Fast-atom bombardment mass spectrometry of netilmicin and its 6′-N-aminoacyl derivatives

Abstract

Netilmicin is a potent, broad-spectrum, aminocyclitol antibiotic prepared by chemical modification of the naturally occurring aminoglycoside sisomicin. It is markedly less nephrotoxic and ototoxic than sisomicin and is in clinical use in a number of countries. Electron ionization (EI) mass spectrometry has been applied to sisomicin. However, EI is characterized by a low abundance (1%) of the molecular ion which is essential for correct identification. It has been reported that field desorption and californium-252 plasma desorption in the positive-ion mode can produce suitable [M + H] or [M + Na] ions from unsaturated aminoglycosides. We have recently published the fact that substitution of netilmicin at the 6′-N position by L-alanine causes a 2-fold reduction of its toxicity, due to the orientation adopted by the antibiotic interacting with phosphatidylinositol. The aim of this work is to study the fragmentation pathways of netilmicin (1) and its 6′-N-aminoacyl derivatives 2–6 (Table 1) by fast-atom bombardment mass spectrometry (FAB-MS) in combination with tandem mass spectrometry (MS/MS). It has been clearly demonstrated that FAB-MS/MS is an effective method for analysis of these non-volatile and thermally labile compounds.