Investigation of unknown related substances in commercial erythromycin samples with liquid chromatography/mass spectrometry

Abstract

A selective reversed phase liquid chromatography/mass spectrometry (LC/MS(n)) method is described for the identification of erythromycin impurities and related substances in commercial erythromycin samples. Mass spectral data are acquired on a LCQ ion trap mass spectrometer equipped with an electrospray interface operated in positive ion mode. The LCQ is ideally suited for identification of impurities and related substances because it provides on-line LC/MS(n) capability. Compared with UV detection, this hyphenated LC/MS(n) technique provides as a main advantage efficient identification of novel substances without time-consuming isolation and purification procedures. Using this method four novel related substances were identified in commercial samples.

Analysis of unknown compounds in azithromycin bulk samples with liquid chromatography coupled to ion trap mass spectrometry

“…It is supposed that, in the context of biosynthetic routes, the ethyl side chain was replaced by a propyl side chain during fermentation. An analogous impurity was identified earlier in erythromycin samples 5. The proposed structure for U 4 is 13‐propyl‐13‐desethyl‐azithromycin A.…”

“…Recently, four other related substances have been reported to be present in bulk erythromycin samples by Govaerts et al . :5 13‐methyl‐13‐desethyl‐erythromycin C, 13‐methyl‐13‐desethyl‐erythromycin A, 13‐propyl‐13‐desethyl‐erythromycin A and a fourth compound, having an aberrant sugar moiety. Since azithromycin is obtained from erythromycin, impurities present will undergo the same modifications and the azithromycin analogues of these impurities can be found in azithromycin bulk samples.…”

Multi‐stage mass spectrometry of furostanol saponins combined with electrospray ionization in positive and negative ion modes

“…However, this elimination of 144 Da is disadvantageous for provision of sequence and some linkage information on the sugar moieties. Ion trap mass spectrometers provide MS/MS information in a different collision energy regime, and have been widely used in qualitative structural analyses and especially have an advantage in analyses of saponins using positive and negative ion electrospray ionization 12–19…”

Analysis of macrolide antibiotics, using liquid chromatography‐mass spectrometry, in food, biological and environmental matrices

“…LC/ QIT quantitative and qualitative applications for the determination of macrolides are summarized in Tables 2-4. The unique MS/MS and MS n capabilities of a QIT mass spectrometer have advanced its implementation to characterize and study fragmentation patterns of macrolides such as azithromycin (Debremaeker et al, 2003), josamycin propionate (Govaerts et al, 2004), clarithromycin (Leonard et al, 2006), dirithromycin (Diana et al, 2006), and erythromycin (Govaerts et al, 2000;Chitneni et al, 2004;Deubel et al, 2006), and to investigate their impurities ( Table 3). The QIT MS/MS and MS n experiments provided structurally rich spectra of the available macrolide reference standards and of unknown impurities.…”