Analysis of an adenine nucleotide-containing metabolite of clodronate using ion pair high-performance liquid chromatography-electrospray ionisation mass spectrometry

Clodronate belongs to the family of bisphosphonates, which are synthetic an alogues of pyrophosphate. Bisphosphonates are widely used in the treatment of metabolic bone diseases. Some bisphosphonates, including clodronate, can be metabolized in cells into non-hydrolysable nucleotide analogues. In thi s paper. we describe a new method for extraction and quantitation of the cl odronate metabolite in cell lysates by using ion-pairing HPLC method that i s compatible with negative ion electrospray ionization mass spectrometry (E SI-MS). The method was used for detection of the metabolite of clodronate i n extracts from RAW 264 macrophage cells after treatment with clodronate. ( C) 2000 Elsevier Science B.V. All rights reserved.