| The first object of this study is to develop a sensitive, specific, reproducible and simple LC-ESI-MS method for the determination of tiopronin concentration in human plasma. A HPLC/MS method for determination of tiopronin in human plasma was described for the studies of its relative bioavailability. Vitamin C and dithiothreitol were used to stabilify tiopronin in the treatment of plasma samples. The analytes were separated at 25℃with a flow rate of 1.0mL/min on Agilent SB-Aq column packed with 5μm C18 silica, using the acidic aqueous solution (pH4.5~4.7)including 0.5mmol/L tris (hydroxymethyl) aminomethane (Tris) and methanol(95:5, v/v) as a mobile phase. The outlet of the colimn was split, and only 1/3 portion of the column effluent was delivered into ESI source. Mass spectra were operated in negative ion mode , selective ion monitors(SIM) were at m/z162.0 at 4~8min and 178.0 at 8~15min for tiopronin and cyclamate, respectively.Nitrogen used as desolvation gas which was at a flow rate of 10L/min and gas temperature was at 350℃. The nebulizer pressure was 40psi.Capillary voltages was 3500V. The fragmentor was 70V. The correlation coefficient of the calibration curve were better than 0.9995 in the range of 25.0~8155.0 ng/mL in human plasma. The relative recovery was 90.9-115%. The inter-day and intra-day accuracy was below 15%. The Limit of quantification was 25.0ng/mL( S/N 3:1 ). A relative simple, fast and sensitive HPLC-ESI-MS method for direct dermination of tiopronin in human plasma was proposed which was successfully applied to a Relative Bioavailability and bioequivalence study.A relative bioavailability and bioequivalence study is also gived. A randomized crossover design was performed in 20 healthy volunteers and cyclamate was chosed as a reference preparation. In the two study periods, a single 500 mg dose of either test tablets or reference tablets was administered to each volunteer. The main pharmacokinetic parameters were estimated and the results of test tablets were similar to those of reference tablets. The main pharmacokinetic parameters of the two formulations(T and C)were as follows:A Tmax of 5.30±1.84 h for T and of 5.80±2.46h for C;A Cmax of 5885.37±1550.22 ng/mL for T and of 5829.81±1949.30 ng/mL for C; A T1/2 of 21.46±11.09 h for T and of 22.51±9.19h for C. After its oral administration to human, the relative bioavailability of T was 97.56±14.53%. The results of statistical analysis showed T and R were bioequivalance preparations.In chapter two, an anionic cyclodextrin, several different CDs have been selected as chiral selective agent in the running electrolyte for the electrophoretic chiral separation of triazole drugs. The influence of several factors on the chiral separation of drug enantiomers was investigated. The enantiomeric resolution was mainly influenced by CD types, CD concentration and acidity of background electrolyte. The effects of the length of capillary, applied voltage and sample plug length on the enantiomeric resolution were also discussed. The results showed that five triazole drugs were mostly baseline separated by capillary electrophoresis. The method is simple, rapid, accurate, and has been proved to be a very powerful tool in chiral separations.
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