Characterization of a New Impurity in Metaraminol Bitartrate for Injec-tion by 2D HPLC-Q/TOF-MS, Chemical Synthesis and NMR

Background: Impurities in pharmaceutical compounds can influence their clinical ef-fects and represent a potential health risk. To ensure the safety and effectiveness of a drug, it is ne-cessary 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 spectrome-try (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 chromatograph-ic system, which was connected to the mass spectrometer. We obtained MET-TA by chemical syn-thesis, and its structure was characterized by MS/MS and further confirmed by nuclear magnetic re-sonance (NMR). Results: The impurity was found to be (2S, 3S)-2,3.-dihydroxy-4-((1R,2S)-1-hydroxy-1-(3-hydrox-yphenyl)propan-2-yl)amino)-4-oxobutanoic acid, labelled as MET-TA. In this study, we investigat-ed the mechanism of formation of MET-TA, and found that it was the amidation product of me-taraminol 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.