title: Study the effect of a pseudo-carrier on pharmacokinetics of 9-fluoropropyl-(+)-dihydrotetrabenazine in rat plasma by ultra-performance liquid chromatography-tandem mass spectrometry.
abstract: 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™ C₁₈ column (50 mm x 2.1 mm x 1.7 μm) 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.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.forename: Jinping
authors.initials: J
authors.lastname: Qiao
authors.forename: Wei
authors.initials: W
authors.lastname: Yin
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005462:Fluorine Radioisotopes / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics; D016018:Least-Squares Analysis; D008297:Male; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D005462:Fluorine Radioisotopes; C549477:florbenazine F 18; D013747:Tetrabenazine