Abstract

European Journal of Mass Spectrometry
Volume 14 Issue 5, Pages 281–297 (2008)
doi: 10.1255/ejms.933

Collision induced dissociation studies of alkali metal adducts of tetracyclines and antiviral agents by electrospray ionization, hydrogen/deuterium exchange and multiple stage mass spectrometry

Amin Kamel^a,* and ^bBurnaby Munson
^aDepartment of Exploratory Medicinal Sciences, Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340. USA. E-mail: amin.m.kamel@pfizer.com
^bDepartment of Chemistry and Biochemistry, University of Delaware, Newark, Delaware, USA

The CID mass spectra were obtained for the X⁺-adducts (X = Na⁺ or Li⁺) of five tetracyclines, four pyrimidine and three purine derivatives and their fully D-exchanged species in which the labile hydrogens were replaced by deuterium by either gas phase or liquid phase exchange. The CID spectra were obtained for [M + Na]⁺ and [M + Li]⁺ and the exchanged analogs, [M(D) + Na]⁺ and [M(D) + Li]⁺, and compositions of product ions and mechanisms of decomposition were determined by comparison of the MSⁿ spectra of the undeuterated and deuterated species. Metal ions are bound to the base of purine and pyrimidine antiviral agents and dissociate primarily to give the metal complexes of the base [B + X]⁺. For vidarabine monophosphate, however, the metal ions are bound to the phosphate group, resulting in unique and characteristic cleavage reactions not observed in the uncomplexed system, and dissociate through the loss of phosphate and/or phosphate metal ion complex. The [B + X]⁺ of these antiviral agents are relatively stable and show no or little fragmentation compared to [B + H]⁺. The CID of [B + X]⁺ of guanine derivative occurs mainly through elimination of NH₃ and that of trifluoromethyl uracil dissociates primarily through the loss of HF. For tetracyclines, metal ions are bound to ring A at the tricarbonylmethyl group and dissociate initially by the loss of NH₃/ND₃ from [M_H + X]⁺ and [M_D + X]⁺. The CID spectra of [M + X]⁺ of tetracyclines are somewhat similar to those of [M + H]⁺. The dominant fragments from the metal complexes of these compounds are charge remote decompositions involving molecular rearrangements and the loss of small stable molecules. Additionally, tetracyclines and the antiviral agents show more selectivity towards Li+ ion than the corresponding complexes with Na⁺ or K⁺.

Keywords: H/D exchange, multiple stage MS, anti-viral agents, tetracyclines, alkali metal adducts, CID

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