Structural Identification of Impurities in Pioglitazone Hydrochloride Preparations by 2D-UHPLC-Q-Exactive Orbitrap HRMS and Their Toxicity Prediction

Dandan Zhang; Weijian Wang; Haiyun Zhao; Song Wang; Mingyan Yu; Dongmei Zhang; Wenkun Liu; Qiangsheng Xie; Dejun Chen

doi:10.1155/2023/2096521

Structural Identification of Impurities in Pioglitazone Hydrochloride Preparations by 2D-UHPLC-Q-Exactive Orbitrap HRMS and Their Toxicity Prediction

Int J Anal Chem. 2023 Oct 17:2023:2096521. doi: 10.1155/2023/2096521. eCollection 2023.

Authors

Dandan Zhang¹, Weijian Wang¹, Haiyun Zhao¹, Song Wang¹, Mingyan Yu¹, Dongmei Zhang¹, Wenkun Liu¹, Qiangsheng Xie¹, Dejun Chen¹

Affiliation

¹ Shandong Institute for Food and Drug Control, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Public Service Platforms for Industrial Technology, Jinan, China.

Abstract

Pharmaceutical companies and regulatory agencies have more and more concerns for impurities in pharmaceuticals and their toxicity. In this work, heart-cutting two-dimensional ultrahigh-performance liquid chromatography (2D-UHPLC) in combination with high-resolution mass spectrometry (HRMS) was used, setting HRMS as positive mode of electrospray ionization to identify five impurities in pioglitazone hydrochloride preparations. With the heart-cutting 2D-UHPLC and online desalting technique, the structures of five impurities were deduced in an analysis of MSⁿ data. And three of them, Impurity-2, Impurity-3, and Impurity-5, have never been reported before. The fragmentation patterns of five impurities were proposed on a basis of accurate mass and fragment ions in this study. Since the toxicity of impurities is relevant to their structures, toxicology of all five impurities was predicted by three software tools, and the result showed that these compounds have good safety profile.