title: Study the pharmacokinetics of AV-45 in rat plasma and metabolism in liver microsomes by ultra-performance liquid chromatography with mass spectrometry.
abstract: An ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed and validated to determine AV-45 in rat plasma. After the addition of the internal standard benzophenone, plasma samples were pretreated by protein precipitation. Chromatographic separation was achieved on an Acquity UPLC BEH C₁₈ column (50 × 2.1 mm, 1.7 µm) by gradient elution at a flow rate of 0.4 mL/min. Detection of analytes and internal standard (IS) was done by tandem mass spectrometry, operating in positive-ion and multiple reaction monitoring mode. The method was fully validated for its sensitivity, selectivity, accuracy and precision, matrix effect and stability study. The calibration curve showed good linearity over the concentration range 2.00-1000 ng/mL for AV-45. Intra- and inter-day precisions were less than 7.6%, and accuracy ranged from 100.6 to 107.8%. There was no matrix effect. The validated method was successfully applied to a pharmacokinetic study of AV-45 in rats. Additionally, the metabolism of AV-45 in rat liver microsomes was also studied by ultra-performance liquid chromatography combined with time-of-flight mass spectrometry (UPLC/TOF-MS). With the help of chromatographic behavior and accurate mass measurements, the metabolites were characterized.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yin
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.forename: Jinping
authors.initials: J
authors.lastname: Qiao
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000814:Aniline Compounds / Q000097:blood* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005026:Ethylene Glycols / Q000097:blood* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D016014:Linear Models; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000814:Aniline Compounds; D005026:Ethylene Glycols; C545186:florbetapir