Abstract

Background: Impurities in pharmaceutical compounds can influence their clinical effects and represent a potential health risk. To ensure the safety and effectiveness of a drug, it is necessary to investigate potential impurities.

Methods: In this paper, a new impurity was separated and characterized by two-dimensional high performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (2D HPLC-Q/TOF-MS) in negative electrospray ionization mode. The peak containing the new impurity, eluted from the first dimension chromatographic system, was selectively trapped by a switching valve based on its retention time and transferred to the second dimension chromatographic system, which was connected to the mass spectrometer. We obtained MET-TA by chemical synthesis, and its structure was characterized by MS/MS and further confirmed by nuclear magnetic resonance (NMR).

Results: The impurity was found to be (2S, 3S)-2,3.-dihydroxy-4-((1R,2S)-1-hydroxy-1-(3-hydroxyphenyl) propan-2-yl)amino)-4-oxobutanoic acid, labelled as MET-TA. In this study, we investigated the mechanism of formation of MET-TA, and found that it was the amidation product of metaraminol and tartaric acid.

Conclusion: The identification, structural elucidation, synthesis and most probable mechanism of formation of MET-TA are discussed in detail in this paper.

Keywords: Metaraminol bitartrate injection, impurity, chemical synthesis, identification, 2D HPLC-Q/TOF-MS, quality control.

Graphical Abstract