ABSTRACT
The aim of this study is to establish an HPLC method for simultaneous determinations of mifepristone and its metabolites, mono-demethylated mifepristone, di-demethylated mifepristone and C-hydroxylated mifepristone in plasma and to evaluate the pharmacokinetic characteristics of mifepristone tablet. Twenty healthy female Chinese subjects were recruited and a series of blood samples were collected before and after 0.25, 0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 12.0, 24.0, 48.0, 72.0 and 96.0 hours administration by a single oral dose of 75 mg mifepristone tablet. Mifepristone and its three metabolites were extracted from plasma using ethyl acetate and determined by high performance liquid chromatography. The main pharmacokinetic parameters of mifepristone and its metabolites, including Cmax, tmax, MRT, t(1/2), V, CL, AUC(0-96 h) and AUC(0-infinity), were calculated by Drug and Statistical Software Version 2.0. The simple, accurate and stable method allows the sensitive determinations ofmifepristone and its metabolites in human plasma up to 4 days after oral administration of 75 mg mifepristone tablet and the clinical applications of their pharmacokinetic studies.
ABSTRACT
AIM: To establish a sensitive HPLC method for determining the concentrations of paeonol in human plasma and to evaluate its pharmacokinetic characteristics. METHODS: A single oral dose of 160 mg paeonol capsules was given to 24 Chinese healthy volunteers. Paeonol was separated on a XB-C18 column with tetrahydrofuran-methanol-water-phosphonic acid (6∶60∶34∶0.1, V∶V) as mobile phase. The plasma concentrations of paeonol were determined and its pharmacokinetic parameters were calculated and evaluated using DAS 2.0. RESULTS: The linear range of the paeonol was 10-500 ng/mL and the determination limit was 10 ng/mL. The main pharmacokinetic parameters, as Cmax, tmax, t1/2,AUC0-3, AUC0-∞ after a single dose of paeonol capsules were (116±46)ng/mL,(1.02±0.13) h,(1.03±0.35) h, (174±45) ng/mL, (217±56) ng/mL,respectively. CONCLUSION: The HPLC method for determining paeonol concentration in plasma is rapid, sensitive and suitable for pharmacokinetic studies.
ABSTRACT
AIM: To determine the concentration of nisoldipine in human plasma by HPLC-MS method and investigate the pharmacokinetics of sustained and immediate-release preparations. METHODS: A C 18 column was used to separate nisoldipine from plasma with the mobile phase of a mixture of methanol-water-acetic acid (7525 0.1) at a flow rate of 1.0 ml?min -1. MS: atmospheric pressure electronic spray ionization (AP-ESI) and ion mass spectral (m/z) of 411 were selected to quantify nisoldipine. Internal standard (IS): atmospheric pressure electronic spray ionization and m/z of 441 for nimodipine. RESULTS: The linear range of the standard curve of nisoldipine was 0.2- 50 ?g?L -1 and the determination limit was 0.15 ?g?L -1. The recovery rate was more than 70%, and intra-day relative standard deviation (RSD) and inter-day RSD were less than 10%. After being given a single dose of 10 mg nisoldipine sustained release tablet, sustained release capsule and normal tablet, the half life(t 1/2 /h) were 6.08? 1.48, 7.06? 1.80 and 3.70? 0.25, the time to peak concentration (T peak /h) were 5.4? 0.7, 5.8? 0.4 and 2.0? 0.2, the peak concentration (C max / ?g?L -1) were 3.43? 0.55, 3.71? 0.24 and 9.18? 3.78, the area under time- concentration curve (AUC 0-t / ?g?h -1?L -1) were 31.10? 5.00, 33.63? 7.16 and 32.72? 5.09. But after being given multiple doses of nisoldipine, C max/ ?g?L -1 were 5.20? 0.27, 3.91? 0.22 and 5.30? 1.04, C min / ?g?L -1 were 0.72? 0.10, 0.77? 0.07 and 0.53? 0.07, DF were 175.00%? 16.34%, 177.10%? 18.43% and 247.92%? 57.71% respectively. The bioavailability of sustained- release tablet and capsule were 96%?12% and 102%?9% respectively. CONCLUSION: The determination of concentration of nisoldipine in human plasma by HPLC-MS method is sensitive and accurate. It can be used for the investigation of the bioavailability and pharmacokinetic of nisoldipine.