Determination of process-related impurities in N-acetylglucosamine prepared by chemical and enzymatic methods: structural elucidation and quantification

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• 作者：Yi Soo Kim ; Sung Joong Lee ; Jin Young Choi ; Yun-Hi Kim…
• 刊名：Archives of Pharmacal Research
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：39
• 期：7
• 页码：937-945
• 全文大小：918 KB
• 刊物主题：Pharmacy; Pharmacology/Toxicology;
• 出版者：Springer Netherlands
• ISSN：1976-3786
• 卷排序：39

文摘

β-N-acetylglucosamine (β-AG) is a monosaccharide distributed widely in living organisms with various pivotal roles. The presence of particulates and impurities can affect the safety and efficacy of a product for its intended duration of use. Thus, the current study was carried out to identify and quantify the potentially-harmful process related impurities; namely α-N,6-diacetylglucosamine (α-DAG) and α-N-acetylglucosamine (α-AG), derived from the chemical and enzymatic synthesis of β-AG. The impurities were characterized using a high resolution mass spectrometry, a nuclear magnetic resonance spectroscopy, and liquid chromatography-tandem mass spectrometry (LC/MS/MS). The developed method showed a good linearity (R2 ≥ 0.998), satisfactory precision (≤6.1 % relative standard deviation), intra- and inter-day accuracy (88.20–97.50 %), extraction recovery (89.30–110.50 %), matrix effect (89.70–105.20 %), and stability (92.70–101.60 %). The method was successfully applied to determine the level of α-DAG that was 3.04 and 0.07 % of the total β-AG, following chemical and enzymatic methods, respectively. It can be concluded that the enzymatic rather than the chemical method is more efficient for the synthesis of β-AG. Characterization of impurities heeds the signal for acquiring and evaluating data that establishes biological safety.Keywordsβ-N-acetylglucosamineProcess-related impurityTandem mass spectrometryChitinNuclear magnetic resonance