Prediction on the chiral behaviors of drugs with amine moiety on the chiral cellobiohydrolase stationary phase using a partial least square method.
Quantitative Structure-Resolution Relationship (QSRR) using the Comparative Molecular Field Analysis (CoMFA) software was applied to predict the chromatographic behaviors of chiral drugs with an amine moiety on the chiral cellobiohydrolase (CBH) columns. As a result of the Quantitative CoMFA-Resolution Relationship study, using the partial least square method, prediction of the behavior of drugs with amine moiety upon chiral separation became possible from their three dimensional molecular structures. When a mixed mobile phase of 10 mM aqueous phosphate buffer (pH 7.0) - isopropanol (95:5) was employed, the best Quantitative CoMFA-Resolution Relationship, derived from the study, provided a cross-validated q2 = 0.933, a normal r2 = 0.995, while the best Quantitative CoMFA-Separation Factor Relationship, also derived from the study, yielded a cross-validated q2 = 0.939, a normal r2 = 0.991. When all of these results are considered, this QSRR-CoMFA analysis appears to be a very useful tool for the preliminary prediction on the chromatographic behaviors of drugs with an amine moiety inside chiral CBH columns.
Choi
Sun Ok
SO
Division of Biopharmaceutics, Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul 122-704, Korea.
Lee
Seok Ho
SH
Choo
Hea-Young Park
HY
D000588:Amines / Q000737:chemistry*; D043366:Cellulose 1,4-beta-Cellobiosidase / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005544:Forecasting; D007202:Indicators and Reagents; D016018:Least-Squares Analysis; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D013237:Stereoisomerism
D000588:Amines; D007202:Indicators and Reagents; D004364:Pharmaceutical Preparations; D043366:Cellulose 1,4-beta-Cellobiosidase