Collisionally activated dissociations of aminocyclitol-aminoglycoside antibiotics and their application in the identification of a new compound in tobramycin samples

Abstract

Several aminocyclitol-aminoglycoside antibiotics have been studied by tandem mass spectrometry. Glycosidic bond cleavages were the major reactions in the low energy collisionally activated decomposition (CAD) of the protonated antibiotics. Only the glycoside residing on the C6-O of the 2-deoxystreptamine was observed to undergo significant decomposition at the C2-C3 and O-C1 bonds. The comprehension of the CAD of known aminoglycosides aided in the identification of an unknown impurity in tobramycin. The unknown compound was initially detected by reverse phase high-performance liquid chromatography following dinitrofluorobenzene derivatization of the amino groups. The molecular weight of the dinitrobenzene derivative measured by LC mass spectrometry (MS) led to the detection of two isomeric impurities in tobramycin by LC-MS using an amino column. Their CAD spectra were subsequently acquired by LC-MS/MS. One of the two compounds was determined to be a known compound, 6"-O-carbamyltobramycin with the carbamyl group substituted on the glycoside residing on the C6-O of 2-deoxystreptamine. The fragmentation pattern of the other compound was interpreted as that the unknown was also a carbamyltobramycin. The carbamyl group was, however, substituted on 2-deoxystreptamine. It was speculated that the carbamyl group was substituted at the C1 amino group. This compound, to our knowledge, has not been reported before.

Identification of Streptothricin Class Antibiotics in the Earlystage of Antibiotics Screening by Electrospray Ionization Mass Spectrometry

“…The difference of them was GL could produce (GL-NH 3 ) ion at m/z 316 at the same time, but GLLL almost lost water solely ( Table 1). The results indicated that the tendency of neutral loss was strongly influenced by the relative basicity of b -lysine chains, streptothricin D containing three b-lysine molecules making it more basic than streptothricin F. The similar phenomenon was also observed in the MS/MS research of some aminoglycoside antibiotics [18].…”

Impurity analysis of gentamicin bulk samples by improved liquid chromatography-ion trap mass spectrometry

“…142 Da for gentamicin C 2 , C 2a , C 2b ). Another typical fragment formed by the loss of 117 Da from the garosamine sugar has been reported [46][47][48]. The [M+H-117] + ion could be further fragmented to the ion at m/z 205 by the loss of ring A. Glycoside bond cleavage between ring A and B yields the ion m/z 322 (ring B and C, garamine) by the loss of ring A (e.g.…”

Identification of gentamicin impurities by liquid chromatography tandem mass spectrometry

“…Electrochemical [15][16][17] and evaporative light scattering detections [18,19] were used in the analysis of AG and gentamicin components with ion pairing chromatography. For detection of gentamicins also mass spectrometry can be used [19][20][21][22][23][26][27][28][29].…”

“…Glycoside bond cleavage was the main fragmentation mechanism and on the basis of relatively simple mass spectra, fragmentation pathway for two kanamycin A derivatives was proposed. Hu [28] proposed fragmentation mechanism for 10 AG antibiotics systematically investigated with CAD. The major components of gentamicin (C 1 , C 1a , C 2 , C 2a , C 2b ) were identified in bulk preparation of gentamicin sulphate [20].…”