E. Adams

Impurity Profiling of Dirithromycin by Liquid Chromatography Coupled to Electrospray Ionization Mass Spectrometry

The aim of this study was to characterize as much as possible the unknown peaks in the chromatogram obtained with a non-volatile LC-UV system, which was published earlier for the separation of dirithromycin and its related substances. For this purpose, each peak eluting from the non-volatile system was collected and transferred to a MS, after performing a desalting process. The desalting procedure uses a XTerra RP C18 column (250 mm x 4.6 mm, 5 µm) and two mobile phases consisting of a mixture of water / 0.1% (v/v) formic acid and a mixture of acetonitrile / 0.1% (v/v) formic acid, respectively. Mass spectral data were acquired on an LCQ ion trap mass spectrometer equipped with an electrospray ionization source (ESI), operating in the positive ion mode. In addition to the thirteen already known compounds, seven new compounds were elucidated. Five impurities showed modifications at the amino group of the desosamine molecule, one an alteration at position C-9 and one a modification at position C-13 of the macrolide ring.

9.3. Antibiotics

Publisher Summary The antibiotics are an important group of drugs, extensively used in human and veterinary therapy. Some are used on a very large scale to enhance animal growth. By definition antibiotic structures are of natural origin or are produced by synthesis as a structural analogue of a naturally-occurring antibiotic. The chemistry of antibiotics is so varied that a chemical classification is difficult. In this chapter, penicillins, cephalosporins, macrolides, tetracyclines, aminoglycosides, polypeptides and polyenes are discussed. As most antibiotics are obtained by fermentation or by semisynthesis from natural products, the total amount of impurities present might be rather large because related compounds, also formed during the fermentation process used to produce the antibiotics, often are difficult to remove. As the biosynthesis route followed during fermentation is not always fully understood, and the side reactions are not always known, the related substances often are not easy to identify.