title: 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.
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.
authors.affiliation: College of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Dai
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Wang
authors.forename: Suilou
authors.initials: S
authors.lastname: Wang
authors.forename: Xijing
authors.initials: X
authors.lastname: Chen
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D005260:Female; D016316:Guanfacine / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D016316:Guanfacine
keywords: LC-MS/MS; beagle dogs; guanfacine; pharmacokinetics