| The enantiomeric separation of chiral drugs plays an important role at present scientific fields. As the basis of chiral drug development, it is an important task to establish a simple and effective chiral separation analysis method in the field of pharmaceutical analysis. Two enantiomers of chiral drugs usually possess different pharmacokinetic action. It’s of great significance to establish this method for monitoring the biological activities and stereoselectivity of the enantiomers.In this paper, high performance liquid chromatography method using chiral stationary phases has been developed for the separation of Ofloxacin and Flumequine enantiomers; The stereoselective pharmacokinetics and the chiral inversion of Ofloxacin and Flumequine in Red porgy fish plasma have also been researched.1. Study on the enantiomeric separation of OfloxacinA High performance liquid chromatography method using the Chiralcel OD-H chiral column (4.6mmx250mm,5.0μm, Daicel) for the chiral separation and determination of ofloxacin enantiomers was developed. The Optimized chromatographic condition were hexane-ethanol (60:40,v/v) as the mobile phase with a flow rate of0.6ml/min and detection at the wavelength of294nm, the column temperature was set at25℃. The resolution of ofloxacin enantiomers was1.69under the chromatographic conditions. The LOD of S-(-)-OFLX and R-(+)-OFLX were0.02μg/g and0.03μg/g, the LOQ of S-(-)-OFLX and R-(+)-OFLX were0.04μg/g and0.05μg/g, respectively. The average recovery of S-(-) OFLX was83.46%, the RSD of intra-day and inter-day precisions were0.34%and0.44%respectively. The average recovery of R-(+)-OFLX was87.32%, the RSD of intra-day and inter-day precisions were0.46%and0.69%respectively2. Studies on the stereoselective pharmacokinetics of ofloxacin in Red porgy fishA Chiral Stationary Phase method to determine the enantiomers of Ofloxacin in Red porgy fish plasma has been researched. According to the result, Pharmacokinetic parameters of S-(-)-OFLX and R-(+)-OFLX ater an oral administration of20mg/kg of racemic OFLX to Red porgy fish were shown as follows, tl/2were11.6h and12.3h; Ke were0.42and0.64; Tpeak were6h; Cmax were7.33mg/L and8.73mg/L; AUC were16.28Mg/L-h and20.50Mg/L-h. The plasma concentration for R-(+)-OFLX were higher than S-(-)-OFLX in Red porgy fish’s plasma all the time. The mean Cmax and AUC value for S-(-)-OFLX were0.8and0.7time of those of R-(+)-OFLX, respectively. In a word, the pharmacokinetics of ofloxacin in Red porgy fish was stereoselective.And through detecting the concentration of S-(-)-OFLX in Red porgy fish, it was confirmed that the chiral inversion of ofloxacin could not happen in Red porgy fish.3. Study on the enantiomeric separation of FlumequineA High performance liquid chromatography method using the Chiralcel OD-H chiral column (4.6mm×250mm,5.0μm, Daicel) for the chiral separation and determination of Flumequine enantiomers was developed. The Optimized chromatographic condition were100%ethanol as the mobile phase with a flow rate of0.5ml/min and detection at the wavelength of254nm, the column temperature was set at20℃. The LOD of S-(-)-FMQ and R-(+)-FMQ were0.05μg/g and0.04μg/g, the LOQ of S-(-)-FMQ and R-(+)-FMQ were0.08μg/g and0.07μg/g, respectively. The average recovery of S-(-)OFLX was85.33%, the RSD of intra-day and inter-day precisions were0.45%and0.51%respectively. The average recovery of R-(+)-FMQ was83.28%, the RSD of intra-day and inter-day precisions were0.54%and0.47%respectively4. Studies on the stereoselective pharmacokinetics of Flumequine in Red porgy fishA Chiral Stationary Phase method to determine the enantiomers of Flumequine in Red porgy fish plasma has been researched. The stereoselective pharmacokinetics and the chiral inversion have been researched of Flumequine enantiomer afterwards a single oral administration at a dose of20mg/kg to Red porgy fish. According to the result, Pharmacokineticparameters of S-(-)-FMQ andR-(+)-FMQ ater an oral administration of20mg/kg of racemic FMQ to Red porgy fish were shown as follows, t1/2were12.4h and11.2h; Ke were0.48and0.62; Tmax were8h; Cmax were7.64mg/L and3.39mg/L; AUC were42.26Mg/L-h and18.68Mg/L-h. The plasma levels for S-(-)-FMQ were much higher than that of R-(+)-FMQ in Red porgy fish. The mean Cmax and AUC value for S-(-)-FMQ were2.25and2.26time of those of R-(+)-FMQ, respectively. In a word, the pharmacokinetics of Flumequine in Red porgy fish was stereoselective.And through monitoring the concentration of S-(-)-FMQ in Red porgy fish, it was confirmed that that the chiral inversion of Flumequine could not happen in Red porgy fish. |
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