Determination of Antimalarial Compound, ARB-89 (7β-hydroxy-artemisinin carbamate) in Rat Serum by UPLC/MS/MS and its Application in Pharmacokinetics
Journal of Chromatography B
Among all the antimalarial agents, artemisinin and its semi synthetic family of analogs are the most potent antimalarials available for the treatment of Plasmodium falciparum infections. But these analogs have a few issues such as shorter half-lives and low oral bioavailability values. In order to overcome these inherent problems, novel artemisinin analogs were synthesized from 7β-hydroxy artemisinin by the Department of Medicinal Chemistry, University of Mississippi using a new synthesis mechanism. Out of all the 7β-hydroxy artemisinin analogs synthesized, 7β-hydroxy artemisinin carbamate (ARB-89) was chosen as a lead compound because of its high in vitro and in vivo activity. In this manuscript, a sensitive and rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS) method was developed and validated for the quantification of ARB-89 in rat serum. The analysis was carried out on an Acquity™ UPLC BEH C18column (1.7 μm, 2.1 mm × 50 mm) with a flow rate of 0.3 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer in positive electrospray ionization (ESI) mode. The selected mass-to-charge (m/z) ratio transitions used in the multiple reaction monitoring (MRM) for ARB-89 and artemisinin (internal standard) were m/z 778.4 > 253.4 and m/z 283.4 > 151.1 respectively. The calibration curve was linear from 1.00 ng/mL to 10.0 μg/mL (r2 = 0.999). A simple protein precipitation method was used for extraction. Moreover, the inter-day and intra-day precision values were found to be less than 15%. The recoveries of the method ranged from 94.0% to 96.7% at three concentrations. ARB-89 in rat serum was found to be stable at room temperature for 12 h. This method was successfully used to quantitate the novel antimalarial compound ARB-89 after intravenous and oral administration to rats.
Copyright © 2012, Elsevier
Pabbisetty, Deepthi; Illendula, Anuradha; Muraleedharan, K. M.; Chittiboyina, Amar G.; Williamson, John S.; Avery, Mitchell A.; and Avery, Bonnie A., "Determination of Antimalarial Compound, ARB-89 (7β-hydroxy-artemisinin carbamate) in Rat Serum by UPLC/MS/MS and its Application in Pharmacokinetics" (2012). Office for Research Publications and Presentations. 34.