title: Isolation and structure characterization of related impurities in etimicin intermediate P1 by LC/ESI-MS(n) and NMR.
abstract: Etimicin intermediate 3,2″,6″-N,N,N-triacetyl gentamicin C1a (P1), is a key intermediate of etimicin, which is a semi-synthetic aminoglycoside antibiotic effective to both gram-positive and gram-negative bacteria infections. Four major related impurities of P1 were detected by HPLC-ELSD and ESI-MS(n) methods. Weakly acidic cation exchange resin, CM-sephadex and silica gel column chromatography were used for the isolation and purification of four major impurities. By means of ESI-MS(n) and NMR analysis, related impurities were characterized as 3,2″-N,N-diacetyl gentamicin C1a (1), 3,2″,6″-N,N,N-triacetyl gentamicin C2b (2), 2″-N-acetyl gentamicin C1a (3), and 2″,6″-N,N-diacetyl gentamicin C1a (4). Impurities 1, 2, 4 are novel compounds and the NMR data of these isolates were first reported in this paper. The possible mechanism for the formation of these impurities is also discussed.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Wuxi Jiminkexin Shanhe Pharmaceutical Company limited, Wuxi 214028, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, China.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: wanghao@cpu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, China.
authors.forename: Wencai
authors.initials: W
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry; D002853:Chromatography, Liquid; D004340:Drug Contamination; D005839:Gentamicins / Q000737:chemistry* / Q000302:isolation & purification*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000617:Aminoglycosides; D005839:Gentamicins; C448680:etimicin
keywords: Etimicin; Intermediate P1; LC/ESI-MS(n); NMR; Related impurities