Characterization of an Unknown Impurity in Glucosamine Sulfate Sodium Chloride by HPLC-Q-TOF MS and NMR

Author(s): Miao Zhang, Peixi Zhu, Yue Chen, Weifang Ni, Yu Li*, Liya Hong*.

Journal Name: Current Pharmaceutical Analysis

Volume 15 , Issue 6 , 2019

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Graphical Abstract:


Abstract:

Background: Glucosamine sulfate sodium chloride (glucosamine-SP) is mainly used for the treatment of osteoarthritis. During quality control of glucosamine-SP capsules, an unknown impurity was detected. Another unknown degradation product was generated together with above-mentioned impurity in heat condition.

Objective: The study aimed to characterize an unknown impurity in glucosamine-SP capsules.

Methods: A new volatile HPLC method compatible with mass spectrometry detection was set up. An amino column at 35 °C with a mobile phase consisting of water and acetonitrile (20: 80, v/v) was used at a flow rate of 1.5 ml/min at 297 nm. High-performance liquid chromatography quadrupole time-offlight mass spectrometry (HPLC-Q-TOF MS) was used to identify the impurity with the electrospray ionization (ESI) source in the positive ionization mode.

Results: The results of HPLC-Q-TOF MS analysis indicated that the protonated molecule ions [M + H]+ of the unknown impurity and the novel degradation product were both at m/z 287. Preparative LC method was put into practice with a Prep-C18 column with a mobile phase consisting of water and acetonitrile (99: 1, v/v) at a flow rate of 20.0 ml/min at 297 nm. The assignment of the 1D and 2D NMR signals was performed for the unknown impurity. In addition, the formation of impurities was also studied.

Conclusion: An unknown impurity and a degradation product in glucosamine-SP capsules were characterized. They were assigned as (1R, 2S, 3R)-1-(5-((S, E)-3, 4-dihydroxybut-1-en-1-yl) pyrazin-2-yl) butane-1, 2, 3, 4-tetraol and (1R, 2S, 3R)-1-(5-((S, Z)-3, 4-dihydroxybut-1-en-1-yl) pyrazin-2-yl) butane- 1, 2, 3, 4-tetraol.

Keywords: Glucosamine sulfate sodium chloride, HPLC-Q-TOF mass spectrometry, unknown impurity, degradation product, preparative liquid chromatography, nuclear magnetic resonance (NMR).

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Article Details

VOLUME: 15
ISSUE: 6
Year: 2019
Page: [650 - 660]
Pages: 11
DOI: 10.2174/1573412915666190222160957
Price: $65

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