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Citalopram, loperamide, methadone, paroxetine, pethidine, and sertraline were extracted exhaustively with electromembrane extraction (EME) by increasing the number of hollow fibers from one to three. Experiments reported recoveries in the range 97-115% from 1000μl spiked water samples. EME was accomplished with 200V as extraction voltage, the extraction time was set to 10min (equilibrium), and the extraction unit was subjected to 1200 revolutions per minute (rpm). The same experiment with different geometry in a stagnant system conducted with 21μl acceptor solution provided recoveries from 50μl undiluted human plasma (pH 7.4) in the range of 56-102% for the six basic model substances. In each experiment the acceptor solution was distributed into three separately hollow fibers in the same sample vial. The importance of an electrical field was verified by comparing EME with liquid-phase microextraction (LPME) under optimal conditions and demonstrated that the time needed to reach equilibrium was reduced by EME. EME-LC/MS provided linearity >0.99 (r(2) values) for the six basic model substances, and the repeatability within the low therapeutic range (10ng/ml) was in the range 5.1-21.4% RSD. LC-MS provided estimated limit of quantification (S/N=10) in the range 0.6-3.2ng/ml. Eventually, patient samples from a reference laboratory were analyzed and provided reliable results with a relative difference <14% compared to stated values from the reference laboratory., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The demand for automation of liquid-liquid extraction (LLE) in drug analysis combined with the demand for reduced sample preparation time has led to the recent development of liquid-phase microextraction (LPME) based on disposable hollow fibres. In LPME, target drugs are extracted from aqueous biological samples, through a thin layer of organic solvent immobilised within the pores of the wall of a porous hollow fibre, and into an microl volume of acceptor solution inside the lumen of the hollow fibre. After extraction, the acceptor solution is subjected directly to a final analysis either by high performance liquid chromatography (HPLC), capillary electrophoresis (CE), mass spectrometry (MS), or capillary gas chromatography (GC) without any further treatments. Hollow fibre-based LPME may provide high enrichment of drugs and excellent sample clean-up, and probably has a broad application potential within the area of drug analysis. This review focuses on the principle of LPME, and recent applications of three-phase, two-phase, and carrier mediated LPME of drugs from plasma, whole blood, urine, and breast milk.

Anabolic androgenic steroids (AAS) are metabolized extensively in the human body, resulting mainly in the formation of glucuronide conjugates. Current detection methods for AAS are based on gas chromatographic/mass spectrometric (GC/MS) analysis of the hydrolyzed steroid aglycones. These analyses require laborious sample preparation steps and are therefore time consuming. Our interest was to develop a rapid and straightforward method for intact steroid glucuronides in biological samples, using liquid-phase microextraction (LPME) sample clean-up and concentration method combined with liquid chromatographic/tandem mass spectrometric (LC/MS/MS) analysis. The applicability of LPME was optimized for 13 steroid glucuronides, and compared with conventional liquid-liquid extraction (LLE) and solid-phase extraction (SPE) procedures. An LC/MS/MS method was developed for the quantitative detection of AAS glucuronides, using a deuterium-labeled steroid glucuronide as the internal standard. LPME, owing to its high specificity, was shown to be better suited than conventional LLE and SPE for the clean-up of urinary AAS glucuronides. The LPME/LC/MS/MS method was fast and reliable, offering acceptable reproducibility and linearity with detection limits in the range 2-20 ng ml(-1) for most of the selected AAS glucuronides. The method was successfully applied to in vitro metabolic studies, and also tested with an authentic forensic urine sample. For a urine matrix the method still has some unsolved problems with specificity, which should be overcome before the method can be reliably used for doping analysis, but still offering additional and complementary data for current GC/MS analyses., (Copyright 2003 John Wiley & Sons, Ltd.)

Highlights: [•] A high-throughput electromembrane extraction platform has been developed. [•] In total 96 samples were processed in parallel within 10min of extraction. [•] The final extraction was directly compatible with mass spectrometry. [ABSTRACT FROM AUTHOR]

The demand for automation in analytical liquid-liquid extraction (LLE) combined with organic solvent reduction or elimination has led to the recent development of liquid-phase microextraction (LPME) based on disposable hollow fibres. In this concept, analytes of interest are extracted from aqueous samples, through a thin layer of organic solvent immobilized within the pores of a porous hollow fibre, and into an acceptor solution inside the lumen of the hollow fibre. Subsequently, the acceptor solution is directly subjected to a final analysis by capillary gas chromatography (CGC), high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), or mass spectrometry (MS) without any further effort. Hollow fibre-based LPME may provide high analyte pre-concentration and excellent sample clean-up, and it has a broad application potential within areas such as drug analysis and environmental monitoring. This review focuses on basic extraction principles, technical set-up, recovery, enrichment, extraction speed, selectivity, applications, and future trends in hollow fibre-based LPME. [Copyright &y& Elsevier]

Abstract: Amitriptyline, citalopram, fluoxetine, and fluvoxamine were isolated by electro membrane extraction (EME) from 70μl of untreated plasma (pH 7.4), through a supported liquid membrane (SLM) of 1-ethyl-2-nitrobenzene immobilized in the pores of a porous polypropylene hollow fiber, and into 30μl of 10mM HCOOH as acceptor solution inside the lumen of the hollow fiber. The driving force of the extraction was a 9V potential sustained over the SLM with a common battery, with the positive electrode placed in the plasma sample and the negative electrode placed in the acceptor solution. Extractions were performed under totally stagnant conditions with a very simple device for 1min (kinetic regime), and subsequently the acceptor solution was analyzed directly by liquid chromatography–mass spectrometry (LC–MS). Recoveries were 12, 13, 22, and 17% for fluoxetine, amitriptyline, citalopram, and fluvoxamine, respectively. Sample clean-up was comparable to reversed-phase solid-phase extraction (SPE), but EME required substantially less time than SPE. The time advantage of EME was further improved by parallel extraction of three samples (for 1min) with the same 9V battery. EME from plasma combined with LC–MS provided limits of quantification (S/N=10) in the range 0.4–2.3ng/ml, linearity in the range 1–1000ng/ml with r 2-values of 0.998–0.999, and repeatability in the range 3.2–8.9% RSD in the mid-therapeutic window (100ng/ml). [Copyright &y& Elsevier]

Abstract: For the first time, electromembrane extraction (EME) of six basic drugs of abuse from undiluted whole blood and post mortem blood in a totally stagnant system is reported. Cathinone, methamphetamine, 3,4-methylenedioxy-amphetamine (MDA), 3,4-methylenedioxy-methamphet-amine (MDMA), ketamine and 2,5-dimethoxy-4-iodoamphetamine (DOI) were extracted from the whole blood sample, through a supported liquid membrane (SLM) consisting of 1-ethyl-2-nitrobenzene (ENB) immobilized in the pores of a hollow fiber, and into an aqueous acceptor solution inside the lumen of the hollow fiber. The SLM acts as a barrier with efficient exclusion of all macromolecules and acidic substances in the sample. Due to the application of the electrical field, only the cationic compounds of interest are extracted efficiently across the membrane, thus providing extremely clean extracts for analysis with liquid chromatography–mass spectrometry, LC–MS. Recoveries in the range 10–30% were obtained from 80μl whole blood within 5min extraction time and an applied voltage of 15V across the SLM. The optimized technique was tested on real forensic whole blood samples taken from three forensic autopsy cases and on five forensic whole blood samples from living persons. The results were in agreement with the analysis using standard sample preparation methods (liquid–liquid extraction) performed on the same samples by Norwegian Institute of Public Health (NIPH), Division of Forensic Toxicology and Drug Abuse Research. Evaluation data were acceptable, with limit of detections (LODs) in the range 40–2610pg/mL, well below concentrations associated with drug abuse; linearites in the range between 10 and 250ng/mL with r 2 values above 0.9939, and with repeatability (RSD) of 7–32%. [Copyright &y& Elsevier]

Abstract: Recently, we demonstrated for the first time liquid-phase microextraction (LPME) of polar drugs based on carrier mediated transport. In this new extraction technique, selected analytes were extracted as ion-pairs from small volumes of biological samples, through a thin layer of a water immiscible organic solvent immobilised in the pores of a porous hollow fibre (liquid membrane), and into a μl volume of an acidic aqueous acceptor solution placed inside the lumen of the hollow fibre. In the current paper, this new extraction technique was combined with liquid chromatography–mass spectrometry (LC–MS) for the first time. Carrier mediated LPME was evaluated for several new model drugs (0.01&#60;log P &#60;1.76), the sample clean-up aspects were investigated in detail, and this new extraction technique was fully validated for the first time. Extractions were performed from 50μl of human plasma samples, which provided sufficient material in combination with LC–MS. Sodium octanoate (50mM) was added to the sample as carrier, 1-octanol (≈15μl) was used as the liquid membrane in the wall of the hollow fibre, and 50mM HCl was utilized as acceptor solution in the lumen of the hollow fibre. The addition of carrier to the samples was found to significantly improve extraction recoveries for the polar drugs tested, providing recoveries in the range 16–78%. Validation was accomplished for atenolol and cimetidine. Limits of quantification (S/N=5) from 50μl of plasma were 25 and 50ng/ml for atenolol and cimetidine, respectively. The intra-day precision (R.S.D.) ranged from 7.8 to 17.2% and from 9.5 to 14.1% for atenolol and cimetidine, respectively, and corresponding inter-day precisions (R.S.D.) were within 6.7–1.4% and 7.7–20.3%. The method was linear in the range 25–1500ng/ml for atenolol (r =0.992), and 50–3500ng/ml for cimetidine (r =0.976). The accuracy of the method was found to be in range 89.1–99.6% and 83.4–86% for atenolol and cimetidine, respectively. The sample clean-up obtained by carrier mediated LPME was excellent, providing a significantly lower back-ground level in total ion current chromatograms by LC–MS as compared to protein precipitation. [Copyright &y& Elsevier]