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

Author(s):

Wenyan Luo, Hanzhi Zhang*, Ning Sun, Feng Qin and Hao Liu*   Pages 1 - 5 ( 5 )

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 any 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 METTA, and found that it was the amidation product of metaraminol and tartaric acid.

Conclusions: 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

Affiliation:

China State Institute of Pharmaceutical Industry, Shanghai,, Shanghai Institute for Food and Drug Control, Shanghai,, Shanghai Institute of Advanced Immunochemical Studies, ShanghaiTech University, Shanghai,, Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai,, Shanghai Institute for Food and Drug Control, Shanghai



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