FUNDAMENTAL-STUDIES IN REVERSED-PHASE LIQUID SOLID EXTRACTION OF BASIC DRUGS .1. IONIC INTERACTIONS

Seven basic solutes with known and controlled pK(a) (7.93-9.5) and log P (0.23-6.63) values have been used as test probes to study the mechanisms involved in liquid-solid extraction with C2 and C18 bonded silica phases. A limited comparison has also been made with underivatized silica and CN phases. In addition to the reversed-phase mechanism, cation-exchange was shown to play a very significant role in the retention process. Various cations both organic and inorganic were assessed for their elution strength, and the ordering was similar to that for classical ion-exchange chromatography. Control of selectivity in the elution process can be achieved by varying the concentration of cation or methanol in the eluent. The C2 cartridge in combination with an aqueous ammonium acetate-methanol eluent proved to be the most versatile in that all compounds, irrespective of pK(a) or log P could be recovered in high yield. The optimal eluent in terms of selectivity with respect to related compounds could be predicted from the solute log P. Blocking of silanols by pre-conditioning the cartridges with cations prior to sample applications was also studied. The order of cation strengths although somewhat variable was similar to that established at the elution stage. To achieve quantitative elution with methanol or aqueous methanol solutions however, high concentrations of inorganic cations, equivalent to 1 ml of a 1 M solution were required to pre-condition a 100 mg cartridge.