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Characterization of Synthetic and Natural Product Pharmaceuticals by Functional Group Analysis using Electrospray Ionization-Ion Trap Mass Spectrometry: A Mini-Review
Journal article   Peer reviewed

Characterization of Synthetic and Natural Product Pharmaceuticals by Functional Group Analysis using Electrospray Ionization-Ion Trap Mass Spectrometry: A Mini-Review

W Franklin Smyth, Stephen McClean, Carmelina F Massaro, Thomas J Smyth, Peter R Brooks and Virgina Rodriguez Robledo
Analytical Letters, Vol.48(17), pp.2661-2675
2015
url
https://doi.org/10.1080/00032719.2015.1045590View
Published Version

Abstract

cleavage from ring systems electrospray ionization ion trap mass spectrometry fragmentation functional group analysis natural product pharmaceuticals pharmaceutical characterization
This mini-review is concerned with the characterization of synthetic and natural product pharmaceuticals by functional group analysis using electrospray ionization-ion trap mass spectrometry. Studies of the electrospray ionization-ion trap mass spectrometry behavior of selected synthetic and natural product pharmaceuticals of low molecular mass have shown certain characteristic fragmentations in that functional groups are generally cleaved from ring systems either as even electron inorganic or organic molecules such as H2O, CO, CO2, alcohols, carboxylic acids, or as odd electron entities such as methoxy and methyl. This is particularly energetically favorable in the former case with the standard heat of formation at 298.15K of the ejected neutral molecule having a relatively high negative value. Fragmentation of pharmaceuticals involving the generation of odd electron entities such as the methyl radical is structure dependent and is to a large extent correlated with the stability of the newly formed free radical ions. The fragmentation data therefore provides useful information on the structure of these pharmaceuticals, their degradation products and metabolites. In some cases, the cleaving of functional groups may parallel the production of certain metabolites. In addition, electrospray ionization-ion trap mass spectrometry data on even and odd electron mass losses may be cross-referenced with data obtained from unknown analytes such as bioactive molecules isolated from natural sources which can then be of value in their structural characterization, assisting in the dereplication process. This mini-review on functional group analysis of selected pharmaceuticals by electrospray ionization-ion trap mass spectrometry provides examples of drug characterization following cleavage from ring systems of even electron molecules (e.g., hypnotic drugs, coumarins, phloroglucinols, and polyphenols) and odd electron entities (e.g., the alkaloid tetrandrine). Parallels between the cleaving of functional groups as even electron mass losses and the metabolic reactions of the macrocyclic antibiotic rifapentine are also discussed.

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