Study of Impurity Profiles in Raw Materials and Tablets of Rutin and Its Production Process: Correlation Analysis

Abstract

An HPLC-UV method with high sensitivity and good resolution, calculated by the principal component external standard method with correction factors and detailed methodological validation according to ICH guidelines, was developed for the accurate detection of impurities in three different extraction processes of rutin raw materials and their tablets, and the determination of impurity profiles by LC-MS/MS. In this study, nine impurities (>0.1%) were mainly isolated and identified, four of which were process impurities, and the other five were degradation products. The results of the correlation between impurity profiles and production processes showed that the impurity content of rutin tablets correlated positively with the impurity level of the raw materials used, which correlated significantly with the extraction process. The finished rutin under the alkali-dissolution and acid-sedimentation refining method had low purity and the highest impurity content. In contrast, the number of impurities and the total amount of impurities detected in rutin by the secondary recrystallization process with methanol washing were the lowest, and were mainly process impurities. This further indicates that generating degradation impurities could be avoided, and a suitable refining process could effectively reduce impurities. This study provides an essential basis for manufacturers to optimize the process parameters of rutin raw materials.