Liquid-phase microextraction of basic drugs--selection of extraction mode based on computer calculated solubility data.

The extractability of 58 different basic drugs by 3-phase liquid-phase microextraction (LPME) was studied. Extraction recoveries were correlated to solubility data and log D data calculated with a commercial computer program. The basic drugs were extracted from 1.5 mL water samples (pH 13) through approximately 15 microL of dodecyl acetate immobilized within the pores of a porous polypropylene hollow fibre (organic phase), and into 15 microL of 10 mM HCl (acceptor solution) present inside the lumen of the hollow fibre. Compounds with a calculated solubility below 1 mg/mL at pH 2 were poorly recovered and remained principally in the organic phase. For these drugs, 2-phase LPME may be used as an alternative technique, where the aqueous acceptor phase is replaced by an organic solvent. In the solubility range 1-5 mg/mL, most drugs were effectively extracted (recovery >30%), whereas drugs belonging to the solubility range 5-150 mg/mL were all extracted with recoveries above 30% by 3-phase LPME. The hydrophilic nature of most drugs with solubilities above 150 mg/mL prevented them from entering the organic phase, and only those with log D >1.8 were effectively recovered by 3-phase LPME. For drugs with log D < 1.8 (and solubility >150 mg/mL), carrier-mediated LPME was found to be the preferred technique, where an ion-pair reagent (octanoic acid) was added to the sample. In the case of carrier-mediated LPME, the volume of sample was decreased to 100 microL to facilitate rapid extractions. Based on the present work, the extractability of new compounds may easily be predicted to speed up method development. Extractions were also accomplished from plasma samples, where interactions between proteins and the drugs may reduce the extraction recovery. However, dilution of the plasma samples with water and adjustment of pH into the alkaline region effectively suppressed drug-protein interactions for most of the drugs studied.