HIGH PERFORMANCE LIQUID CHROMATOGRAPHSC ASSAY AND PHARMACOKINETIC INVESTIGATION OF KETOCONAZOLE IN HEALTHY SUBJECTS
- VernacularTitle:高效液相色谱法测定酮康唑血浓度及正常人药代动力学研究
- Author:
Gaolin LIU
- Publication Type:Journal Article
- Keywords:
ketoconazole;
high-performance liquid chromatography;
pharmacokinetics
- From:
Academic Journal of Second Military Medical University
1981;0(04):-
- CountryChina
- Language:Chinese
-
Abstract:
A reversed-phase high performance liquid chromatography (HPLC) method for the rapid determination of ketoconazole in human plasma is described.The column was 15 cm?4.0 mm ID stainless steel packed with HITACHI GEL 3056 (ODS). A guard column (PRECOLUMN) 5 cm?5.0 mm packed with YWG-C18H37(40?m) was attached to the primary column.The mobile phase consisted of methanol:0.02 mol/L phosphate buffer (pH 7.61)(72:28, vol/vol) and the flow rate was 0.7 ml/ min.Chromatography was performed wih variable UV monitor at 217 nm.N-(p-bromo-phenyl)-2-amino-4. 5-dihydrothiazole was used as an internal standard.The retention time for hetoconazole and internal standard were 11 min 18 s and 7 mm 13 s, respectively. The detection limit was 10 ng.The average recoveries (2?g/ml) of within-day and between-day were 96.80?3 . 13% (CV- 3.23% ) and 92.68 ?2.09% (CV = 2.26), respectively.The pharmacokinetics of ketoconazole was studied by the above HPLC method after a single oral dose of 400 mg in six healthy subjects .The drug concentration-time curve was a two compartment open model with an equation C = 23 .3574e-0.2055t + 9. 5528e-0.1131t - 32.9102e-0.4229tThe pharmacokinetic parameters of ketoconazole obtained were as follows(mean value) : T1/2?=6.2060h, Cmax= 7. 6553?g/ml,Vd= 0.8375 L/Kg,CL = 0.0932 L/h/Kg.The results show that the HPLC method is rapid, sensitive, highly specific and accurate, and is suitable for the studies of pharmacokinetics and clinical monitoring of ketoconazole concentrations in human plasma.
