Micellar liquid chromatography with dodecyl dimethyl betaine as an in vitro method for prediction of protein-drug binding

With the accelerating development of new drugs, there is a high need for rapid and simple screening technologies. In this paper, a new in vitro method, dodecyl dimethyl betaine (BS-12) micellar liquid chromatography (MLC) was presented for prediction of protein-drug binding based on the similar property of BS-12 micelles to protein. The predictive possibility of this method was validated by comparing the retention factors of drugs (antidiabetic and antibacterial drugs) on C18 modified by different surfactants with those on the protein column. Through the investigation of the concentration and pH effect on the retention of the drugs in BS-12 MLC, quantitative retention-protein binding relationships were established according to the retention factors in 0.2 M BS-12 (pH 7.4) MLC and those on the protein column. According to the relationships established, the protein binding of seven drugs for psychiatric disorders, six potential drugs for antibiotics and four commercial antibiotics were predicted. The results were consistent with those on the BSA column very well. This indicated, BS-12 MLC was a simple, fast and reproducible method to predict protein-drug binding.