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

Franklin Smyth, Stephen McClean, C. Flavia Massaro, Thomas J. Smyth, Peter Brooks, Virginia Rodríguez Robledo

Research output: Contribution to journalArticle

Abstract

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 298.15 K 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.
LanguageEnglish
Pages2661-2675
JournalAnalytical Letters
Volume48
Issue number17
DOIs
Publication statusPublished - 2015

Fingerprint

Electrospray ionization
Biological Products
Functional groups
Mass spectrometry
Ions
Electrons
Pharmaceutical Preparations
rifapentine
Molecules
tetrandrine
Metabolites
Phloroglucinol
Coumarins
Molecular mass
Polyphenols
Carbon Monoxide
Carboxylic Acids
Hypnotics and Sedatives
Alkaloids
Free Radicals

Keywords

  • Cleavage from ring systems
  • Electrospray ionization ion trap mass spectrometry
  • Fragmentation
  • Functional group analysis
  • Natural product pharmaceuticals
  • Pharmaceutical characterization

Cite this

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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. / Smyth, Franklin; McClean, Stephen; Massaro, C. Flavia; Smyth, Thomas J.; Brooks, Peter; Robledo, Virginia Rodríguez.

In: Analytical Letters, Vol. 48, No. 17, 2015, p. 2661-2675.

Research output: Contribution to journalArticle

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KW - Cleavage from ring systems

KW - Electrospray ionization ion trap mass spectrometry

KW - Fragmentation

KW - Functional group analysis

KW - Natural product pharmaceuticals

KW - Pharmaceutical characterization

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M3 - Article

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JO - Analytical Letters

T2 - Analytical Letters

JF - Analytical Letters

SN - 0003-2719

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