Journal
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
Volume 33, Issue 5, Pages 871-878Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0731-7085(03)00377-7
Keywords
microemulsion electrokinetic chromatography; immunosuppressive drugs; lipophilicity estimation; phosphatidylcholine; bile acids
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Retention (capacity) factors (k' values) of immunosuppressive drugs were determined in microemulsion electrokinetic chromatography (MEEKC) systems as a tool for the indirect estimation of partition coefficients (P-OW) between I-octanol and water. The microemulsions were based on phosphatidylcholine (PC) and bile acids (BAs) as biosurfactants and isopropyl myristate (IPM) as oil. Immunosuppressants were azathioprine (AZA), mycophenolate mofetil (MMF), tacrolimus (FK506) and cyclosporine A (CyA). Capacity factors of the analytes were determined from electrophoretic mobilities using an aqueous phosphate buffer (20 mM; pH 7.5) for all the systems. Retention was compared with that in the most commonly used microemulsion based on sodium dodecyl sulphate (SDS). log P-OW versus log k' calibration lines were constructed using reference compounds with known P-OW. In addition, data of log P-OW of the immunosuppressants were determined by partitioning between octanol and water, and were calculated by the aid of computer program. A different sequence of log P-OW for two analytes was found in the biosurfactant-based systems compared with the SDS-containing one. Excellent agreement was observed between the log P-OW values derived from the microemulsions containing deoxycholate compared with the data determined by partitioning between octanol and water. It was concluded that the retention factors in the systems with biosurfactants are good estimators for the partitioning in biological systems. (C) 2003 Elsevier B.V. All rights reserved.
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