High‐Resolution Mass Spectrometry and Its Applications

With the exception of the 12C isotope of carbon which has a mass arbitrarily set equal to exactly 12 Da, all isotopes have unique nonintegral masses. The elemental composition of a sample can therefore often be inferred from an accurate measurement of the relative molecular mass of the sample. This requires that the mass resolving power (RP) of the instrument in use must be sufficiently high for the peak on which the mass measurement is based to be resolved from peaks arising from other components of closely similar mass. For samples of relative molecular mass below 500, an RP of 20 000 is often adequate, but for samples such as peptides and proteins an RP of several hundred thousand is often required. The modes of operation, strengths and weaknesses of the several different types of mass analyzer currently available for the production of mass spectra of sufficiently high resolution are reviewed. Particular emphasis is placed on the use of mass spectrometry in the detection and identification of samples of biological origin for which its high sensitivity and specificity of information provided are of great importance. This article concludes with a brief review of the uses of high-resolution mass spectrometry, in which the difficulties encountered in working with samples of very high relative molecular mass are discussed and an account is presented of the information to be gained from time-dependent studies of H/D interchange at high resolution.