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Octanol/water partitioning simulation by RP ‐ HPLC for structurally diverse acidic drugs: Comparison of three columns in the presence and absence of n ‐octanol as the mobile phase additive
Author(s) -
Giaginis Costas,
Theocharis Stamatios,
TsantiliKakoulidou Anna
Publication year - 2013
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.201300711
Subject(s) - lipophilicity , chemistry , octanol , partition coefficient , high performance liquid chromatography , chromatography , phase (matter) , ionization , aqueous solution , reversed phase chromatography , analytical chemistry (journal) , ion , stereochemistry , organic chemistry
The advantageous effect of n ‐octanol as a mobile phase additive for lipophilicity assessment of structurally diverse acidic drugs both in the neutral and ionized form was explored. Two RP C 18 columns, ABZ + and A quasil, were used for the determination of log k w indices, and the results were compared with those previously reported on a base‐deactivated silica column. At pH 2.5, the use of n ‐octanol‐saturated buffer as the mobile phase aqueous component led to high‐quality 1:1 correlation between log k w and log P for the ABZ + column, while inferior statistics were obtained for A quasil. At physiological pH, the correlations were significantly improved if strongly ionized acidic drugs were treated separately from weakly ionized ones. In the latter case, 1:1 correlations between log D 7.4 and log k w oct indices were obtained in the presence of 0.25% n ‐octanol. Concerning strongly ionized compounds, adequate correlations were established under the same conditions; however, slopes were significantly lower than unity, while large negative intercepts were obtained. According to the absolute difference (diff = log D 7.4 –log k w ) pattern, base‐deactivated silica showed a better performance than ABZ + , however, the latter seems more efficient for the lipophilicity assessment of highly lipophilic acidic compounds. Aquasil may be the column of choice if log D 7.4 <3 with the limitation, however, that very hydrophilic compounds cannot be measured.