resolved successfully.
authors.affiliation: HEC Research and Development Center, HEC Pharm Group, Dongguan 523871, PR China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yang
authors.affiliation: HEC Research and Development Center, HEC Pharm Group, Dongguan 523871, PR China.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Xiong
authors.affiliation: HEC Research and Development Center, HEC Pharm Group, Dongguan 523871, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Cao
authors.affiliation: HEC Research and Development Center, HEC Pharm Group, Dongguan 523871, PR China.
authors.forename: Baolei
authors.initials: B
authors.lastname: Luan
authors.affiliation: HEC Research and Development Center, HEC Pharm Group, Dongguan 523871, PR China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: HEC Research and Development Center, HEC Pharm Group, Dongguan 523871, PR China. Electronic address: liuguozhu@hecpharm.com.
authors.forename: Guozhu
authors.initials: G
authors.lastname: Liu
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D004340:Drug Contamination / Q000517:prevention & control; D004345:Drug Industry / Q000379:methods*; D015386:Hazardous Substances / Q000032:analysis*; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
chemical_list: D015386:Hazardous Substances; D004364:Pharmaceutical Preparations; D012996:Solutions; D012997:Solvents
keywords: Drug substance; Matrix interference; Matrix precipitation; Toxic impurity analysis