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Stig Pedersen-Bjergaard

Publications and source records attributed to Stig Pedersen-Bjergaard.

At least 19 recordsLinked to original sources
PubMed2006

Electrokinetic migration of acidic drugs across a supported liquid membrane.

Electrokinetic cross membrane extraction of acidic drugs was demonstrated for the first time. The acidic drugs were extracted from an alkaline aqueous donor solution (300 microl), through a thin supported liquid membrane of 1-heptanol sustained in the pores of the wall of a porous hollow fiber, and into an aqueous alkaline acceptor solution (30 microl) present inside the lumen of the hollow fiber by the application of a d.c. electrical potential. The negative electrode was placed in the donor solution, and the positive electrode was placed in the acceptor solution. Optimal extractions were accomplished with 1-heptanol as the supported liquid membrane, with 50 V as the driving force, and with pH 12.0 in both the donor and acceptor solutions, respectively (NaOH). Equilibrium extraction conditions were obtained after 5 min of operation with the whole assembly agitated at 1200 rpm. Eleven different acidic drugs were extracted with recovery values between 8 and 100%, and initial data supported that electrokinetic cross membrane extraction provided repeatable data and linear response between original donor concentration and final acceptor concentration of the acidic model compounds.

Acids↗
PubMed2006

Electrokinetic migration across artificial liquid membranes Tuning the membrane chemistry to different types of drug substances.

Twenty different basic drugs were electrokinetically extracted across a thin artificial organic liquid membrane with a 300 V d.c. electrical potential difference as the driving force. From a 300 microl aqueous sample (acidified corresponding to 10mM HCl), the drugs were extracted for 5 min through a 200 microm artificial liquid membrane of a water immiscible organic solvent immobilized in the pores of a polypropylene hollow fiber, and into a 30 microl aqueous acceptor solution of 10mM HCl inside the lumen of the hollow fiber. Hydrophobic basic drugs (logP>1.7) were effectively isolated utilizing 2-nitrophenyl octyl ether (NPOE) as the artificial liquid membrane, with recoveries up to 83%. For more hydrophilic basic drugs (logP<1.0), a mixture of NPOE and 25% (w/w) di-(2-ethylhexyl) phosphate (DEHP) was required to ensure efficient extraction, resulting in recoveries up to 75%. DEHP was expected to act as an ion-pair reagent ion-pairing the protonated hydrophilic drugs at the interface between the sample and the membrane, resulting in permeation of the interface.

Chromatography, Micellar Electrokinetic Capillary↗
PubMed2006

Electrokinetic migration across artificial liquid membranes. New concept for rapid sample preparation of biological fluids.

Basic drug substances were transported across a thin artificial organic liquid membrane by the application of 300 V d.c. From a 300 microl aqueous donor compartment (containing 10 mM HCl), the drugs migrated through a 200 microm artificial liquid membrane of 2-nitrophenyl octyl ether immobilized in the pores of a polypropylene hollow fiber, and into a 30 microl aqueous acceptor solution of 10 mM HCl inside the lumen of the hollow fiber. The transport was forced by an electrical potential difference sustained over the liquid membrane, resulting in electrokinetic migration of drug substances from the donor compartment to the acceptor solution. Within 5 min of operation at 300 V, pethidine, nortriptyline, methadone, haloperidol, and loperamide were extracted with recoveries in the range 70-79%, which corresponded to enrichments in the range 7.0-7.9. The chemical composition of the organic liquid membrane strongly affected the permeability, and may serve as an efficient tool for controlling the transport selectivity. Water samples, human plasma, and human urine were successfully processed, and in light of the present report, electrokinetic migration across thin artificial liquid membranes may be an interesting tool for future isolation within chemical analysis.

Chromatography, Micellar Electrokinetic Capillary↗
PubMed2006

Analytical microextraction: current status and future trends.

Analytical microextractions, defined as nonexhaustive sample preparation with a very small volume of extracting phase (microliter range or smaller) relative to the sample volume, represent an important development in the field of analytical chemistry. Analytes are extracted by a small volume of a solid or semi-solid polymeric material, as in solid-phase microextraction (SPME), or alternatively by a small volume of a liquid, as in liquid-phase microextraction (LPME). This paper gives an overview of the SPME and LPME techniques and discusses future trends. This includes a discussion of the different extraction formats available, commercial equipment, method transfer from traditional sample preparation methods to microextraction, and performance as well as robustness for the latter type of systems. In addition, the paper contains a unified approach to the understanding of extraction thermodynamics and kinetics applicable to both SPME and LPME.

Chemical Fractionation↗
PubMed2006

Experiences with carrier-mediated transport in liquid-phase microextraction.

Different organic borates, phosphates, sulphates, and carboxylic acids are evaluated as extraction carriers in three-phase liquid-phase microextraction (LPME). Hydrophilic basic drugs form ion-pairs with the carriers and are extracted as ion-pair complexes into an organic liquid membrane of n-octanol or peppermint oil immobilized in the pores of a polypropylene hollow fiber. From this point, the basic drugs are released into a 20-microL solution of 50mM HCl placed inside the lumen of the hollow fiber (acceptor solution). Simultaneously, the carrier is neutralized by protons from the acceptor solution (protonated to maintain the charge balance). Both water-soluble and water-insoluble carriers are tested. One promising candidate among the water-soluble carriers is 1-heptanesulfonic acid. This is added to the sample solution to a final concentration of 25mM and served to ion-pair the analytes within the sample solution. Among the less water-soluble candidates, a mixture of di(2-ethylhexyl) phosphate (DEHP) and tris(2-ethylhexyl) phosphate (TEHP) serve as efficient carriers. Ten percent (w/w) of each of DEHP and TEHP are added to the organic liquid membrane, and these carriers principally worked through ion-pairing with the analytes at the interface between the sample solution and the organic liquid membrane. Several carriers are found to be compatible with human plasma samples, and bromthymol blue is particularly efficient in combination with these protein-containing matrices. Following optimization of the conditions for bromthymol blue, including saturation of the plasma samples with sodium sulphate, extraction recoveries between 45% and 75% are obtained for eight model drugs after 60 min of extraction. With bromthymol blue as the carrier, highly acceptable validation data are obtained for phenylpropanolamine and practolol extracted from human plasma.

Anions↗
PubMed2005

Liquid-phase microextraction based on carrier mediated transport combined with liquid chromatography-mass spectrometry. New concept for the determination of polar drugs in a single drop of human plasma.

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 microl 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 <log P< 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 50 microl of human plasma samples, which provided sufficient material in combination with LC-MS. Sodium octanoate (50 mM) was added to the sample as carrier, 1-octanol (approximately 15 microl) was used as the liquid membrane in the wall of the hollow fibre, and 50 mM 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 50 microl of plasma were 25 and 50 ng/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 25-1500 ng/ml for atenolol (r = 0.992), and 50-3500 ng/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.

Amphetamine↗
PubMed2005

Bioanalysis of drugs by liquid-phase microextraction coupled to separation techniques.

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.

Body Fluids↗
PubMed2005

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.

Humans↗
PubMed2004

State-of-the art of selective detection and identification of I-, Br-, Cl-, and F-containing compounds in gas chromatography and liquid chromatography.

This review article presents an overview of halogen-specific detection in gas chromatography (GC) and liquid chromatography (LC). Attention is primarily focused on the use of plasma emission spectroscopy and plasma mass spectrometry as detectors, but other halogen-selective detection principles are also mentioned. Different instrumental configurations are discussed both with respect to technical set-up and performance, the principal reasons for halogen-selective detection are highlighted, and recent applications are reviewed from areas such as environmental chemistry, petroleum characterization, and drug analysis.

Animals↗
PubMed2004

Screening for central nervous system-stimulating drugs in human plasma by liquid chromatography with mass spectrometric detection.

Liquid chromatography and electrospray mass spectrometry was evaluated for screening of more than 70 central nervous system-stimulating drugs in human plasma. Protein precipitation was utilized as a simple sample preparation procedure, and the subsequent screening procedure involved two injections in a liquid chromatography-mass spectrometry system for each sample; a first screening without source induced dissociation to maximize sensitivity where potential positive identifications were based on retention time and molecular ion masses, and secondly a source induced dissociation confirmation based on retention time, molecular ions, and one or two fragment ions for each target generated by a 25 V fragmentation energy. The majority of central nerve system stimulating drugs were possible to identify within the actual therapeutic ranges. Experiences with 175 real samples supported this and strongly indicated that information reported by patients on their consumption of central nerve system stimulating drugs is highly unreliable. Thus, protein precipitation and liquid chromatography-mass spectrometry may be a valuable tool for broad drug screening in human plasma in the future.

Central Nervous System Stimulants↗
PubMed2004

Liquid-phase microextraction utilising plant oils as intermediate extraction medium--towards elimination of synthetic organic solvents in sample preparation.

Hollow fibre based liquid-phase microextraction (LPME) using fatty oils and essential oils as the organic phase was evaluated to develop sample preparation technology eliminating the use of hazardous organic solvents. Basic drugs were extracted from different aqueous samples (0.2 to 1 mL) through approximately 15 microL of either almond oil, arachis oil, olive oil, soy-bean oil, anise oil, fennel oil, lavender oil, or peppermint oil (organic phase) immobilised within the pores of a polypropylene hollow fibre and into 20 microL of 10 mM HCOOH (acceptor phase) present inside the lumen of the hollow fibre. The extraction performance of the essential oils was comparable with the solvents normally used in LPME (dihexyl ether, n-octanol, and dodecyl acetate) in terms of extraction recovery and extraction speed. Whereas all essential oils tested were compatible with human urine, only anise oil was successful for plasma. The fatty oils provided lower recoveries than the essential oils due to higher viscosity, but all the fatty oils were compatible both with urine and plasma samples. In spite of the multi-component nature of the oils tested, they were not found to seriously contaminate the acceptor phases during extraction. In conclusion, fatty oils and essential oils may serve as alternative organic phase in LPME, eliminating the use of hazardous organic solvents.

Mentha piperita↗
PubMed2003

Stereospecific determination of citalopram and desmethylcitalopram by capillary electrophoresis and liquid-phase microextraction.

A chiral capillary electrophoresis (CE) system allowing simultaneous enantiomer determination of citalopram (CIT) and its pharmacologically active metabolite desmethylcitalopram (DCIT) was developed. Excellent chiral separation was obtained using 1% sulfated-beta-cyclodextrin (S-beta-CD) as chiral selector in combination with 12% ACN in 25 mM phosphate pH 2.5. Samples were prepared by liquid-phase microextraction (LPME) based on a rodlike porous polypropylene hollow fibre. CIT and DCIT were extracted from 1 ml plasma made alkaline with NaOH, into dodecyl acetate impregnated in the pores of a hollow fibre, and into 20 mM phosphate pH 2.75, inside the hollow fibre. The acceptor solution was directly compatible with the CE system. Efficient sample clean-up was seen, and the recoveries were 46 and 29% for the enantiomers of CIT and DCIT, respectively, corresponding to 31 and 19 times enrichment. The limit of quantification (S/N=10) was <11.2 ng/ml, intra-day precision was <12.8% RSD, and inter-day precision was <14.5% RSD, for all enantiomers. The validated method was successfully applied to simultaneous determination of enantiomer concentrations of CIT and DCIT in plasma samples from nine patients treated with racemic citalopram. The results confirm LPME-CE as a suitable and promising tool for enantiomeric determination of chiral drugs and metabolites in biological matrices.

Adolescent↗
PubMed2003

Liquid-phase microextraction of hydrophilic drugs by carrier-mediated transport.

Basic studies on carrier-mediated transport as a mechanism to extract polar drugs by hollow fibre-based liquid-phase microextraction are presented for the first time. Hydrophilic alkaline drugs with log P (octanol/water partition coefficient) values less than 1 were selected as model substances. Sodium octanoate served as carrier and was added to the sample solution at pH 7 to form hydrophobic ion-pair complexes with the analytes. The ion-pair complexes were extracted into octanol as liquid membrane immobilised in the pores of the hollow fibre. Further extraction into an aqueous acceptor phase inside the lumen of the hollow fibre was facilitated by counter transport of protons from the acceptor solution to the sample solution. Protons from the acceptor solution released the analytes at the liquid membrane-acceptor interface and neutralized the carrier. The acceptor phase was analysed by capillary electrophoresis. The studies show that high extraction recoveries of ionic hydrophilic drugs can be obtained at a sample-acceptor volume ratio of 10. Linear calibration graphs and clean electropherograms indicate that carrier-mediated transport is a promising technique in microextraction of polar drugs from biological matrices.

Calibration↗
PubMed2003

Feasibility of a liquid-phase microextraction sample clean-up and liquid chromatographic/mass spectrometric screening method for selected anabolic steroid glucuronides in biological samples.

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.

Anabolic Agents↗
PubMed2002

Recovery, enrichment and selectivity in liquid-phase microextraction comparison with conventional liquid-liquid extraction.

Mathematical descriptions for extraction recovery and enrichment were applied for liquid-phase microextraction (LPME) and comparison with conventional two- and three-phase liquid-liquid extraction techniques (LLE) was made. The LPME theoretical calculations were verified by experimental determination of actual partition coefficients and by data obtained with LPME in a robust hollow fibre formate. With hollow fibre LPME operated in the two-phase mode, analytes were extracted from 1 to 4 ml aqueous samples into 25-50 microl of an organic solvent present in the pores and in the lumen of the porous hollow fibres. Compared with conventional two-phase LLE, two-phase LPME provided substantially higher enrichments for compounds with relatively large partition coefficients (K(org)/d>500). In contrast, because of the large volume of organic solvent relative to the sample volume, LLE provided high recovery and moderate enrichment even for compounds with relatively low partition coefficients (K(org)/d>5). Thus, two-phase LPME may be used for substantially enhanced extraction selectivity and enrichment of relatively hydrophobic analytes as compared with LLE whereas conventional two-phase LLE is superior for more hydrophilic analytes. Similar results were found for three-phase LPME where analytes where extracted from 1 to 4 ml aqueous samples through approximately 20 microl organic solvent immobilized within the pores of the hollow fibre and into 25 microl of an aqueous acceptor solution inside the lumen of the hollow fibre. The fundamental differences of LPME and LLE were further demonstrated with practical experiments on extraction of the basic drugs promethazine, methadone, and haloperidol from human plasma and urine.

Chromatography, Gas↗
PubMed2002

Liquid-phase microextraction combined with capillary electrophoresis, a promising tool for the determination of chiral drugs in biological matrices.

A disposable device for liquid-phase microextraction (LPME) based on porous polypropylene hollow fibres has recently been introduced. In the present paper, LPME was combined with capillary electrophoresis (CE) and the combination was for the first time evaluated for chiral determination of drugs in biological matrices. The chiral antidepressant drug mianserin was selected as model compound. The mianserin enantiomers were extracted from 0.5 ml of plasma added internal standard and made alkaline with 0.25 ml of 2 M NaOH. The unionised analytes were extracted into di-n-hexyl ether impregnated in the pores of the hollow fibre, and into an acidic solution inside the hollow fibre. This resulted in a three-phase system where the extracts were aqueous, and hence directly compatible with the CE system. Efficient sample clean-up was seen and the extraction recovery was 80% for both enantiomers. Discrimination between the enantiomers in the extraction system was not observed. The limit of quantitation (S/N= 10; 12.5 ng/ml for both enantiomers) and the limit of detection (S/N=3; 4 ng/ml for both enantiomers) were below the therapeutic range for mianserin. The method was validated and successfully applied to determine R- and S-mianserin in plasma samples from seven patients treated with mianserin, indicating that LPME-CE is a promising combination for analysis of racemic drugs present in low concentrations in biological matrices.

Calibration↗
PubMed2002

Solid-phase microextraction coupled with atomic emission spectroscopy--rapid screening for volatile chlorinated compounds.

Solid-phase microextraction (SPME) coupled with atomic emission spectroscopy was evaluated as a rapid screening tool for volatile halogenated compounds in water samples. After extraction, the SPME fiber was introduced to the injector where the analytes were rapidly and efficiently desorbed. The analytes entered the detector over a short period of time and produced one well-defined analyte signal. Element selective responses were measured to confirm the presence and to roughly estimate the content of volatile compounds. The total time for extraction and detection was approximately 5 min, which makes this method a rapid and promising technique for determination of total amount of volatile halogenated compounds. The proposed technique may prove useful as a screening test in order to pinpoint the samples that need further assessment by capillary gas chromatography.

Chemistry Techniques, Analytical↗