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RP-HPLC Method For Lipophilicity Measurement Of Compounds

Posted on:2010-01-28Degree:MasterType:Thesis
Country:ChinaCandidate:J LiuFull Text:PDF
GTID:2131330338987999Subject:Medicinal chemistry
Abstract/Summary:PDF Full Text Request
Objective: A set of 11 model solutes and drugs were selected to determine their extrapolated logkw of the retention factor logk by Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC)in two different stationary phases(XTerra RP 18,YMC- Pack ODS-A). Compared the correlations of extrapolation capacity factors logkw and the lipophilicity partition coefficients (logPoct) in two stationary phases. The previous experiments analyzed by a method based on linear solvation-energy relationships (LSERs) had already demonstrated that the retention mechanism of the compounds on the XTerra RP 18 stationary phase was similar to the mechanisms of the solutes'partition in octanol/water system. And the polar embedded ligands phase XTerra RP 18 phase was more suitable for the rapidly determining lipophilicity. On this basis, a set 35 compounds and drugs of various structures and properties (neutral, amphoteric, acid and basic compounds) were selected to determine their extrapolated logkw of the retention factor logk by the XTerra RP 18 stationary phase to explore the feasibility and range of determining method of the the XTerra RP 18 stationary phase.Method: XTerra RP 18 stationary phase was applied to determine the 35 compounds'logk and extrapolated to 100% H2O (phosphate buffer)logkw and established the linear regression equation of logkw and logPoct by the sas JMP6.0 to discuss the the feasibility and range of determining method of the the XTerra RP 18 stationary phase. Calculated the previous 11 compouds'logPpre by introduce the logkw into the linear regression equation and analyzed the logPpre and logPoct by SPSS.Results: The linear regression equation of logkw value and logPoct value of neutral, amphoteric, acid and basic compounds: logPoct =0.8964(±0.219)logkw+0.1805(±0.201) n=35, r2=0.9471, F=322The linear regression equation of logkw value and logPoct value of neutral and amphoteric compounds: logPoct=0.8151(±0.172)logkw +0.5466(±0.142) n=9, r2= 0.9832, F=410 The linear regression equation of logkw value and logPoct value of acid compounds: logPoct =1.0153(±0.340)logkw-0.0882(±0.352) n=10, r2=0.9634, F=211 The linear regression equation of logkw value and logPoct value of basic compounds: logPoct =0.9428(±0.376)logkw-0.0.0925(±0.0.360) n=16, r2=0.9706, F=462 Calculated the previous 11 compouds'logPpre value by introduce the logkw into the linear regression equation and analyzed the logPpre and logPoct by SPSS. There was no significant difference between logPoct value and logPpre value.Conclusion: The good correlation between the logkw and log Poct of the set of 35 neutral, amphoteric, acid and basic compounds indicated that the XTerra RP 18 stationary phase was appropriate to predict the log Poct of compounds of various structures and properties. And there was no significant difference between logPoct value and logPpre value.
Keywords/Search Tags:Lipophilicity, Partition coefficient, Retention factor, Reversed-Phase High-Performance Liquid Chromatography, XTerra RP 18, logPoct
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