Isolation and structure characterization of related impurities in etimicin sulfate by LC/ESI-MS(n) and NMR

J Pharm Biomed Anal. 2011 Jul 15;55(5):902-7. doi: 10.1016/j.jpba.2011.03.005. Epub 2011 Mar 8.

Abstract

Etimicin sulfate is a semi-synthetic aminoglycoside which is modified from gentamicin C1a, used as an antibiotic effective both to Gram-positive and Gram-negative bacteria infections. Ten impurities were detected in the bulk drug by LC-ELSD and LC-ESI-MS(n). Weakly acidic cation exchange resin, CM-sephadex and silica gel column chromatography were used for the isolation of six impurities. Based on LC/ESI-MS(n) and NMR analysis, related impurities were characterized as gentamicin C1a (1), 1-N-ethyl garamine (2), 2″-N-ethyl gentamicin C1a, or 6″-N-ethyl gentamicin C1a (3), 1-N-ethyl-3'-N-demethyl gentamicin C2b (4), 3-N-ethyl gentamicin C1a (5), 6″-deamino-6″-hydroxyl etimicin (6), 1,3-N, N-diethyl garamine (7), 1-N-ethyl gentamicin C2b (8), 2″ or 6″-N-ethyl etimicin (9), 1,3-N, N-diethyl gentamicin C1a (10). 10 is a new aminoglycoside, the (1)H and (13)C NMR data of compounds 5-7, 10 are first reported in the paper. The possible mechanism for the formation of impurities is also discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemistry Techniques, Analytical / methods
  • Chemistry, Pharmaceutical / methods*
  • Chromatography, Liquid / methods*
  • Gentamicins / analysis*
  • Gentamicins / chemistry
  • Magnetic Resonance Spectroscopy / methods*
  • Models, Chemical
  • Reproducibility of Results
  • Spectrometry, Mass, Electrospray Ionization / methods*

Substances

  • Gentamicins
  • etimicin sulfate