Advances in structure elucidation of small molecules using mass spectrometry

Abstract

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules.Electronic supplementary materialThe online version of this article (doi:10.1007/s12566-010-0015-9) contains supplementary material, which is available to authorized users.

Illuminating the dark matter in metabolomics

“…The method has the potential to improve identification in metabolomics experiments, by expanding the search space outside of that available in spectral libraries. Dührkop et al (2) also point to the potential to search databases containing hypothetical simulated compounds, expanding the search space by an order of millions (10). Matching spectra in a metabolomics experiment to molecules whose structure has not yet been elucidated may well be in reach within the next few years.…”

Pharmacometabonomics and personalized medicine

“…It is used for determining the monoisotopic molecular mass of chemical entities and can also provide detailed information on molecular structure. 34 There are three main components to a mass spectrometer. Firstly, an ion source, which converts gas phase molecules into ions or, in the case of electrospray ionization, moves ions that exist in solution into the gas phase.…”

Principal Component Analysis with Linear and Quadratic Discriminant Analysis for Identification of Cancer Samples Based on Mass Spectrometry

“…2,3 This technique has been increasingly utilized in biomedical and clinical research, 4 since it can overcome many limitations of classical immunoassays 5,6 and supports the development of fast and less-invasive clinical procedures. [7][8][9] MS is usually coupled with chromatography such as liquid chromatography (LC-MS) and gas chromatography (GC-MS).…”