Abstract：
:We present an RP-HPLC method, for the determination of logPoct values for neutral drugs, which combines ease of operation with high accuracy and which has been shown to work for a set of 36 molecules comprised largely of drugs. The general features of the method are as follows: (i) compound sparing (< or = 1 mL of a 30-50 microg/mL solution needed), (ii) rapid determinations (20 min on average), (iii) low sensitivity to impurities, (iv) wide lipophilicity range (6 logPoct units), (v) good accuracy, (vi) excellent reproducibility. A linear free energy relationship (LFER) analysis, based on solvation parameters, shows that the method encodes the same information obtained from a shake-flask logPoct determination. To the best of our knowledge a similar performance, on a set of noncongeneric drugs, has not been previously reported. We refer to the value generated via this method as ElogPoct.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Lombardo F,Shalaeva MY,Tupper KA,Gao F,Abraham MHdoi
10.1021/jm0000822keywords:
subject
Has Abstractpub_date
2000-07-27 00:00:00pages
2922-8issue
15eissn
0022-2623issn
1520-4804pii
jm0000822journal_volume
43pub_type
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