Liquid-phase microextraction of protein-bound drugs under non-equilibrium conditions

Abstract

Recently, we introduced an inexpensive and disposable hollow fiber-based device for liquid-phase microextraction (LPME) where ionic analytes typically were extracted and preconcentrated from 1-4 mL aqueous samples (such as plasma and urine) through an organic solvent immobilized in the pores of a polypropylene hollow fiber and into a 10-25 microL volume of acceptor phase present inside the lumen of the hollow fiber. Subsequently, the acceptor phase was directly subjected to the final analysis by a chromatographic or electrophoretic method. In the present work, attention was focused on LPME of the basic drugs amphetamine, pethidine, promethazine, methadone and haloperidol characterized by substantial differences in the degree of protein binding. Drug-protein interactions in plasma resulted in reduced recoveries and substantially increased extraction times compared with extraction of the drugs from a pure water matrix. However, by addition of 5-50% methanol to the plasma samples, recoveries were comparable with LPME from water samples and ranged between 75 and 100%. The addition of methanol was found not to speed up the LPME process and extractions from plasma were performed in 45 min to reach equilibrium. Because approximately 55-70% of the final analyte concentrations were achieved within the initial 10 min of the LPME process, validation was accomplished after 10 and 45 min of LPME. In general, the results with 10 and 45 min were almost comparable, with precision data in the range 1.2-11.1% (RSD) and with linearity in the concentration range 20-1000 ng mL(-1) (r = 0.999). In conclusion, excellent LPME results may be achieved in a short time under non-equilibrium conditions with a minor loss of sensitivity. In cases of drug-protein interactions, methanol may be added to ensure a high extraction recovery.

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

“…Thus, the recovery values reported may be improved by further method optimization. Extraction times of 60 min were selected in this fundamental work to present equilibrium data; however, a recent publication has shown that rapid LPME may be carried out under nonequilibrium conditions with only slightly reduced recovery and with no performance reduction with respect to validation parameters [13].…”

Current Trends in Liquid-Liquid Microextraction for Analysis of Pesticide Residues in Food and Water

“…Normally, extraction time range between 15 and 45 min for sample volumes below 2 mL, whereas for 1 L samples even 2 h may be required to reach equilibrium (Pedersen-Bjergaard & Rasmussen, 2008). Recently, some proposals have been made in order to speed up the throughput of the procedure, either by treating many samples in parallel, carrying out the extraction under non-equilibrium condition (Ho et al 2002), or using the so called dynamic hollow fiber protected liquid phase microextraction (DHFP-LPME). The latter technique was successful applied by Huang & Huang (2006) in the extraction of OCPs from green tea leaves and ready-to-drink tea prior to GC-ECD analysis.…”

Microextração em fase líquida (LPME): fundamentos da técnica e aplicações na análise de fármacos em fluidos biológicos

“…Neste sentido, Ho et al 51 estudaram o efeito de diferentes estratégias para supressão destas interações e observaram que, dependendo das características do analito, a adição de metanol em diferentes proporções pode ser útil. Outros trabalhos envolvendo a análise de fármacos no plasma são descritos na literatura (Tabela 1).…”