Simultaneous determination of OZ277, a synthetic 1,2,4-trioxolane antimalarial, and its polar metabolites in rat plasma using hydrophilic interaction chromatography

Ravi Kanth Bhamidipati, Julia Morizzi, Francis Chi Keung Chiu, David Shackleford, Susan Ann Charman

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OZ277 is a synthetic 1,2,4-trioxolane antimalarial currently being evaluated in clinical trials. Biotransformation of OZ277 in rats results in the generation of metabolites with large differences in polarity which complicates the development of a method for the simultaneous analysis of all species. A simple, sensitive and selective hydrophilic interaction liquid chromatography-mass spectroscopy (HILIC/MS) method for simultaneous determination of OZ277 and its major metabolites in rat plasma was developed and validated. The method involves protein precipitation with acetonitrile followed by separation on a Waters Atlantis (TM) HILIC Silica column using gradient elution. The analytes were monitored using a positive electrospray ionization interface in selected ion monitoring mode. The calibration range for all of the analytes was 5-10,000 ng/mL and the lower limit of quantitation was 5 ng/mL using a 50 i??m rat plasma sample. The inter- and intra-day accuracy and precision was within 12 . The recovery of all analytes from rat plasma over a wide concentration range was 90 or greater. The method has been successfully used for quantifying OZ277 and its metabolites in plasma following intravenous administration to rats.
Original languageEnglish
Pages (from-to)2989 - 2995
Number of pages7
JournalJournal of Chromatography B
Issue number27
Publication statusPublished - 2009

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