A high-performance liquid chromatographic (HPLC) method utilizing hexane extraction and a normal bonded phase column (NH2-alkylamine) was developed to measure serum concentrations of amiodarone and its N-deethylated metabolite. A single analysis requires 8 min. The one-step extraction efficiencies of amiodarone and the internal standard are greater than 90%. The method is linear between 0.05 and 20.0 micrograms/ml. The average relative standard deviation of the slope of the standard curve is 4% and the single day coefficient of variation is 3.2%. The use of hexane extraction for sample cleanup and a bonded phase column for chromatography result in a sensitive and reproducible system well suited to laboratories monitoring serum concentrations of multiple drugs by HPLC. A preliminary study has shown the assay to be useful for the investigation of the pharmacokinetics of this agent.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/s0378-4347(00)84840-9 | DOI Listing |
Br J Clin Pharmacol
March 2000
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa and; Daiichi Pure Chemicals Co. Ltd, Ibaraki, Japan.
Aims: To predict the drug interactions of amiodarone and other drugs, the inhibitory effects and inactivation potential for human cytochrome P450 (CYP) enzymes by amiodarone and its N-dealkylated metabolite, desethylamiodarone were examined.
Methods: The inhibition or inactivation potency of amiodarone and desethylamiodarone for human CYP activities were investigated using microsomes from B-lymphoblastoid cell lines expressing CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. The in vivo drug interactions of amiodarone and desethylamiodarone were predicted in vitro using the 1+Iu/Ki values.
Drug Metab Dispos
March 1994
Sanofi Recherche, Metabolism and Pharmacokinetics Department, Montpellier, France.
Metabolism of amiodarone to its N-deethylated derivative was investigated on a bank of human hepatic microsomal fractions, two of them lacking the CYP2D6 isozyme. Michaelis-Menten constants for amiodarone N-deethylation were 0.33 +/- 0.
View Article and Find Full Text PDFA high-performance liquid chromatographic (HPLC) method utilizing hexane extraction and a normal bonded phase column (NH2-alkylamine) was developed to measure serum concentrations of amiodarone and its N-deethylated metabolite. A single analysis requires 8 min. The one-step extraction efficiencies of amiodarone and the internal standard are greater than 90%.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!