The Analysis Of Four Antidiabetic Drugs In Viro And Formulation By HPCE

As glycuresis frequently occurring,the antidiabetic drugs are widely used to control blood sugar levels.Therefore,it is important for antidiabetic drugs to quality control and pharmacokinetics study in vivo.A high performance capillary electrophoresis(HPCE)method was used to analyze four antidiabetic drugs in vivo and formulation.The main content of this research are shown as follows.In the first chapter,the contents,significances,characteristics and analysis methods of drug quality research and pharmaceutical analysis in vivo were introduced.At the same time,the research overview of antidiabetic drugs was introduced.In the second chapter,a high performance capillary electrophoresis(HPCE)method was established for simultaneous detection of metformin hydrochloride(MET),rosiglitazone hydrochloride(RLZ),repaglinide(RGN)and glimepiride(GLM).In this experiment,the four antidiabetic drugs were separated in 5 mmol/L disodium hydrogen phosphate(pH7)running buffer,using a 61 cm fused-silica capillary(50 ?m i.d.,effective length 50 cm)at the running voltage of 17 kv.The detection wavelength was 203 nm.This method was successfully applied to the content determination of antidiabetic drugs in six formulations and the contents of four antidiabetic drugs were more than 96.00%.This method provided excellent linearity,precision and accuracy.The relative standard deviation(RSD)of intra-day and inter-day was less than 0.99% and 1.97%,respectively,and the recoveries were 98.88%~102.50%.The four antidiabetic drugs could be completely separated within 7 min.This HPCE method was fast,accurate,sensitive,cost effective and reliable for the routine quality control of MET,RLZ,RGN,GLM in formulations.In the third chapter,a high-performance capillary(HPCE)and a high-performance liquid chromatography(HPLC)were established for determination the content of MET and GLM in the combined metformin hydrochloride and glimepiride tablet(MHGT),and the data results from two methods were compared.The results of HPCE method showed that the linearity range of MET and GLM was 12.5~3750 ?g/mL(n=8,R=0.9997)and 1~200 ?g/m L(n=7,R=0.9983),respectively.The RSD of intra-day and inter-day was less than 1.22% and 1.66%,respectively.The limits of detection(LOD)of MET and GLM both were 0.1 ?g/m L and the recoveries were 98.33%~100.61%.The percentage contents of MET and GLM in the three batches of compound tablets were more than 99.93% and 99.00%,respectively.The results of HPLC method showed that the linearity range of MET and GLM was 1~100 ?g/m L(n=8,R=0.9971)and 0.1~100 ?g/m L(n=10,R=0.9954),respectively.The RSD of intra-day and inter-day was less than 0.42% and 0.62%,respectively.The LOD of MET and GLM was 0.1 ?g/m L and 0.08 ?g/m L,respectively,and the recoveries were 98.05%~100.67%.The percentage contents of MET and GLM in the three batches of compound tablets were more than 99.07% and 98.50%,respectively.Although the precision and LOD of HPCE are poorer than HPLC,the potential advantages of HPCE method,such as high resolution,sensitive,convenient,environmental protection and cost effective,should be given taken into account.In the fourth chapter,the HPCE method was used for studying the pharmacokinetics of GLM and MET in rabbits.The separation was carried out using a fused-silica capillary(75 ?m × 61 cm,effective length 50 cm)and UV detection wavelength at 229 nm.The optimized conditions were 35 mmol/L,pH 7.5 Tris buffer and voltage of 17 kV at 25 °C.After oral administration of glimepiride tablet,metformin hydrochloride tablet and compound metformin hydrochloride and glimepiride tablet(MHGT),the plasma concentrations of MET and GLM within 24 h in rabbit were detected.The results showed that the Tmax of GLM in glimepiride tablet,MET in metformin hydrochloride tablet and MET in compound MHGT was 4,1 and 1.5 h,respectively,and the Cmax was 6.99,5.27 and 3.89 ?g/mL,respectively.The HPCE was specificity and convenience because the plasma samples could be detected after deproteinized with methanol.The linear range of GLM and MET in blood samples was 5~100 ?g/mL(n=7,R=0.9977)and 0.05~40 ?g/mL(n=8,R=0.9999),respectively.The RSD was less than 3.29% and the recoveries were 93.63%~108.16%.This HPCE method could provide a analysis method for the pharmacokinetic study of four antidiabetic drugs in vivo.