Study the effect of a pseudo-carrier on pharmacokinetics of 9-fluoropropyl-(+)-dihydrotetrabenazine in rat plasma by ultra-performance liquid chromatography-tandem mass spectrometry

To evaluate the effect of a pseudo-carrier (9-hydroxypropyl-(+)-dihydrotetrabenazine, AV-149) on pharmacokinetics of 9-fluoropropyl-(+)-dihydrotetrabenazine (AV-133), an ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed and validated for the determination of AV-133 and AV-149 in rat plasma. AV-133 and AV-149 were extracted from plasma following protein precipitation. The chromatographic analysis was performed on an ACQUITY UPLC BEH (TM) C-18 column (50 mm x 2.1 mm x 1.7 mu m) by a gradient elution. The mass spectrometer was operated in positive mode using electrospray ionization. The analytes were measured using the multiple reaction-monitoring mode (MRM). An external calibration was used, and the calibration curves were linear in the range of 1.00-800 ng/mL for AV-133 and AV-149. The accuracy ranged from 90.8% to 113.2% and the precision ranged from 2.7% to 9.9% for each analyte. The effect of a pseudo-carrier on pharmacokinetics of AV-133 was studied using the presented method. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.