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

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• 作者：Ravi K. Bhamidipati ; Julia Morizzi ; Francis C.K. Chiu ; David M. Shackleford ; Susan A. Charman
• 关键词：OZ277 ; RBx11160 ; 1 ; 2 ; 4-trioxolane ; Rat plasma ; HILIC/MS
• 刊名：Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences
• 出版年：2009
• 出版时间：1 October 2009
• 年：2009
• 卷：877
• 期：27
• 页码：2989-2995
• 全文大小：402 K

文摘

OZ277 is a synthetic 1,2,4-trioxolane antimalarial currently being evaluated in clinical trails. 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™ 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 μL 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.