Claims
- 1. A method of determining ElogPoct for chemical compounds which comprises:a) Introducing said chemical compounds seriatim to the column of a reverse phase high performance liquid chromatograph; said column being an embedded amide functional group column; or a C-18 bonded column with low silanol activity; and b) Eluting said compounds with a mobile phase containing MOPS buffer and a methanol/octanol mixture in which the proportions of said methanol/octanol mixture to said buffer are from 70 to 15% v/v; and with flow rates between 0.5 and 2 ml/mm and with the proviso that said mobile phase does not contain an aliphatic amine; and c) Measuring the retention time required to elute each sample from said column; and d) Calculating ElogPoct from the retention time of each sample using equation 3: logPoct=1.1021(±0.0291)logkw+0.1344(±0.0653) (Eq. 3).
- 2. The method of claim 1 wherein each of steps a) through d) is preformed by robotic means under the control of a programmed computer.
- 3. The method of claim 1 wherein said column is a C-18 bonded column with low silanol activity.
- 4. A method of determining ElogPoct for chemical compounds which comprises:a) Introducing said chemical compounds seriatim to the column of a reverse phase high performance liquid chromatograph; said column being an embedded amide functional group column; or a C-18 bonded column with low silanol activity; and b) Eluting said compounds with a mobile phase containing MOPS buffer and a methanol/octanol mixture in which the proportions of said methanol/octanol mixture to said buffer are from 70 to 15% v/v; and with flow rates between 0.5 and 2 ml/min and with the proviso that said mobile phase does not contain an aliphatic amine; and c) Measuring the retention time required to elute each sample from said column; and d) Calculation ElogPoct from the retention time of each sample using equation 3: logPoct=1.1021(±0.0291)logk′w+0.1344(±0.00653) (Eq.3), wherein said compounds for which ElogP.sub.oct is to be determined are divided into groups according to calculated lipophilicity based on chemical structure and; ElogP.sub.oct is determined for all samples in a first group and; said column is equilibrated to the conditions for a second group.
- 5. The method of claim 4 wherein said compounds are divided into three groups wherein the first group has a calculated logPoct range of 0.5 to 1; the second group has a calculated logPoct range of 1 to 3 and the third group has a calculated logPoct of greater than 3.
- 6. The method of claim 5 wherein the flow rate and % of methanol are adjusted to the conditions shown below for each logPoct range:logPoct RangeFlow rate (mL/min)% MeOH−0.5 to 10.515, 20, or 251-3140, 45, or 50>3260, 65, or 70
- 7. The method of claim 6 wherein said logPoct values are calculated by a programmed computer and samples within a defined logPoct range are introduced seriatim into said column by robotic means under control of a programmed computer and calculating and recording each ElogPoct from the retention time of each sample by equation 3.
- 8. A method of determining ElogPoct for chemical compounds which comprises:a) Introducing said chemical compounds seriatim to the column of a reverse phase high performance liquid chromatograph; said column being an embedded amide functional group column; or a C-18 bonded column with low silanol activity; and b) Eluting said compounds with a mobile phase containing MOPS buffer and a methanol/octanol mixture in which the proportions of said methanol/octanol mixture to said buffer are from 70 to 15% v/v; and with flow rates between 0.5 and 2 ml/mm and with the proviso that said mobile phase does not contain an aliphatic amine; and c) Measuring the retention time required to elute each sample from said column; and d) Calculating ElogPoct from the retention time of each sample using equation 3: logPoct=1.1021(±0.0291)logkw+0.1344(±0.0653) (Eq. 3), wherein said column is an embedded amide functional group column.
CROSS-REFERENCE TO RELATED APPLICATION
This application claims priority of U.S. provisional application No. 60/182,353, filed Feb. 14, 2000.
Non-Patent Literature Citations (3)
Entry |
Minick et al, J. Med. Chem., vol. 31 (1988) pp. 1923-1933.* |
Britto et al, Chromatographia, vo. 53, No. 1/2 (2001), pp. 11-16.* |
Pagliara et al, J. Liq. Chromatography, vol. 18 (1995), pp. 1721-1745. |
Provisional Applications (1)
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Number |
Date |
Country |
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60/182353 |
Feb 2000 |
US |