Journal
JOURNAL OF CHROMATOGRAPHY A
Volume 1175, Issue 1, Pages 16-23Publisher
ELSEVIER
DOI: 10.1016/j.chroma.2007.09.093
Keywords
accuracy; automated; log P-o/w; gradient-flow; liquid-liquid partition chromatography; pharmaceuticals
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There is a continuing need for a method which can measure log P-octanol/water accurately and precisely. Liquid-liquid partition chromatography is ideally suited for this as the retention time is a direct function of the partition or distribution coefficient. However, the range of measurements using isocratic-flow conditions is limited by the log-linear relation between run time and log P-o/w. The use of gradient-flow programming and short columns gives a more versatile procedure, so that appropriate data points can be collected at both the low and high ends of the chromatographic run, corresponding to log P-o/w values between 1 and 4. At the same time the precision, accuracy and versatility of the method are kept. This study is a validation of the procedure and measures the log P-o/w on 23 representative pharmaceuticals, comprising a mixed set of neutral compounds. The linear plot fitting micropartition log P-o/w and those found in literature shows a slope close to unity and a residuum close to zero. This indicates that gradient-flow micropartition chromatography is ruled by partitioning between octanol and the aqueous phase. (c) 2007 Elsevier B.V. All rights reserved.
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