Pyrazine CH- and NH-acids. Antithrombotic activity and chromatographic behaviour.

1. A series of newly synthesized pyrazine CH- and NH-acids was subjected to analytical and pharmacological studies. 2. The compounds were chromatographed in HPLC systems employing three reversed-phase columns and methanol-buffer solvents of various composition at acidic, neutral and alkaline pH. 3. Chemometrical analysis by the principal component method allowed for ordering of the compounds on a plane determined by the first two principal component axes. 4. Pharmacological tests were done for representatives of the series of compounds. 5. An in vivo antithrombotic assay on mice proved diversified bioactivity within the group of agents. 6. Attempts were undertaken to relate chromatographic behaviour to antithrombotic activity. 7. Based on the results obtained, an approach was proposed to reduce the number of pharmacological tests in selecting the most promising agents.

High performance liquid chromatographic (HPLC) measures of hydrophobicity as determined by means of new HPLC columns.

Two new commercially available reversed phase high performance liquid chromatographic (HPLC) columns were tested from the view point of their usefulness for determination of hydrophobicity by means of partition chromatography. One column comprised a specially prepared hydrocarbon-bonded silica stationary phase material. The other column was packed with a polybutadiene-coated alumina (PBCA) phase. As reference served a regular commercial octadecylsilica (ODS) column. A series of test solutes were pyrazine CH- and NH-acids--the compounds which are able to take part in specific as well as in nonspecific intermolecular interactions. Unique properties of the new hydrocarbonaceous column manifested themselves in regular linear relationships between logarithms of capacity factors and volume percent of methanol in aqueous eluent. The main advantage of the PBCA column is a possibility of performing chromatography at alkaline pH. Both new columns are superior to regular ODS columns in respect of providing reliable chromatographic measures of hydrophobicity. It was observed that hydrophobicity parameters determined in individual HPLC systems are not highly intercorrelated and hence can reflect different structural features of solutes.

Chromatographic data for pharmacological classification of imidazol(in)e drugs.

A set of eighteen imidazol(in)e derivative drugs of various pharmacological activity were analysed under different high-performance liquid chromatographic (HPLC) conditions. Capacity factors were determined employing methanol-buffer eluents at seven volume ratios and at pH 10.9, 7.0 and 2.9. The use of an alkaline buffer was possible owing to the application of poly(butadiene)-coated alumina (PBCA) as the stationary phase. Two systems employing octadecylsilica (ODS) columns were applied, one operated at pH 7.0 and the other at pH 2.9. Capacity factors of the test solute drugs were determined in 21 chromatographic systems. All the data were subjected to chemometric analysis despite the fact that, except for the PBCA systems, only a limited range of linearity of the logarithm of capacity factor versus volume fraction of methanol in mobile phase was observed. The matrix of 21 x 18 capacity factors was statistically analysed by the principal component method. The first two principal components accounted for 80% of the variance in the capacity factors studied. The principal component object scores clearly separated the agents into groups in accordance with their pharmacological classification. It was concluded that diverse retention data can provide more information relevant to the bioactivity of solutes than just a one-dimensional hydrophobicity scale.