DEVELOPMENT OF A GAS-CHROMATOGRAPHY MASS-SPECTROMETRY METHOD FOR THE ANALYSIS OF AMINOGLYCOSIDE ANTIBIOTICS USING EXPERIMENTAL-DESIGN FOR THE OPTIMIZATION OF THE DERIVATIZATION REACTIONS

A packed column GC-electron-capture detection method for the analysis of the aminoglycoside antibiotics kanamycin and gentamicin was adapted to capillary GC-MS. The analytes were derivatised using a two-step pr ocedure involving trimethylsilylation of the hydroxyl groups with trim ethylsilylimidazole and acylation of the amino groups with heptafluoro butyrylimidazole. Electron impact mass spectra of the resulting deriva tives of kanamycin A and gentamicins C-1, C-1a and C-2 are given and i nterpreted. The derivatisation procedure was optimised using experimen tal design. This chemometrical approach considers main effects as well as interactions of the influential parameters, thus conducting a more thorough investigation of the method than the common step-by-step app roach. Optimisation using fractional factorial and Box Behnken Designs produced a derivatisation method featuring better yield than previous ly published methods while in many cases requiring less reagents and s horter reaction times. (C) 1998 Elsevier Science B.V. All rights reser ved.