Mass spectrometry in the quantitative analysis of therapeutic intracellular nucleotide analogs

Mass Spectrometry Reviews
Robert S JansenJos H Beijnen

Abstract

Nucleoside analogs are widely used in anti-cancer, anti-(retro)viral, and immunosuppressive therapy. Nucleosides are prodrugs that require intracellular activation to mono-, di-, and finally triphosphates. Monitoring of these intracellular nucleotides is important to understand their pharmacology. The relatively involatile salts and ion-pairing agents traditionally used for the separation of these ionic analytes limit the applicability of mass spectrometry (MS) for detection. Both indirect and direct methods have been developed to circumvent this apparent incompatibility. Indirect methods consist of de-phosphorylation of the nucleotides into nucleosides before the actual analysis. Various direct approaches have been developed, ranging from the use of relatively volatile or very low levels of regular ion-pairing agents, hydrophilic interaction chromatography (HILIC), weak anion-exchange, or porous graphitic carbon columns to capillary electrophoresis and matrix-assisted light desorption--time of flight (MALDI-TOF) MS. In this review we present an overview of the publications describing the quantitative analysis of therapeutic intracellular nucleotide analogs using MS. The focus is on the different approaches for their direct ana...Continue Reading

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Citations

Aug 9, 2011·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Michael R L Stratford, Lisa K Folkes
Jan 24, 2020·Clinical Pharmacology in Drug Development·M Van NulandJ H Beijnen
Jan 4, 2020·Analytical and Bioanalytical Chemistry·Fan PuR Graham Cooks
Mar 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chih-Hao LinI-Chung Lu

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