Characterisation of degradation products of tegoprazan by LC-MS and GC-MS

Kaijing Guo; Xiao He; Hongyi Zhao; Chen Ma

doi:10.1016/j.jpba.2023.115323

Characterisation of degradation products of tegoprazan by LC-MS and GC-MS

J Pharm Biomed Anal. 2023 May 10:228:115323. doi: 10.1016/j.jpba.2023.115323. Epub 2023 Mar 4.

Authors

Kaijing Guo¹, Xiao He¹, Hongyi Zhao¹, Chen Ma²

Affiliations

¹ Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
² Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China. Electronic address: mach@imm.ac.cn.

PMID: 36921447
DOI: 10.1016/j.jpba.2023.115323

Abstract

Tegoprazan is a novel orally active potassium-competitive acid blocker (P-CAB), capable of binding to the K⁺ binding site of H⁺/K⁺-ATPase in a reversible way to inhibit gastric acid secretion. Tegoprazan has been approved for treating acid-related diseases. In this study, stress testings of tegoprazan were performed under various conditions, including hydrolysis (acidic, alkaline, and neutral), oxidation, photolysis, and thermal stress. Tegoprazan showed instability in acidic, alkaline, and oxidative conditions. Eight degradation products (DPs) were identified. The DPs were characterized by LC-HRMS, LC-MSⁿ, or GC-Q-TOF-MS. Meanwhile, DP-1, DP-2 and DP-3 were successfully synthesized and confirmed by NMR. The degradation pathway of tegoprazan was summarized. To the best of our knowledge, this is the first study on the forced degradation of tegoprazan.

Keywords: GC-Q-TOF-MS; LC-HRMS; LC-MS(n); NMR; Stress testing; Tegoprazan.

MeSH terms

Chromatography, High Pressure Liquid
Chromatography, Liquid
Drug Stability
Gas Chromatography-Mass Spectrometry
Hydrolysis
Oxidation-Reduction
Photolysis
Tandem Mass Spectrometry*

Substances

tegoprazan