Title: Study on the Pharmacokinetics of Felodipine Sustained-release Tablets in Healthy Volunteers
Abstract: Objective: To establish a LC-MS/MS method for the determination of felodipine in human plasma to investigate the pharmacokinetics of felodipine sustained-release tablets in healthy volunteers.Methods: An Agilent HC C18column(150 mm×4.6 mm,5 μm) at a column temperature of 35 ℃ and a mobile phase consisting of methanol-0.05% formic acid(83 ∶17) and acetonitrile by linear gradient elution at a flow rate of 1 mL ·min-1 were used with an injection volume of 20 μL for LC.The positive ESI and MRM mode were used for triple quadrupole MS,in which the selected reaction monitoring ions were m/z 384.0→338.1 for felodipine and m/z 493.0→375.1 for cilnidipine as the internal standard.In the randomized,crossover study,twenty healthy male Chinese volunteers were divided into 2 groups and were given a single oral dose of 5 mg felodipine sustained-release tablets(test or reference formulation) after an overnight fast,followed by collecting cubital venous blood samples at different time points(0-72 h).Subsequently,the volunteers were given multiple oral doses(5 mg,qd,for 8 d)of test or reference formulation and the blood samples were collected in the same way on day 8.All the blood samples after plasma separation and extraction were determined by the established LC-MS/MS method and the pharmacokinetic parameters of felodipine were calculated by DAS2.0 software.Results: The established LC-MS/MS method was evaluated as follows:the calibration curve of felodipine in human plasma was linear in the range of 0.025-10 μg ·L-1,the precision,accuracy and recovery were good,and no significant matrix effect was found.The pharmacokinetics of felodipine sustained-release tablets were evaluated as follows: Cmax and AUC0-72,the main pharmacokinetic parameters,for test formulation were(1.29±0.49) mg ·L-1 and(21.2±5.0) mg ·h ·L-1 for single oral dose and(1.26±0.48) mg ·L-1 and(20.1±7.9) mg ·h ·L-1 for multiple oral doses(P0.05,vs reference formulation);Cmax,Tmax and AUC in steady state for multiple oral doses of both formulations showed no significant difference,compared with single oral dose.Conclusion: The LC-MS/MS method is proved to be specific,sensitive and accurate and it can meet the requirements for pharmacokinetic study of felodipine sustained-release tablets.There is no accumulation effect found after the multiple-dose administration of felodipine sustained-release tablets.
Publication Year: 2013
Publication Date: 2013-01-01
Language: en
Type: article
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