FUNDAMENTAL-STUDIES IN REVERSED-PHASE LIQUID SOLID EXTRACTION OF BASIC DRUGS .3. SAMPLE MATRIX EFFECTS

Using a set of 13 basic solutes (including a quarternary ammonium compound) with controlled pK(a), log P and plasma protein binding, the factors which influence the extraction of these compounds from plasma by reversed-phase liquid-solid extraction have been studied. Direct analysis of plasma, avoiding deproteination, etc., is possible providing the sample is applied to the cartridge under the appropriate conditions. These conditions are dictated by the degree of plasma protein binding and are controlled and predicted from the lipophilicity of the compound. Plasma samples containing lipophilic compounds (log D(pH 7.4)>2.03) require acidification and samples containing more polar compounds (log D(pH 7.4)<0.9) should be applied untreated. Failure to use the appropriate conditions can result in significant losses from the cartridge on application or washing. In the intermediate lipophilicity range the optimal application conditions cannot be predicted. The effect of various aqueous-organic wash solvents have been investigated, and it was found that the cationic but not the proteinaceous components of plasma also affect the extraction process. This phenomenon which is probably due to an attenuation of the secondary cation exchange mechanism, results in more facile elution than when compounds are applied in water.