Affiliation:
1. Department of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, P.R. China
Abstract
Abstract:
Guanfacine, an α2-adrenergic (α2A) agonist long indicated to treat hypertension, is now being used to treat attention deficit hyperactivity disorder (ADHD) in adolescents. A simple rapid high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method to detect and quantify guanfacine provides a basis for studying its bioequivalence and pharmacokinetics in human plasma. This assay involves quantitation of guanfacine using its stable isotope labeled internal standard (IS) guanfacine-13C-15N3, without impact of ion suppression in plasma matrix. Electrospray ionization (ESI) in positive mode and multiple reaction monitoring (MRM) were used for guanfacine and guanfacine-13C-15N3 at the transitions m/z 246.1→60.1 and m/z 250.0→159.1 respectively. The sample preparation is optimized in this method with an accurate and simple protein precipitation method employing methanol. Linearity was demonstrated over within the range of 0.0500-10.0 ng/mL for guanfacine in plasma with correlation coefficients greater than 0.99. The method showed excellent reproducibility, Aaccuracy (Relative Error) of the method ranged from -2.897.2% to 108.98.9% even at the the lower limit of quantification (LLOQ), and total precision, expressed as the coefficient of variation, was between 1.6% and 10.5%. The average recoveries of guanfacine at three spiked levels of 0.150, 1.00 and 7.50 ng/mL waswere 103.93%, 97.91% and 100.22%, respectively. The validated method was applied successfully to a bioequivalence study of a fixed-dose of extended-release guanfacine hydrochloride (GXR) tablet (Test formulation) and Intuniv® (Reference formulation) in Chinese healthy subjects, 42 subjects under fasting condition and 30 subjects under feeding condition. Pharmacokinetic parameters were calculated using DAS 3.2.8, and 90% confidence intervals (CIs) of AUC0-t, AUC0-∞ and Cmax for guanfacine were all within 80.00-125.00%, suggesting that the two formulations were bioequivalent in terms of rate and extent of absorption.
Funder
International Science and Technology Cooperation Project of Jiangsu Province
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmaceutical Science,Molecular Medicine,Biochemistry,Biophysics
Cited by
1 articles.
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