Determination Of The Content And Related Substances Of Fumarate Quetiapine Extended-release Tablets And The Prediction Of Drug’s Retention Behavior By MELC

Objective1.A method for the determination of the content of fumarate quetiapine extended-release tablets and the related substances by microemulsion liquid chromatography was established.2.Using microemulsion liquid chromatography to analyte and Predict the molecular microstructure of new compounds and chromatographic retention behavior and distribution mechanism in chromatographic analysis.The prediction model of chromatographic retention behavior provides a basis for the screening of new compounds.Method and results1.A Odyssil C18 chromatographic column(4.6 mm×250 mm,5μm)was used,the mobile phase consistsed of 3.0%(w/w)Brij35-6.0%(w/w)n-butanol-0.8%(w/w)n-heptane-90.2%(w/w)water(pH=5.0),Thechromatographic column temperature was 30℃,the flow rate was 1 ml/min,Sample volume was 20μL and the UV detection wavelength was 254 nm.As a result,there are a linear relationship in the range of 40.04~160.16μg/mL and the equation was A=53482c+134712,R~2=0.9996(n=6);The RSD of precision is 1.1%,the detection limit is 0.01μg/mL and the quantitative limit is 0.03μg/mL.The average recovery rate is 99.5%(RSD=1.2%).This method is green,simple and accurate for the determination of the quality and related substances of fumarate quetiapine extended-release tablets.2.The use of 12 steroids as test drug,to investigate the correlation between logk and logP,were investigated in the effect of the mobile phase composition(surfactant,oil phase),pH and chromatographic columns,including the effect of oil phase to test drug peak width were studied.The results showed that when ethyl acetate as the oil phase,the the chromatographic peak of compounds was most symmetrical and peak broadening rate was smaller.The results also showed that the best chromatographic column was Venusil ASB C8(T)column.The best model of prediction of retention behavior was 6.0%(w/w)Brji35-6.6%(w/w)-butanol-0.8%(w/w)ethylacetate-86.6%(w/w)water (pH=6.7).The logk-logP regression equation was logk=0.3331logP-0.4439,R~2=0.9598,and has a good correlation.3.The use of the 27 drugs(basic,acidic and neutral drugs)as the test drug,to investigate the linear relationship between logk and logP/logD,were investigated in the effect of the mobile phase composition(surfactant,oil phase),pH and chromatographic columns.The results showed that the best mobile phase was 6.0%(w/w)Brji35-6.6%(w/w)n-butanol-0.8%(w/w)ethyl acetate-86.6%(w/w)water(pH3.7).The correlation coefficient R~2 of the logk-logP/logD regression equation of the C8,C18 chromatographic column and the monolithic column of were over 0.9.In order to further investigate the effects of physical and chemical parameters on the chromatographic retention behavior on different chromatographic columns,3 physical and chemical parameters of PSA,MR and alpha are used to establish a quantitative structure retention prediction model(QSRR model).The prediction model was verified by selecting 9 verifying drugs(basic,acidic and neutral drugs).The results show that the prediction models on the 3 chromatographic columns have good prediction ability.