| Microdialydsis sampling combined with capillary electrophoresis was applied to study the pharmacokinetics of four commercial drugs. The temperature, microdialysis flow rate, components of the perfusion fluid and the buffer, injection time, separation voltage et al were optimized. All data were calculated using pharmacokinetic soft ware.The thesis consists of two parts:Part one: The research works about Pharmaceutical applications of capillary electrophoresis in recent years; Capillary electrophoresis as a versatile tool for the pharmacokinetic study; The research works in recent years about the application of microdialysis and capillary in pharmacokinetic were reviewed.Part two is research reports which is composed of 4 components as follows: I. In situ, in vivo, real time monitoring the concentration of cefazolin sodium in rabbit plasma by microdialysis sampling and capillary electrophoresis with UV detection; II. Pharmacokinetic study of trimebutine maleate in rabbit blood using in vivo microdialysis coupled to capillary electrophoresis; III. Determination of unbound metoprolol in rabbit blood by microdialysis and capillary electrophoresis; IV. Microdialysis coupled with capillary electrophoresis for continuous monitoring of free tramadol in rabbit blood.I. In situ, in vivo, real time monitoring the concentration of cefazolin sodium in rabbit plasma by microdialysis sampling and capillary electrophoresis with UV detectionIn vivo determining the concentrations of cefazolin sodium (CFZ) in rabbit plasma at different time after an iv dose by microdialysis sampling (MD) coupled with capillary electrophoresis (HPCE-UV) was established. The running buffer was 50 mmol/L borax buffer (pH 9.5), the running voltage was 20 kV, and the wave length was 214 nm. Under the optimized conditions, with ciprofloxacin as internal standard (IS), separation of CFZ from IS and other components in the dialysate was achieved within 15 min, the response of CFZ in plasma dialysate was linear over the range of 1-300 μg/mL, the detection limit was 0.3 μg/mL (3σ). Using 9 nL as the injection volume, the corresponding mass detection limit was 2.7×10-12 g. The recovery of microdialysis probe was 31.8% andRSD was 6.8% (n=3) at the perfusion rate of 3 μL/min. All data was analyzed by NDST pharmacokinetic software, the half-life for CFZ in rabbit was 24.5 min.Ⅱ. Pharmacokinetic study of trimebutine maleate in rabbit blood using in vivo microdialysis coupled to capillary electrophoresisIn vivo microdialysis was used together with capillary electrophoresis (CE) to monitor the concentration of trimebutine maleate (TM) in rabbit blood. Dialysis probe was perfused at 3 μL/min resulting in relative recovery of 26.6 ±3.1% (n=3). After a one step sample preparation the samples were injected directly into the capillary. TM was detected on-column using UV detector at 214 ran. Separation of TM from other components in the dialysate was achieved within 15 min. Evaluation was based on the relative collected peak height (TM/IS). The response for TM in the blood dialysate was linear over the range of 0.5-100 μg/mL. The detection limit of TM in the blood dialysate was 0.1 μg/mL (S/N=3). This method has been successfully applied to the pharmacokinetic study of trimebutine maleate in rabbit blood following oral administration of 200 mg/kg. It provides a fast and simple technique for the pharmacokinetic study of TM in vivo.Ⅲ. Determination of unbound metoprolol in rabbit blood by microdialysis and capillary electrophoresis: A pharmacokinetic studyA microdialysis method followed by a capillary electrophoresis procedure has been performed for the assay of unbound metoprolol in rabbit blood. A microdialysis probe was inserted into the ear vein for blood sampling. The electrophoresis conditions were: 47(40) cm × 50 μm silica capillary, 50 mmol/L acetate pH 4.0, 10 s hydrodynamic load, detection wavelength 214 nm, run voltage18 kV, temperature 25 ℃. In vitro recoveries of microdialysis probes were determination and capillary electrophoresis resolution and detection were validated for response linearity as well as intra- and inter-day variabilities. The method was then applied to pharmacokinetics profiling of metoprolol in the blood following oral administration of metoprolol (60 mg/kg) in rabbits. Pharmacokinetics were calculated from the corrected data for dialysate concentrations of metoprolol versus time. This study demonstrated the applicability of this continuous sampling method for pharmacokinetic study.Ⅳ. Microdialysis coupled with capillary electrophoresis for continuous monitoring of free tramadol in rabbit bloodThis report describes a pharmacokinetic study protein-free tramadol in rabbit blood... |
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