Dispersive solid-phase extraction of racemic drugs using chiral ionic liquid-metal-organic framework composite sorbent.

Nowadays, enantioseparation of racemic pharmaceuticals in preparations is a prime concern by drug authorities across the globe. In the present work, it was attempted to develop novel enantioselective extraction method for five clinically used drugs (atenolol, propranolol, metoprolol, racecadotril, and raceanisodamine in their tablets) as racemates. The enantioselective solid-liquid extraction of these racemic drugs was carried out successfully by the use of chiral ionic liquid (CIL) in combination with a metal organic framework (MOF) for the first time. The composite CIL@MOF was synthesized from tropine based chiral ionic liquids with L-proline anion ([CnTr][L-Pro], n=3-6) and HKUST-1 type MOF, which was comprehensively characterized before being used as sorbent for enantioselective dispersive solid-liquid extraction. Preliminary selection of appropriate CIL was carried out on thin layer chromatography (TLC); under the joint participation of copper ion in the developing reagent, [C3Tr][L-Pro] ionic liquid showed better resolution performance with ΔRf value of 0.35 between the enantiomers was obtained for racemic atenolol. Moreover, the effect of copper salt dosage, amount of CIL, soli-liquid ratio and extraction time were investigated. The optimal conditions were obtained after thorough investigations; i.e. sample solution: ethanol, elution solvent: methanol, solid-liquid ratio: 12.5 mg:50 mL, amount of copper salt: 8 mg L-1, amount of impregnated CIL: 30% and extraction time of 30 min. As a result, enantiomeric excess values are 90.4%, 95%, 92%, 81.6% and 83.2% for atenolol, propranolol, metoprolol, racecadotril and raceanisodamine, respectively. The developed enantioselective method was validated following ICH guidelines and it was proved to be simple, effective and enantioselective way for separation of racemic pharmaceuticals with similar behaviors.

ß-Cyclodextrin Polymerized in Cross-Flowing Channels of Biomass Sawdust for Rapid and Highly Efficient Pharmaceutical Pollutants Removal from Water.

Water pollution arising from pharmaceuticals has raised great concerns about the potential risks for biosphere and human health. However, rapid and efficient removal of pharmaceutical contaminants from water remains challenging. Wood sawdust, a byproduct of the wood-processing industry, is an abundant, cost-effective, and sustainable material with a unique hierarchically porous microstructure. These features make wood sawdust quite interesting as a filtration material. Here, we report a novel cross-flow filtration composite based on ß-cyclodextrin-polymer-functionalized wood sawdust (ß-CD/WS) in which the pharmaceutical contaminant water flows through the sawn-off vessel channels and the micropores on the surface of the cell walls, generating the turbulence. Such water flow characteristics ensure full contact between pharmaceutical pollutants and ß-CD grafted on the cellulose backbone of wood sawdust, thereby enhancing the water treatment efficiency. Consequently, the ß-CD/WS filter device shows a high removal efficiency of over 97.5% within 90 s for various pharmaceutical contaminants including propranolol, amitriptyline, chlortetracycline, diclofenac, and levofloxacin, and a high saturation uptake capacity of 170, 156, 257, 159, and 185 mg g-1, respectively. The high-performance wood-sawdust-based cross-flow filtration opens new avenues for solving the global water pollution issues, especially those caused by pharmaceutical contaminants.

Separation of enantiomers of chiral basic drugs with amylose- and cellulose- phenylcarbamate-based chiral columns in acetonitrile and aqueous-acetonitrile in high-performance liquid chromatography with a focus on substituent electron-donor and electron-acceptor effects.

In this study, amylose- and cellulose-phenylcarbamate-based chiral columns with different chiral-selector (CS) chemistries were compared to each other for the separation of enantiomers of basic chiral analytes in acetonitrile and aqueous-acetonitrile mobile phases in HPLC. For two chemistries the amylose-based columns with coated and immobilized CSs were also compared. The comparison of CSs containing only electron-donating or electron-withdrawing substituents with those containing both electron-donating and electron-withdrawing substituents showed opposite results for the studied set of chiral analytes in the case of amylose and cellulose derivatives. Along with the chemistry of CS the focus was on the behavior of polysaccharide phenylcarbamates in acetonitrile versus aqueous acetonitrile as eluents. In agreement with earlier results, it was found that in contrast to the commonly accepted view, polysaccharide phenylcarbamates do not behave as typical reversed-phase materials for basic analytes either. In the range of water content in the mobile phase of up to 20-30% v/v the behavior of these CSs is similar to hydrophilic interaction liquid chromatography (HILIC)-type adsorbents. This means that with increasing water content in the mobile phase up to 20-30% v/v, the retention of analytes mostly decreases. The important finding of this study is that the separation efficiency improves for most analytes when switching from pure acetonitrile to aqueous acetonitrile. Therefore, in spite of reduced retention, the separation of enantiomers improves and thus, the HILIC-range of mobile phase composition, offering shorter analysis time and better peak resolution, is advantageous over pure polar-organic solvent mode. Interesting examples of enantiomer elution order (EEO) reversal were observed for some analytes based on the content of water in the mobile phase on Lux Cellulose-1 and Lux Amylose-2 columns.

Metal organic framework HKUST-1 modified with carboxymethyl-ß-cyclodextrin for use in improved open tubular capillary electrochromatographic enantioseparation of five basic drugs.

This work shows that the metal organic framework (MOF) HKUST-1 of type Cu3(BTC)2 (also referred to as MOF-199; a face-centered-cubic MOF containing nanochannels) is a most viable coating for use in enantioseparation in capillary electrochromatography (CEC). A HKUST-1 modified capillary was prepared and characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectra, elemental analysis and thermogravimetric analysis. CEC-based enantioseparation of the basic drugs propranolol (PRO), esmolol (ESM), metoprolol (MET), amlodipine (AML) and sotalol (SOT) was performed by using carboxymethyl-ß-cyclodextrin as the chiral selector. Compared with a fused-silica capillary, the resolutions are improved (ESM: 1.79; MET: 1.80; PRO: 4.35; SOT: 1.91; AML: 2.65). The concentration of chiral selector, buffer pH value, applied voltage and buffer concentration were optimized, and the reproducibilities of the migration times and Rs values were evaluated. Graphical abstract Schematic presentation of the preparation of a HKUST-1@capillary for enantioseparation of racemic drugs. Cu(NO3)2 and 1,3,5-benzenetricarboxylic acid (BTC) were utilized to prepare the HKUST-1@capillary. Then the capillary was applied to construct capillary electrochromatography system with carboxymethyl-ß-cyclodextrin (CM-ß-CD) for separation of basic racemic drugs.

Enantioseparation of propranolol, amlodipine and metoprolol by electrochromatography using an open tubular capillary modified with ß-cyclodextrin and poly(glycidyl methacrylate) nanoparticles.

The inner wall of a capillary was coated with glycidyl methacrylate (GMA) to form tentacle-type coating, and poly(glycidyl methacrylate) nanoparticles (PGMA NPs) were then immobilized on the film. Ethanediamine-ß-cyclodextrin as chiral selector was covalently bonded into the PGMA NPs through the ring-open reaction. The materials were characterized by SEM, TEM and FT-IR. The modified column was applied to the enantioseparation of the racemates of propranolol, amlodipine and metoprolol. Compared to a capillary with a single layer of CD-PGMA (without GMA coating) and to a CD-GMA system (without PGMA nanoparticles), the performance of the capillary is strongly improved. The effects of buffer pH value and applied voltage were optimized. Best resolutions (propranolol: 1.27, metoprolol: 1.01 and amlodipine: 2.93) were obtained when using the PGMA-coated capillary system. The run-to-run, day-to-day and column-to-column reproducibility were tested and found to be highly attractive. The new stationary phase is likely to have a large potential and scope in that it may also be applied to chiral separations of other enantiomers, such as amino acids and biogenic amines. Graphical abstract Schematic presentation of the preparation of a capillary column with glycidyl methacrylate (GMA) coating which was then immobilized with poly(glycidyl methacrylate) nanoparticles and ethanediamine-ß-cyclodextrin. This novel open tubular column was applied to construct capillary electrochromatography system for separation of basic racemic drugs.

Methods and approaches for determination and enantioseparation of (RS)-propranolol.

Propranolol, a ß-adrenergic receptor antagonist, is a chiral compound that is marketed as a racemate, but only the (S)-(-)-enantiomer is responsible for the ß-adrenoceptor blocking activity. Different chromatographic methods have been applied for separation and determination of enantiomers of (RS)-propranolol. In this article a review is presented on different liquid chromatographic methods used for enantioseparation of (RS)-propranolol, using both HPLC and TLC. In addition, some aspects of enantioseparation under achiral phases of liquid chromatography have been briefly mentioned.

Ultrasound-assisted heterogeneous activation of persulfate by nano zero-valent iron (nZVI) for the propranolol degradation in water.

This study investigated the degradation of propranolol (PRO), a beta (ß)-blockers, by nano zero-valent iron (nZVI) activated persulfate (PS) under ultrasonic irradiation. Effects of several critical factors were evaluated, inclusive of PS concentration, nZVI dosage, ultrasound power, initial pH, common anions, and chelating agent on PRO degradation kinetics. Higher PS concentration, nZVI dosage and ultrasound power as well as acidic pH favored the PRO degradation. Conversely, anions and chelating agent took on the inhibitory effect towards PRO degradation to different extents. Furthermore, the variations of morphology and surface composition of nZVI before and after the reaction were characterized by TEM, XRD and XPS. Finally, on the basis of identified degradation intermediates by LC/MS/MS analysis, this work tentatively proposed the degradation pathways. These encouraging results suggest that US/nZVI/PS process is a promising strategy for the treatment of PRO-induced water pollutant.

Magnetic multi-walled carbon nanotube poly(styrene-co-divinylbenzene) for propranolol extraction and separation by capillary electrophoresis.

AIM: The preparation of magnetic multi-walled carbon nanotube poly(styrene-co-divinylbenzene) for propranolol magnetic solid-phase extraction is described. MATERIALS & METHODS: A study comparing propranolol adsorption and desorption was performed with only magnetic multi-walled carbon nanotubes, and different poly(styrene-co-divinylbenzene) with and without magnetic multi-walled carbon nanotubes. Enantiomeric separation of propranolol took place by cyclodextrin-modified capillary electrophoresis and the method was validated in spiked human urine samples. RESULTS: Recovery values raised when styrene/divinylbenzene millimoles ratio was 19.57:15.80. Enrichment factors increased up to approximately 100, detection limits were 13.8 and 10.5 ng ml-1 for R- and S-propranolol respectively, quantitation limits were 46.0 and 34.8 ng ml-1 for R- and S-propranolol respectively, recoveries from spiked samples ranged from 90.9 to 109.0%, and relative standard deviations were <6.3%. CONCLUSION: This methodology was proven to be more effective than classical solid-phase extraction strategies and may be applied to other kind of biological samples.

Screening a small molecule library to identify inhibitors of NF-κB inducing kinase and pro-labor genes in human placenta.

The non-canonical NF-κB signaling (RelB/p52) pathway drives pro-labor genes in the human placenta, including corticotropin-releasing hormone (CRH) and cyclooxygenase-2 (COX-2), making this a potential therapeutic target to delay onset of labor. Here we sought to identify small molecule compounds from a pre-existing chemical library of orally active drugs that can inhibit this NF-κB signaling, and in turn, human placental CRH and COX-2 production. We used a cell-based assay coupled with a dual-luciferase reporter system to perform an in vitro screening of a small molecule library of 1,120 compounds for inhibition of the non-canonical NF-κB pathway. Cell toxicity studies and drug efflux transport MRP1 assays were used to further characterize the lead compounds. We have found that 14 drugs have selective inhibitory activity against lymphotoxin beta complex-induced activation of RelB/p52 in HEK293T cells, several of which also inhibited expression of CRH and COX-2 in human term trophoblast. We identified sulfapyridine and propranolol with activity against CRH and COX-2 that deserve further study. These drugs could serve as the basis for development of orally active drugs to affect length of gestation, first in an animal model, and then in clinical trials to prevent preterm birth during human pregnancy.

Studies of drug interactions with alpha1-acid glycoprotein by using on-line immunoextraction and high-performance affinity chromatography.

A method that combined on-line immunoextraction with high-performance affinity chromatography was developed to examine the binding of drugs with α1-acid glycoprotein (AGP). Affinity microcolumns containing immobilized polyclonal anti-AGP antibodies were developed that had a capture efficiency of up to 98.4% for AGP and a binding capacity of 0.72nmol AGP when using a 20mm×2.1mm i.d. microcolumn. These microcolumns were employed in various formats to examine the binding of drugs to normal AGP and AGP that had been adsorbed from serum samples for patients with systemic lupus erythematosus (SLE). Drugs that were screened in zonal elution experiments for their overall binding to these types of AGP included chlorpromazine, disopyramide, imipramine, propranolol, and warfarin. Most of these drugs showed an increase in their binding to the AGP from SLE serum when compared to normal AGP (i.e., an increase of 13-76%); however, disopyramide gave a 21-25% decrease in retention when the same AGP samples were compared. Frontal analysis was used to further evaluate the binding of disopyramide and imipramine to these forms of AGP. Both drugs gave a good fit to a model that involved a combination of saturable and non-saturable interactions with AGP. Changes in the non-saturable interactions accounted for most of variations seen in the binding of disopyramide and imipramine with the AGP samples. The methods used in this study could be adapted for use in personalized medicine and the study of other proteins or drugs using aqueous mixtures or clinical samples.

Determination of propranolol and carvedilol in urine samples using a magnetic polyamide composite and LC-MS/MS.

AIM: ß-blockers are compounds that bind with adrenoreceptors hindering their interaction with adrenalin and noradrenalin. They are clinically relevant and they are also used in some sport as doping agents. RESULTS: A new method based on the combination of dispersive micro-solid phase extraction and LC-MS/MS has been developed to determine propranolol and carvedilol in urine samples. For this purpose a magnetic-polyamide composite is synthesized and used as sorbent. Working under the optimum conditions, the method provides limits of detection and quantification in the range of 0.1-0.15 µg/l and 0.3-0.5 µg/l, for carvedilol and propranolol, respectively. The precision, expressed as RSD, was better than 9.6% and the relative recoveries varied between 73.7 and 81.3%. CONCLUSION: The methodology is appropriate for the determination of ß-blockers in urine samples at the low microgram per liter range for therapeutic purposes.

Application of rifampicin as a chiral selector for enantioresolution of basic drugs using capillary electrophoresis.

Rifampicin, a member of rifamycin sub-class of antibiotics which belongs to the naphthalenic ansamycin class of antibiotics, has a characteristic ansa structure, i.e., a ring structure or chromophore spanned by an aliphatic chain. The present work was designed to evaluate its potential as a chiral selector (CS) as its structure consisting of nine stereogenic centers, an aromatic moiety and several functional groups (i.e., one imine, one amide, one acetoxy residue, two aliphatic hydroxyl and three phenolic hydroxyl groups) was expected to instigate multiple enantioselective interactions, namely, hydrogen bonding and inclusion complexation with chiral analytes, and therefore resulting in efficient enantioseparations. Systematic experiments were performed to investigate the effects of concentration of CS, composition of background electrolyte (BGE) and applied voltage on chiral separation. Enantiomers of propranolol and metoprolol were baseline resolved using a BGE consisting of 20mM CS and 50/50 (v/v) iso-propanol/phosphate buffer (100mM, pH 7.0) whereas for enantiomers of sertraline, a BGE consisting of 23mM CS and 40/60 (v/v) iso-propanol/phosphate buffer (100mM, pH 7.0) resulted in baseline resolutions.

On-column entrapment of alpha1-acid glycoprotein for studies of drug-protein binding by high-performance affinity chromatography.

An on-column approach for protein entrapment was developed to immobilize alpha1-acid glycoprotein (AGP) for drug-protein binding studies based on high-performance affinity chromatography. Soluble AGP was physically entrapped by using microcolumns that contained hydrazide-activated porous silica and by employing mildly oxidized glycogen as a capping agent. Three on-column entrapment methods were evaluated and compared to a previous slurry-based entrapment method. The final selected method was used to prepare 1.0 cm × 2.1 mm I.D. affinity microcolumns that contained up to 21 (±4) µg AGP and that could be used over the course of more than 150 sample applications. Frontal analysis and zonal elution studies were performed on these affinity microcolumns to examine the binding of various drugs with the entrapped AGP. Site-selective competition studies were also conducted for these drugs. The results showed good agreement with previous observations for these drug-protein systems and with binding constants that have been reported in the literature. The entrapment method developed in this study should be useful for future work in the area of personalized medicine and in the high-throughput screening of drug interactions with AGP or other proteins. Graphical abstract On-column protein entrapment using a hydrazide-activated support and oxidized glycogen as a capping agent.

Liquid chromatographic enantioseparation of three beta-adrenolytics using new derivatizing reagents synthesized from (S)-ketoprofen and confirmation of configuration of diastereomers.

Diastereomers of racemic ß-adrenolytic drugs [namely (RS)-propranolol, (RS)-metoprolol and (RS)-atenolol] were synthesized under microwave irradiation with (S)-ketoprofen based chiral derivatization reagents (CDRs) newly synthesized for this purpose. (S)-Ketoprofen was chosen for its high molar absorptivity (εo ~ 40,000) and its availability as a pure (S)-enantiomer. Its -COOH group was activated with N-hydroxysuccinimide and N-hydroxybenzotriazole; these were easily introduced and also acted as good leaving groups during nucleophilic substitution by the amino group of the racemic ß-adrenolytics. The CDRs were characterized by UV, IR, 1 H-NMR, HRMS and CHNS. Separation of diastereomers was achieved by RP HPLC and open column chromatography. Absolute configuration of the diastereomers was established with the help of 1 HNMR supported by developing their optimized lowest energy structures using Gaussian 09 Rev. A.02 program and hybrid density functional B3LYP with 6-31G* basis set (based on density functional theory), and elution order was established. RP HPLC conditions for separation were optimized and the separation method was validated. The limit of detection values were 0.308 and 0.302 ng mL-1 . Copyright © 2016 John Wiley & Sons, Ltd.

Water-compatible graphene oxide/molecularly imprinted polymer coated stir bar sorptive extraction of propranolol from urine samples followed by high performance liquid chromatography-ultraviolet detection.

Due to the high selectivity and stability, molecularly imprinted polymers (MIPs) have been successfully applied in stir bar sorptive extraction (SBSE) as a special coating to improve the selective extraction capability for target analytes. However, traditional MIPs usually suffer from incompatibility in aqueous media and low adsorption capacity, which limit the application of MIP coated stir bar in aqueous samples. To solve these problems, a water-compatible graphene oxides (GO)/MIP composite coated stir bar was prepared in this work by in situ polymerization. The prepared water-compatible GO/MIP coated stir bar presented good mechanical strength and chemical stability, and its recognition ability in aqueous samples was improved due to the polymerization of MIP in water environment, the adsorption capacity for target analytes was also increased by the addition of GO in MIP pre-polymer solution. Based on it, a method of water-compatible GO/MIP coated stir bar sorptive extraction combined with high performance liquid chromatography-ultraviolet detector (HPLV-UV) was proposed for the analysis of propranolol (PRO) in aqueous solution. The influencing factors of SBSE, such as sample pH, salt effect, stirring rate, extraction time, desorption solvent and desorption time, were optimized, and the analytical performance of the developed SBSE-HPLC-UV method was evaluated under the optimized conditions. The limit of detection (LOD) of the proposed method for PRO was about 0.37 µg L(-1), and the enrichment factor (EF) was 59.7-fold (theoretical EF was 100-fold). The reproducibility was also investigated at concentrations of 5 µg L(-1) and the relative standard deviation (RSD) was found to be 7.3% (n=7). The proposed method of GO/MIP coating-SBSE-HPLC-UV was successfully applied for the assay of the interested PRO drug in urine samples, and further extended to the investigation of the excretion of the drugs by monitoring the variation of the concentration of PRO in urine within 10h after drug-taking.

(RS)-Propranolol: enantioseparation by HPLC using newly synthesized (S)-levofloxacin-based reagent, absolute configuration of diastereomers and recovery of native enantiomers by detagging.

Diastereomers of (RS)-propranolol were synthesized using (S)-levofloxacin-based new chiral derivatizing reagents (CDRs). Levofloxacin was chosen as the pure (S)-enantiomer for its high molar absorptivity (εo ∼ 24000) and availability at a low price. Its -COOH group had N-hydroxysuccinimide and N-hydroxybenzotriazole, which acted as good leaving groups during nucleophilic substitution by the amino group of the racemic (RS)-propranolol; the CDRs were characterized by UV, IR, (1) H-NMR, high resolution mass spectrometry (HRMS) and carbon, hydrogen, nitrogen, and sulphur fundamental elemental components analyser (CHNS). Diastereomers were separated quantitatively using open column chromatography; absolute configuration of the diastereomers was established and the reagent moiety was detagged under microwave-assisted acidic conditions. (S)- and (R)-propranolol as pure enantiomers and (S)-levofloxacin were separated, isolated and characterized. Optimized lowest-energy structures of the diastereomers were developed using Gaussian 09 Rev. A.02 program and hybrid density functional B3LYP with 6-31G* basis set (based on density functional theory) for explanation of elution order and configuration. In addition, RP HPLC conditions for separation of diastereomers were optimized with respect to pH, concentration of buffer, flow rate of mobile phase and nature of organic modifier. HPLC separation method was validated as per International Conference on Harmonization guidelines. With the systematic application of various analytical techniques, absolute configuration of the diastereomers (and the native enantiomers) of (RS)-propranolol was established. Copyright © 2016 John Wiley & Sons, Ltd.

Low environmental levels of neuro-active pharmaceuticals alter phototactic behaviour and reproduction in Daphnia magna.

Assessing the risks of emerging contaminants, such as pharmaceuticals in the environment requires an understanding of their exposure regime and their effects at environmentally relevant concentrations across species. Daphnia magna represents an excellent invertebrate model species to study the mode of action of emerging pollutants, allowing the assessment of effects at different biological levels. The present study aims to test the hypothesis that different families of neuro-active pharmaceuticals at low environmentally relevant concentrations may lead to similar phenotypic responses in D. magna. Phenotypic traits included reproduction and behavioural responses. Selected pharmaceuticals were carbamazepine, diazepam and propranolol, three widely prescribed compounds, already detected at considerable levels in the environment (ng to few µg/L). Fluoxetine was also included in behavioural assays. The three tested neuro-active pharmaceuticals were able to enhance reproduction at 1ng/L of propranolol, 0.1µg/L of diazepam and 1µg/L of carbamazepine. Fluoxetine, carbamazepine and diazepam increased positive phototactic behaviour at concentrations ranging from 1, 10 and 100ng/L, respectively. Reported responses were nonmonotonic, which means that eco-toxicity testing of pharmaceuticals need to assess effects at the ng/L range.

Determination of enantiomers by FESI-sweeping with an acid-labile sweeper in nonaqueous capillary electrophoresis.

In this work, a facile and highly efficient on-line concentration strategy based on a coupling of field enhanced sample injection (FESI) and sweeping was developed for the determination of trace enantiomers (propranolol, PL) by nonaqueous capillary electrophoresis (NACE). In this FESI-sweeping method, the use of a sample of high acidity and low conductivity (pH* = 2.5, 4.0 µS cm(-1)) allowed for a large amount of analyte injection. Then, the concentration of the analytes was carried out by sweeping based on the interaction of an acid-labile anionic selector, di-n-butyl L-tartrate-boric acid complex acid, and cationic analytes. Simultaneously, the concentrated analytes were released and focused at the boundary of the acid sample solution and separation buffer due to the decomposition of the selector in the acid sample solution. Under the optimum conditions, a 21,000-fold sensitivity enhancement upon normal capillary zone electrophoresis (CZE) was achieved for PL enantiomers. The detection limits of R-propranolol and S-propranolol were 0.26 ng mL(-1) and 0.31 ng mL(-1), respectively. Eventually, the FESI-sweeping method was applied to detect PL enantiomers in plasma, saliva, and urine.

Thermodynamic studies for adsorption of ionizable pharmaceuticals onto soil.

Although pharmaceutical compounds (PCs) are being used more and more widely, and studies have been carried out to assess their presence in the environment, knowledge of their fate and behavior, especially under different environmental conditions, is still limited. The principle objective of the present work, therefore, is to evaluate the adsorption behavior of three ionizable, polar compounds occurring in different forms: cationic (propranolol - PRO), anionic (sulfisoxazole - SSX) and neutral (sulfaguanidine - SGD) onto soil under various temperature conditions. The adsorption thermodynamics of these researched compounds were extensively investigated using parameters such as enthalpy change (ΔH°), Gibbs free energy change (ΔG°) as well as entropy change (ΔS°). These calculations reveal that sorption of PRO is exothermic, spontaneous and enthalpy driven, sorption of SGD is endothermic, spontaneous and entropy driven whereas sorption of SSX is endothermic, spontaneous only above the temperature of 303.15K and entropy driven. Furthermore, we submit that the calculated values yield valuable information regarding the sorption mechanism of PRO, SGD and SSX onto soils.

Electrically assisted liquid-phase microextraction combined with capillary electrophoresis for quantification of propranolol enantiomers in human body fluids.

In this study, electromembrane extraction (EME) combined with cyclodextrin (CD)-modified capillary electrophoresis (CE) was applied for the extraction, separation, and quantification of propranolol (PRO) enantiomers from biological samples. The PRO enantiomers were extracted from aqueous donor solutions, through a supported liquid membrane (SLM) consisting of 2-nitrophenyl octyl ether (NPOE) impregnated on the wall of the hollow fiber, and into a 20-µL acidic aqueous acceptor solution into the lumen of hollow fiber. Important parameters affecting EME efficiency such as extraction voltage, extraction time, pH of the donor and acceptor solutions were optimized using a Box-Behnken design (BBD). Then, under these optimized conditions, the acceptor solution was analyzed using an optimized CD-modified CE. Several types of CD were evaluated and best results were obtained using a fused-silica capillary with ammonium acetate (80 mM, pH 2.5) containing 8 mM hydroxypropyl-ß-CD as a chiral selector, applied voltage of 18 kV, and temperature of 20°C. The relative recoveries were obtained in the range of 78-95%. Finally, the performance of the present method was evaluated for the extraction and determination of PRO enantiomers in real biological samples.