Reduction of Chemical Formulas from the Isotopic Peak Distributions of High-Resolution Mass Spectra

Abstract

A method has been developed for the reduction of the chemical formulas of compounds in complex mixtures from the isotopic peak distributions of high-resolution mass spectra. The method is based on the principle that the observed isotopic peak distribution of a mixture of compounds is a linear combination of the isotopic peak distributions of the individual compounds in the mixture. All possible chemical formulas that meet specific criteria (e.g., type and number of atoms in structure, limits of unsaturation, etc.) are enumerated, and theoretical isotopic peak distributions are generated for each formula. The relative amount of each formula is obtained from the accurately measured isotopic peak distribution and the calculated isotopic peak distributions of all candidate formulas. The formulas of compounds in simple spectra, where peak components are fully resolved, are rapidly determined by direct comparison of the calculated and experimental isotopic peak distributions. The singular value decomposition linear algebra method is used to determine the contributions of compounds in complex spectra containing unresolved peak components. The principles of the approach and typical application examples are presented. The method is most useful for the characterization of complex spectra containing partially resolved peaks and structures with multiisotopic elements.

Efficient calculation of exact mass isotopic distributions

“…A number of methods [1][2][3][4][5][6][7][8][9] have been employed to elucidate the fine isotopic structure. The majority are polynomial based methods that rely on pruning to reduce the complexity to a more manageable size.…”

Efficient calculation of accurate masses of isotopic peaks

“…The method of reference [2] is extremely fast and generally produces results within a few millimass units [2,3]. Although semi-accurate masses are useful for many applications, in some cases being more accurate than experimental measurements of masses [3], for other applications accurate masses would be preferable.Accurate masses of isotopic peaks can be calculated by several methods. Polynomial-based methods work well for low and medium molecular weight compounds, but become computationally inefficient at high molecular weights.…”

“…Masses of the individual isotopic peaks are calculated at each convolution step as a probability weighted sum of the contributions to each peak [3]. This method is accurate, but computational efficiency is not optimal.…”

“…Kubinyi [1] and Rockwood and Van Orden [2] have described fast methods that also produce semi-accurate masses. The method of reference [2] is extremely fast and generally produces results within a few millimass units [2,3]. Although semi-accurate masses are useful for many applications, in some cases being more accurate than experimental measurements of masses [3], for other applications accurate masses would be preferable.…”

“…The method presented here is related to both the Kubinyi method [1] and the Roussis-Prouix method [3]. It is based loosely on Kubinyi's general approach of subdividing the calculation into a binary series of steps.…”