We present an RP-HPLC method for the determination of the octanol-water distribution coefficients at pH 7.4, as log values, for neutral and basic drugs, which combines ease of operation with high accuracy. The method is shown to work for a training set of 90 molecules comprised largely of drugs, and it was also applied to a test set of 10 proprietary compounds. This work expands the applicability of the method presented in our earlier report, for the determination of logP(oct) for neutral compounds (J. Med. Chem. 2000, 43, 2922-2928), and it offers the same general features but widens the scope. Generally, the method (i) is compound sparing (< or =1 mL of a 50-100 microg/mL solution needed), (ii) is insensitive to concentration and phase ratio effects observed in some shake-flask determinations, (iii) is amenable to rapid determinations (< or = 20 min on average), (iv) is insensitive to impurities, (v) possesses a wide lipophilicity range (>7 log units), and (vi) offers a good accuracy, (vii) an excellent reproducibility, (viii) and an excellent potential for automation. 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 ElogD(oct).