Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease.

BACKGROUND: Limited data are available on the long-term effects of contemporary drug-eluting stents versus contemporary bare-metal stents on rates of death, myocardial infarction, repeat revascularization, and stent thrombosis and on quality of life. METHODS: We randomly assigned 9013 patients who had stable or unstable coronary artery disease to undergo percutaneous coronary intervention (PCI) with the implantation of either contemporary drug-eluting stents or bare-metal stents. In the group receiving drug-eluting stents, 96% of the patients received either everolimus- or zotarolimus-eluting stents. The primary outcome was a composite of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularization, stent thrombosis, and quality of life. RESULTS: At 6 years, the rates of the primary outcome were 16.6% in the group receiving drug-eluting stents and 17.1% in the group receiving bare-metal stents (hazard ratio, 0.98; 95% confidence interval [CI], 0.88 to 1.09; P=0.66). There were no significant between-group differences in the components of the primary outcome. The 6-year rates of any repeat revascularization were 16.5% in the group receiving drug-eluting stents and 19.8% in the group receiving bare-metal stents (hazard ratio, 0.76; 95% CI, 0.69 to 0.85; P<0.001); the rates of definite stent thrombosis were 0.8% and 1.2%, respectively (P=0.0498). Quality-of-life measures did not differ significantly between the two groups. CONCLUSIONS: In patients undergoing PCI, there were no significant differences between those receiving drug-eluting stents and those receiving bare-metal stents in the composite outcome of death from any cause and nonfatal spontaneous myocardial infarction. Rates of repeat revascularization were lower in the group receiving drug-eluting stents. (Funded by the Norwegian Research Council and others; NORSTENT ClinicalTrials.gov number, NCT00811772 .).

Trends in Modifiable Risk Factors Are Associated With Declining Incidence of Hospitalized and Nonhospitalized Acute Coronary Heart Disease in a Population.

BACKGROUND: Few studies have used individual person data to study whether contemporary trends in the incidence of coronary heart disease are associated with changes in modifiable coronary risk factors. METHODS AND RESULTS: We identified 29 582 healthy men and women ≥25 years of age who participated in 3 population surveys conducted between 1994 and 2008 in Tromsø, Norway. Age- and sex-adjusted incidence rates were calculated for coronary heart disease overall, out-of-hospital sudden death, and hospitalized ST-segment-elevation and non-ST-segment-elevation myocardial infarction. We measured coronary risk factors at each survey and estimated the relationship between changes in risk factors and changes in incidence trends. A total of 1845 participants had an incident acute coronary heart disease event during 375 064 person-years of follow-up from 1994 to 2010. The age- and sex-adjusted incidence of total coronary heart disease decreased by 3% (95% confidence interval, 2.0-4.0; P<0.001) each year. This decline was driven by decreases in out-of-hospital sudden death and hospitalized ST-segment-elevation myocardial infarction. Changes in coronary risk factors accounted for 66% (95% confidence interval, 48-97; P<0.001) of the decline in total coronary heart disease. Favorable changes in cholesterol contributed 32% to the decline, whereas blood pressure, smoking, and physical activity each contributed 14%, 13%, and 9%, respectively. CONCLUSIONS: We observed a substantial decline in the incidence of coronary heart disease that was driven by reductions in out-of-hospital sudden death and hospitalized ST-segment-elevation myocardial infarction. Changes in modifiable coronary risk factors accounted for 66% of the decline in coronary heart disease events.

Incidence of aortic stenosis in subjects with normal and slightly elevated aortic gradients and flow.

OBJECTIVE: We aimed to describe the progression rate into manifest aortic stenosis (AS) in subjects with normal aortic valves or in an early phase of calcific aortic valve disease. METHODS: Participants were recruited from the Tromsø Study, a population-based health survey. In our prospective cohort study, we performed two echocardiographical examinations (2001 and 2008) of a random sample of 1884 participants. AS was defined as a mean aortic valve gradient ≥15 mm Hg or a peak flow exceeding 2.6 m/s. Those with lesser values were stratified into three groups based on mean gradients (cut-off 5 and 10 mm Hg) and peak aortic flow (cut-off 1.5 and 2 m/s). RESULTS: At baseline, 71 participants had gradients from 10 to 14.9 mm Hg, of whom 32.4% developed AS during follow-up. AS developed in only 3.6% of those with a baseline gradient of 5-9.9 mm Hg and in 0.3% of those with a gradient <5 mm Hg. Almost identical separations were obtained among the three flow velocity groups. Of the 45 subjects who developed incident AS, 56% acquired mild, 33% moderate and 11% severe AS. Their mean gradient progression rate was 2.7 mm Hg/year. CONCLUSIONS: The results support that subjects with a mean aortic valve gradient of 10-15 mm Hg or aortic flow >2.0 m/s should be followed routinely. This group identifies about half of those who develop AS in the following 7 years.

Assessment of risk factors for developing incident aortic stenosis: the Tromsø Study.

To disclose risk factors of incident aortic stenosis (AS) and progression of established AS. A prospective cohort study. The Tromsø Study, a population based health survey. Over a 14 years span we performed three repeated echocardiographic examinations (1994, 2001 and 2008) of a random sample of initially 3,243 participants. Data from the only hospital serving this population were included in the follow up. Throughout the study 132 participants were diagnosed with incident AS, defined as mean aortic valve gradient ≥15 mmHg. Cox proportional hazards regression disclosed age (HR 1.11, 95 %CI 1.08-1.14), systolic blood pressure (BP) (HR 1.01, 95 % CI 1.00-1.02), active smoking (HR 1.71, 95 % CI 1.09-2.67), and waist circumference (HR 1.02, 95 % CI 1.00-1.03) as independent predictors of incident AS. Analysis of risk factors for progression of AS disclosed a higher mean aortic gradient at first measurement (p = 0.015), weight (p = 0.015), a low haemoglobin (Hgb) (p = 0.030) and high density lipoprotein (HDL) (p = 0.032) as significant independent predictors. Age, systolic BP, smoking and waist circumference were independent predictors of incident AS, whereas cholesterol was not. Mean aortic gradient at first measurement, weight, an elevated HDL and low Hgb increase the progression rate of the disease. Our data indicate that calcific aortic valve disease is a distinct pathophysiological process, with age, smoking and "wear and tear" of the valve being major contributors to the disease development.

Parallel electromembrane extraction in the 96-well format.

The repeatability and extraction recoveries of parallel electromembrane extraction (Pa-EME) was thoroughly investigated in the present project. Amitriptyline, fluoxetine, and haloperidol were isolated from eight samples of pure water, undiluted human plasma, and undiluted human urine, respectively; in total 24 samples were processed in parallel. The repeatability was found to be independent of the different sample matrices (pure water samples, human plasma, and water) processed in parallel, although the respective samples contained different matrix components. In another experiment seven of the 24 wells were perforated. Even though the perforation caused the total current level in the Pa-EME setup to increase, the intact circuits were unaffected by the collapse in seven of the circuits. In another approach, exhaustive extraction of amitriptyline, fluoxetine, and haloperidol was demonstrated from pure water samples. Amitriptyline and haloperidol were also isolated exhaustively from undiluted human plasma samples; the extraction recovery of fluoxetine from undiluted human plasma was 81%. Finally, the sample throughput was increased with the Pa-EME configuration. The extraction recoveries were investigated by processing 1, 8, 68, or 96 samples in parallel in 10min; neither the extraction recoveries nor the repeatability was affected by the total numbers of samples. Eventually, the Pa-EME was combined with ultra performance liquid chromatography (UPLC) to combine high-throughput sample preparation with high-throughput analytical instrumentation. The aim of the present investigation was to demonstrate the potential of electromembrane extraction as a high throughput sample preparation platform; and hopefully to increase the interest for EME in the bioanalytical field to solve exisiting and novel analytical challenges.

Parallel electromembrane extraction in a multiwell plate.

This paper describes the concept of parallel electromembrane extraction (Pa-EME) with flat membranes in a multiwell format for the first time. The setup is based on a multiwell plate and provided simultaneous and selective isolation, cleanup, and enrichment of several human plasma samples as well as LC-MS-compatible extracts within 8 min of extraction. Undiluted human plasma samples spiked with four antidepressant drugs were added to separate wells in the donor plate. Subsequently, the samples were extracted with Pa-EME. The four drugs migrated electrokinetically from undiluted human plasma through a flat polypropylene membrane impregnated with 2-nitrophenyl octyl ether, and were isolated into formic acid. Extraction time, extraction voltage, agitation rate, sample volume, and acceptor solution volume were all optimized with an experimental design. The optimal conditions were as follows: The agitation rate was 1,040 rpm, and an extraction voltage of 200 V was applied. The sample volume and acceptor solution volume was 240 and 70 µL, respectively. The extraction was continued for 8 min. Eventually, the extracts were analyzed by LC-MS/MS. The combination of Pa-EME with LC-MS/MS provided quantitation limits below the therapeutic level and reported relative standard deviations in the range 5-13 %. Linear calibration curves were obtained for all analytes, and the correlation coefficients were above 0.9974 in the range 1-400 ng mL(-1). The drug concentrations from two subjects treated with quetiapine and sertraline were successfully determined with Pa-EME combined with LC-MS/MS. Post-column infusion experiments demonstrated that Pa-EME provided extracts free from interfering matrix components.

Parallel artificial liquid membrane extraction: micro-scale liquid-liquid-liquid extraction in the 96-well format.

BACKGROUND: This paper reports development of a new approach towards analytical liquid-liquid-liquid membrane extraction termed parallel artificial liquid membrane extraction. A donor plate and acceptor plate create a sandwich, in which each sample (human plasma) and acceptor solution is separated by an artificial liquid membrane. Parallel artificial liquid membrane extraction is a modification of hollow-fiber liquid-phase microextraction, where the hollow fibers are replaced by flat membranes in a 96-well plate format. RESULTS: Four basic drugs (pethidine, nortriptyline, methadone and haloperidol) were extracted from human plasma in 30 min, followed by analysis with LC-MS/MS. Extraction recoveries for the model analytes were in the range of 34-74% from human plasma. LOQs were in the range of 0.01-0.35 ng/ml, linearity above 0.9955 for all drugs and with RSD values below 12%. CONCLUSION: Liquid-liquid-liquid membrane extraction was successfully performed in a slightly modified commercially available 96-well plate format.

Storage of oral fluid as dried spots on alginate and chitosan foam - a new concept for oral fluid collection.

BACKGROUND: In recent years, there has been a major focus on analyzing drug substances from dried µl volumes of biological fluids, commonly known as dried matrix spotting. RESULTS: 10 µl oral fluid, spiked with five basic drugs, was collected and stored as dried spots on alginate and chitosan foam, and subsequently dissolved; the drugs were thereafter isolated with electromembrane extraction and analyzed by LC-MS. The correlation coefficients were above 0.9885 for all drugs in the range 25-1000 ng/ml. The reported RSD values were below 15%. CONCLUSION: Storage of oral fluid as dried spots on alginate and chitosan foam have been investigated for the first time. The extract obtained after electromembrane extraction was directly compatible with LC-MS, and apparently free from coextracted matrix components.

The evolving epidemiology of valvular aortic stenosis. the Tromsø study.

OBJECTIVE: To assess prevalence, incidence, prognosis and progression of degenerative valvular aortic stenosis (AS). SETTING: The Tromsø Study and the University Hospital of North Norway. DESIGN: Population based prospective study. POPULATION: Over a 14 year span we performed three repeated echocardiographic examinations (1994, 2001 and 2008) of a random sample of initially 3273 participants. Data from the only hospital serving this population were included. RESULTS: There were 164 subjects with AS. Prevalence consistently increased with age, average values being 0.2% in the 50-59 year cohort, 1.3% in the 60-69 year cohort, 3.9% in the 70-79 year cohort and 9.8% in the 80-89 year cohort. The incidence rate in the study was 4.9‰/year. The mean annual increase in mean transvalvular pressure gradient was 3.2 mm Hg. The increase was lower in mild AS than in more severe disease, disclosing a non-linear development of the gradient, but with large individual variations. Mortality was not significantly increased in the asymptomatic AS-group (HR = 1.28), nor in those who received aortic valve replacement (n = 34, HR = 0.93), compared with the general population. CONCLUSION: This is the first study to document the incidence and prognosis of AS in a general population with surgery as a treatment option. It reveals an accelerated progression of the aortic mean gradient as the disease advances. The prognosis of AS seems to be comparable with the normal population in the asymptomatic stage and after successful surgery, indicating that the follow-up and timing of surgery has been adequate for this patient group.

Alginate and chitosan foam combined with electromembrane extraction for dried blood spot analysis.

Samples of 10 µL of whole blood containing citalopram, loperamide, methadone, and sertraline as model substances were spotted on alginate and chitosan foams as sampling media. After drying and storage at room temperature, the punched out dried blood spot and the foam was dissolved in 300 µL of 1 mM HCl. With alginate foam as sampling medium, the analytes dissolved completely after 3 min. Enrichment and cleanup was performed with electromembrane extraction for 10 min. The analytes were collected in 21 µL of 10 mM formic acid as the acceptor phase, and the extracts were analyzed by liquid chromatography-mass spectrometry (LC-MS). Sample preparation of blood spots on commercial cards was also performed (Whatman FTA DMPK and Agilent Bond Elut DMS) using elution procedures recommended by the manufacturers. The recoveries obtained with the commercial cards were lower for most of the model analytes compared to the recoveries obtained with alginate and chitosan foams as sampling media. The procedure used for Agilent Bond Elut DMS showed higher recoveries than the procedure used for Whatman FTA DMPK-A, but the time needed for sample preparation was significantly longer (nearly 2 h). The stability of the model substances on the alginate foam was acceptable within 50 days of storage. The limit of quantification (LOQ) defined as S/N = 10, was 1.2, 5.5, 2.0, and 5.3 ng/mL for citalopram, loperamide, methadone, and sertraline, respectively. Linear calibration graphs were obtained in the range 17.5-560 ng/mL with r(2) values 0.983-0.995, and the relative standard deviations were below 20%.

Kinetic aspects of hollow fiber liquid-phase microextraction and electromembrane extraction.

In this paper, extraction kinetics was investigated experimentally and theoretically in hollow fiber liquid-phase microextraction (HF-LPME) and electromembrane extraction (EME) with the basic drugs droperidol, haloperidol, nortriptyline, clomipramine, and clemastine as model analytes. In HF-LPME, the analytes were extracted by passive diffusion from an alkaline sample, through a (organic) supported liquid membrane (SLM) and into an acidic acceptor solution. In EME, the analytes were extracted by electrokinetic migration from an acidic sample, through the SLM, and into an acidic acceptor solution by application of an electrical potential across the SLM. In both HF-LPME and EME, the sample (donor solution) was found to be rapidly depleted for analyte. In HF-LPME, the mass transfer across the SLM was slow, and this was found to be the rate limiting step of HF-LPME. This finding is in contrast to earlier discussions in the literature suggesting that mass transfer across the boundary layer at the donor-SLM interface is the rate limiting step of HF-LPME. In EME, mass transfer across the SLM was much more rapid due to electrokinetic migration. Nevertheless, mass transfer across the SLM was rate limiting even in EME. Theoretical models were developed to describe the kinetics in HF-LPME, in agreement with the experimental findings. In HF-LPME, the extraction efficiency was found to be maintained even if pH in the donor solution was lowered from 10 to 7-8, which was below the pK(a)-value for several of the analytes. Similarly, in EME, the extraction efficiency was found to be maintained even if pH in the donor solution increased from 4 to 11, which was above the pK(a)-value for several of the analytes. The two latter experiments suggested that both techniques may be used to effectively extract analytes from samples in a broader pH range as compared to the pH range recommended in the literature.

Selective electromembrane extraction at low voltages based on analyte polarity and charge.

Electromembrane extraction (EME) at low voltage (0-15 V) of 29 different basic model drug substances was investigated. The drug substances with logP<2.3 were not extracted at voltages less than 15 V. Extraction of drug substances with logP≥2.3 and with two basic groups were also effectively suppressed by the SLM at voltages less than 15 V. Drug substances with logP≥2.3 and with one basic group were all extracted at low voltages and with a strong compound selectivity which appeared to have some influence from the polar surface area of the compound. For this group of substances, recoveries varied between 0 and 23% at 5 V, whereas, recoveries varied between 5.5 and 51% at 15 V. Based on mass transfer differences related to charge, polarity, and polar surface, highly selective extractions of drug substances were demonstrated from human plasma, urine, and breast milk. An initial evaluation at low voltage (5 V) was compared with similar extractions at a more normal voltage level (50 V), and this supported that reliable data can be obtained under these low-voltage (mild) conditions by EME.

Electromembrane extraction of stimulating drugs from undiluted whole blood.

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 80 µl whole blood within 5 min 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 40-2610 pg/mL, well below concentrations associated with drug abuse; linearites in the range between 10 and 250 ng/mL with r(2) values above 0.9939, and with repeatability (RSD) of 7-32%.

Age and gender differences in incidence and case fatality trends for myocardial infarction: a 30-year follow-up. The Tromso Study.

BACKGROUND: Although the mortality of coronary heart disease (CHD) has declined in Western countries during the last decades, studies have suggested that the prevention and treatment of CHD may not have been as effective in women as in men. We examined gender- and age-specific trends in incidence, case fatality and the severity of first myocardial infarction (MI) in a large Norwegian population-based study. DESIGN: Prospective population-based cohort study. METHODS: A total of 31,323 participants enrolled between 1974 and 2001 were followed throughout 2004 for a total of 400,572 person-years. Suspected coronary events were adjudicated by a review of hospital records and death certificates. A total of 1669 events fulfilled standardized criteria of first-ever fatal or non-fatal MI. RESULTS: In the age group 35-79 years, the age-adjusted incidence of MI declined significantly in men, whereas an increase was observed in women. For men and women ≥ 80 years the incidence rates remained unchanged. The severity of MI and the 28-day and 1-year case fatality rates declined significantly and similarly in men and women. CONCLUSION: Trends in MI incidence differed by sex and age; in the age group 35-79 years a marked decrease was observed among men but an increase was observed among women, while no change was observed among older patients. MI severity and case fatality were clearly reduced for both sexes. These data suggest that the burden of CHD is shifting from middle-aged men toward middle-aged women and elderly patients.

Exhaustive electromembrane extraction of some basic drugs from human plasma followed by liquid chromatography-mass spectrometry.

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.

Electromembrane extraction and HPLC analysis of haloacetic acids and aromatic acetic acids in wastewater.

For the first time, haloacetic acids and aromatic acetic acids were extracted from wastewater samples using electromembrane extraction (EME). A thin layer of toluene immobilized on the walls of a polypropylene membrane envelope served as an artificial supported liquid membrane (SLM). The haloacetic acids (HAAs) (chloroacetic acid, dichloroacetic acid, and trifluoroacetic acid) and aromatic acetic acids (phenylacetic acid and p-hydroxyphenylacetic acid) were extracted through the SLM and into an alkalized aqueous buffer solution. The buffer solution was located inside the membrane envelope. The electrical potential difference sustained over the membrane acted as the driving force for the transport of haloacetic acids into the membrane by electrokinetic migration. After extraction, the extracts were analyzed by high-performance liquid chromatography-ultraviolet detection. The detection limits were between 0.072 and 40.3 ng L(-1). The calibration plot linearity was in the range of 5 and 200 µg L(-1) while the correlation coefficients for the analytes ranged from 0.9932 to 0.9967. Relative recoveries were in the range of 87-106%. The extraction efficiency was found to be comparable to that of solid-phase extraction.

Electromembrane extraction from biological fluids.

Electro-assisted extraction of ionic drugs from biological fluids through a supported liquid membrane (SLM) and into an aqueous acceptor solution was recently introduced as a new sample preparation technique termed electromembrane extraction (EME). The applied electrical potential across the SLM has typically been in the range of 1-300 V. Successful extractions have been demonstrated even with common batteries (9 V) instead of a power supply. The chemical composition of the SLM has been crucial for the selectivity and for the recoveries of the extraction. Compared to other liquid-phase microextraction techniques (LPME), extraction times have been reduced by a factor of 6-17, and successful extractions have been obtained at extraction times of 1-5 min, and even down to a few seconds with online microfluidic EME devices. The technique has provided very efficient sample clean-up and has been found well suited for the extraction of sample sizes in the low µL range. Extractions have been performed with both rod-shaped hydrophobic porous fibers and with flat hydrophobic porous sheets as SLM support. The technique has been successfully downscaled into the micro-chip format. The nature of the SLM has been tuned for extraction of drugs with different polarity allowing extractions to be tailored for specific applications depending on the analyte of interest. The technique has been found to be compatible with a wide range of biological fluids and extraction of drugs directly from untreated human plasma and whole blood has been demonstrated. EME selectively extracts the compounds from the complex biological sample matrix as well as allowing concentration of the drugs. With home-built equipment fully acceptable validation results have been obtained.

Determinants of cardiac vagal regulation: a cross-sectional study in a general population.

Attenuated cardiac vagal regulation indicates an increased risk of cardiac events, but the reasons for this impaired regulation are not well known. Cardiac vagal regulation was measured in 5.408 subjects (2627 men and 2781 women) who underwent short term (100s) ECG recordings during controlled deep respiration (0.1Hz). Under these conditions, the power in the low frequency (LF) spectral band (0.05 to 0.15Hz) predominantly reflects cardiac vagal outflow. There was a strong inverse relationship between LF power and age in both genders (ß=-0.033 in men and -0.035 in women; P<0.0005). There was a more rapid decline in women in the second and third decade in which LF power was significantly lower than in men (P=0.004). In both genders, there was an association between impaired cardiac vagal outflow and fibrinogen level. Altogether, the factors studied explained nearly 20% of the interindividual variation of LF power. In conclusion, in a general population, impaired cardiac vagal regulation is associated with many cardiovascular risk factors, including fibrinogen. Women have a more rapid decline of vagal regulation in the second and third decades.

Kinetic electro membrane extraction under stagnant conditions--fast isolation of drugs from untreated human plasma.

Amitriptyline, citalopram, fluoxetine, and fluvoxamine were isolated by electro membrane extraction (EME) from 70microl 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 30microl 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).

Simultaneous extraction of acidic and basic drugs at neutral sample pH: a novel electro-mediated microextraction approach.

The simultaneous extraction of acidic and basic analytes from a particular sample is a challenging task. In this work, electromembrane extraction (EME) of acidic non-steroidal anti-inflammatory drugs and basic ß-blockers in a single step was carried out for the first time. It was shown that by designing an appropriate compartmentalized membrane envelope, the two classes of drugs could be electrokinetically extracted by a 300 V direct current electrical potential. This method required only a very short 10-min extraction time from a pH-neutral sample, with a small amount (50 µL) of organic solvent (1-octanol) as the acceptor phase. Analysis was carried out using gas chromatography-mass spectrometry after derivatization of the analytes. Extraction parameters such as extraction time, applied voltage, pH range, and concentration of salt added were optimized. The proposed EME technique provided good linearity with correlation coefficients from 0.982 to 0.997 over a concentration range of 1-200 µg L⁻¹. Detection limits of the drugs ranged between 0.0081 and 0.26 µg L⁻¹, while reproducibility ranged from 6 to 13% (n=6). Finally, the application of the new method to wastewater samples was demonstrated.