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Use of the bromine isotope ratio in HPLC-ICP-MS and HPLC-ESIMS analysis of a new drug in development

Reputable Mentor II
Reputable Mentor II
Cuyckens F, Balcaen LI, De Wolf K, De Samber B, Van Looveren C, Hurkmans R, Vanhaecke F.
Anal Bioanal Chem. 2008 Apr;390(7):1717-29.
A combination of inductively coupled plasma mass spectrometry (ICP-MS) and electrospray ionization mass spectrometry (ESI-MS) was deployed for the metabolite profiling and metabolite identification of a new antituberculosis compound (R207910, also known as TMC207) that is currently in drug development. R207910 contains one bromine atom, allowing the detection by ICP-MS. Fluctuations in the Br sensitivity caused by the HPLC gradient were counteracted by the use of species-unspecific isotope dilution. In order to evaluate the method developed, the results obtained were compared with those acquired via radioactivity detection. HPLC-ESI-MS was used for the structural identification of R207910 and its metabolites. The 79Br/81Br isotope ratio is also valuable in the search for metabolites in the complex background of endogenous compounds obtained using HPLC-ESI-MS analyses. Data-dependent scanning using isotope recognition with an ion trap mass spectrometer or processing of Q-Tof data provides HPLC-ICP-MS-like “bromatograms”. The combination of accurate mass measurements and the fragmentation behavior in the MS2 spectra obtained using the Q-Tof Ultima mass spectrometer or MSn spectra acquired using the LTQ-Orbitrap allowed structural characterization of the main metabolites of R207910 in methanolic dog and rat faeces extracts taken 0–24 h post-dose.
Global Preclinical Development, Johnson & Johnson Pharmaceutical R&D, Turnhoutseweg 30, 2340, Beerse, Belgium.
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‎10-15-2021 11:24 AM
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