Development and validation of a simple, sensitive and accurate LC‐MS/MS method for the determination of guanfacine, a selective α2A‐adrenergicreceptor agonist, in plasma and its application to a pharmacokinetic study. (8th July 2013)

• Record Type: Journal Article
• Authors: Li, Xiaonan; Li, Ning; Sun, Xiaolin; Yang, Wei; Dai, Yu; Xu, Jie; Zhang, Wei; Wang, Chunfeng; Wang, Suilou; Chen, Xijing
• Is Part Of: Biomedical chromatography. Volume 27:Number 12(2013:Dec.)
• Page Start: 1708
• Page End: 1713
• Publication Date: 2013-07-08
• Subjects: guanfacine -- LC‐MS/MS -- pharmacokinetics -- beagle dogs; Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.2983
• Languages: English
• ISSNs: 0269-3879

Abstract

ABSTRACT: A simple, practical, accurate and sensitive liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method was developed and fully validated for the quantitation of guanfacine in beagle dog plasma. After protein precipitation by acetonitrile, the analytes were separated on a C18 chromatographic column by methanol and water containing 0.1% (v/v) formic acid with a gradient elution. The subsequent detection utilized a mass spectrometry under positive ion mode with multiple reaction monitoring of guanfacine and enalaprilat (internal standard) at m / z 246.2 → 159.0 and m / z 349.2 → 205.9, respectively. Good linearity was obtained over the concentration range of 0.1–20 ng/mL for guanfacine in dog plasma and the lower limit of quantification of this method was 0.1 ng/mL. The intra‐ and inter‐day precisions were <10.8% relative standard deviation with an accuracy of 92.9–108.4%. The matrix effects ranged from 89.4 to 100.7% and extraction recoveries were >90%. Stability studies showed that both analytes were stable during sample preparation and analysis. The established method was successfully applied to an in vivo pharmacokinetic study in beagle dogs after a single oral dose of 4 mg guanfacine extended‐release tablets. Copyright © 2013 John Wiley & Sons, Ltd.