STRUCTURE DETERMINATION OF CYCLOSPORINES BY MASS-SPECTROMETRY

Contribution of the modern mass spectrometry to the structure determin ation of cyclic peptides is explained with compounds belonging to a ph armaceuticallly important group of cyclosporins. In addition to the de termination of molecular weight and elemental composition of molecule, also the presence of individual amino acids may be estimated. Their s equence can be derived from the daughter ion mass spectra of the proto nated molecule obtained in a tandem experiment. Comparison of the char acteristic fragmentation of immonium ions in the spectra of peptides a nd free amino acids makes possible to distinguish even isobaric amino acids one from another. Examples of use of the tandem mass spectrometr y in the analysis of mixtures are presented. Coupling of high-performa nce liquid chromatography and mass spectrometry utilizing fast-atom bo mbardment, electrospray, and atmospheric pressure chemical ionization, is discussed. The quantitative analysis of cyclosporins in biological samples using laser desorption or fast-ion bombardment with time-of-f light ion analysis surpasses immunologic assays in selectivity and fas t performance.