Prediction of human serum albumin-drug binding affinity without albumin |
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Authors: | Toshihiko Hanai A KosekiR Yoshikawa M UenoT Kinoshita H Homma |
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Affiliation: | a Health Research Foundation, Institut Pasteur 5F, Sakyo-ku, Kyoto 606, Japan b School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo, Japan |
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Abstract: | A new liquid chromatographic system was developed to measure protein-drug binding affinity indirectly without albumin and was evaluated using log nK values of drugs measured by a modified Hummel-Dreyer method using purified human serum albumin. The retention factors of acidic and basic drugs were measured by reversed-phase and ion-exchange liquid chromatography in sodium phosphate buffer, pH 7.40, containing 50 vol.% methanol at 37 °C. The bonded phases were pentyl, guanidino and carboxyl phases. The combined retention factors were correlated with the log nK values measured by a modified Hummel-Dreyer method because glycosylation of human serum albumin did not significantly affect log nK value. The correlation coefficients were 0.949 (n=7) for acidic drugs and 0.978 (n=5) for basic drugs. The log nK values of 26 acidic and 18 basic drugs were predicted from their retention factors measured by reversed-phase and ion-exchange liquid chromatography. |
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Keywords: | Prediction of binding affinity Human serum Albumin Drugs Chromatography |
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