TY - JOUR

T1 - Liquid-phase microextraction of basic drugs - Selection of extraction mode based on computer calculated solubility data

AU - Pedersen-Bjergaard, Stig

AU - Rasmussen, Knut Einar

AU - Brekke, Anders

AU - Ho, Tung Si

AU - Halvorsen, Trine Grønhaug

PY - 2005/7/1

Y1 - 2005/7/1

N2 - 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 μL of dodecyl acetate immobilized within the pores of a porous polypropylene hollow fibre (organic phase), and into 15 μL 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 μL 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.

AB - 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 μL of dodecyl acetate immobilized within the pores of a porous polypropylene hollow fibre (organic phase), and into 15 μL 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 μL 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.

KW - 2-phase extraction

KW - 3-phase extraction

KW - Carrier-mediated extraction

KW - Drugs

KW - Liquid-phase microextraction

KW - Plasma

KW - Porous hollow fibres

UR - http://www.scopus.com/inward/record.url?scp=23044502552&partnerID=8YFLogxK

U2 - 10.1002/jssc.200401935

DO - 10.1002/jssc.200401935

M3 - Journal article

C2 - 16116997

AN - SCOPUS:23044502552

VL - 28

SP - 1195

EP - 1203

JO - HRC &amp; CC, Journal of High Resolution Chromatography and Chromatography Communications

JF - HRC &amp; CC, Journal of High Resolution Chromatography and Chromatography Communications

SN - 1615-9306

IS - 11

ER -