Identification of adenine nucleotide-containing metabolites of bisphosphonate drugs using ion-pair liquid chromatography-electrospray mass spectrometry

S Auriola, Julie Clare Frith, Michael John Rogers, A Koivuniemi, J Monkkonen

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Abstract

Bisphosphonates are synthetic pyrophosphate analogues, which are used as therapeutic drugs for the treatment of metabolic bone disorders. Some of these bisphosphonates can be metabolised in cells into non-hydrolysable nucleotide analogues. In this paper, we describe an ion-pairing high-performance liquid chromatography method that is compatible with negative ion electrospray mass spectrometry for the separation of these metabolites. Tandem mass spectrometry and collision-induced dissociation (CID) were used for identification of the metabolites. The CID mass spectra of bisphosphonate-adenine nucleotide adducts are very informative, because major fragment ions are formed by cleavage of the bisphosphonate moiety from the conjugate. The method was used for detection of the nucleotide metabolites of clodronate, tiludronate and etidronate in extracts from mammalian cells after treatment with bisphosphonates. (C) 1997 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)187-195
Number of pages9
JournalJournal of Chromatography B: Biomedical Sciences and Applications
Volume704
Issue number1-2
DOIs
Publication statusPublished - 19 Dec 1997

Keywords

  • bisphosphonates
  • adenine nucleotides
  • clodronate
  • tiludronate
  • etidronate
  • mold dictyostelium-discoideum
  • performance
  • amebas

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