In this work, the solid-liquid equilibrium (SLE) of four binary systems combining two active pharmaceutical ingredients (APIs) capable of forming co-amorphous systems (CAMs) was investigated. The binary systems studied were naproxen-indomethacin, naproxen-ibuprofen, naproxen-probucol, and indomethacin-paracetamol. The SLE was experimentally determined by differential scanning calorimetry. The thermograms obtained revealed that all binary mixtures investigated form eutectic systems. Melting of the initial binary crystalline mixtures and subsequent quenching lead to the formation of CAM for all binary systems and most of the compositions studied. The experimentally obtained liquidus and eutectic temperatures were compared to theoretical predictions using the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state and conductor-like screening model for real solvents (COSMO-RS), as implemented in the Amsterdam Modeling Suite (COSMO-RS-AMS). On the basis of the obtained results, the ability of these models to predict the phase diagrams for the investigated API-API binary systems was evaluated. Furthermore, the glass transition temperature (Tg) of naproxen (NAP), a compound with a high tendency to recrystallize, whose literature values are considerably scattered, was newly determined by measuring and modeling the Tg values of binary mixtures in which amorphous NAP was stabilized. Based on this analysis, erroneous literature values were identified.

• Klíčová slova
• COSMO-RS, PC-SAFT, active pharmaceutical ingredients, co-amorphous systems, glass transition temperature, phase diagrams, physical stability, solid–liquid equilibrium,
• Publikační typ
• časopisecké články MeSH

A new extraction technique based on the off-line combination of pressurized-liquid with solid-phase extraction (PLE-SPE) is described. The method was used for the extraction of bioactive phenolic acids (protocatechuic, p-hydroxybenzoic, 2,3-dihydroxybenzoic, chlorogenic, vanillic, caffeic, p-coumaric, salicylic acid), cinnamic acid and hydroxybenzaldehydes (p-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, vanillin) from in vitro culture of two freshwater algae (Anabaena doliolum and Spongiochloris spongiosa) and from food products of marine macroalgae Porphyra tenera (nori) and Undaria pinnatifida (wakame). For the identification and quantification of the compounds the molecular ions [M-H](-) and specific fragments were analyzed by quadrupole mass spectrometry analyzer connected on-line with a reversed-phase HPLC system. Our analysis showed that the freshwater algae and marine algal products contained submicrogram or microgram level of above-mentioned phenols per gram of lyophilized sample. In addition, the total phenol content (Folin-Ciocalteu assay) and antioxidant activity (TEAC assay, Trolox equivalent antioxidant capacity assay) of the PLE-SPE extracts were determined and discussed.

• MeSH
• antioxidancia analýza   chemie   MeSH
• biologie sladkých vod metody   MeSH
• cinnamáty analýza   chemie   MeSH
• Eukaryota chemie   MeSH
• extrakce na pevné fázi metody   MeSH
• fenoly analýza   chemie   MeSH
• kyselina benzoová analýza   chemie   MeSH
• mořská voda chemie   MeSH
• on-line systémy * MeSH
• referenční standardy MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antioxidancia MeSH
• cinnamáty MeSH
• cinnamic acid MeSH Prohlížeč
• fenoly MeSH
• kyselina benzoová MeSH

A double-stage Lab-In-Syringe automated extraction procedure coupled online to HPLC for the determination of four sulfonamides in urine has been developed. Our method is based on homogeneous liquid-liquid extraction at pH 3 using water-miscible acetonitrile with induction of phase separation by the addition of a saturated solution of kosmotropic salts MgSO4 and NaCl. The procedure allowed extraction of the moderately polar model analytes and the use of a solvent that is compatible with the used separation technique. The automated sample preparation system based on the stirring-assisted Lab-In-Syringe approach was coupled on-line with HPLC-UV for the subsequent separation of the sulfonamide antibiotics. To improve both preconcentration factor and extract cleanup, the analytes were trapped at pH 10 in an anion-exchange resin cartridge integrated into the HPLC injection loop thus achieving a double-stage sample clean-up. Analytes were eluted using an acidic HPLC mobile phase in gradient elution mode. Running the analytes separation and the two-step preparation of the following sample in parallel reduced the total time of analysis to mere 13.5 min. Limits of detection ranged from 5.0 to 7.5 μg/L with linear working ranges of 50-5000 μg/L (r2 > 0.9997) and RSD ≤ 5% (n = 6) at a concentration level of 50 μg/L. Average recovery values were 102.7 ± 7.4% after spiking of urine with sulfonamides at concentrations of 2.5 and 5 mg/L followed by 5 times dilution. To the best of our knowledge, the use of Lab-In-Syringe for the automation of coupled homogeneous liquid-liquid extraction and SPE for preparation of the complex matrices suitable for separation techniques is here presented for the first time.

• Klíčová slova
• Homogeneous liquid-liquid extraction, Lab-in-syringe, Online solid-phase extraction, Salting-out, Sulfonamides, Urine,
• MeSH
• antibakteriální látky * analýza   MeSH
• chlorid sodný * MeSH
• extrakce kapalina-kapalina MeSH
• extrakce na pevné fázi MeSH
• injekční stříkačky MeSH
• sulfonamidy MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• chlorid sodný * MeSH
• sulfonamidy MeSH

In this work, an on-line SPE-HPLC method with spectrophotometric detection was developed for the determination of coumarins in complex samples. For the on-line cleanup of samples, a molecularly imprinted polymer was packed into the column cartridge and coupled directly with HPLC (MISPE-HPLC) using a column switching system. The separation of coumarins was performed on a C18 core-shell column (100×4.6mm, 5μm) with a mobile phase consisting of 0.3% acetic acid/acetonitrile with gradient elution at a flow-rate of 1mLmin-1. The total time of the whole analytical run, including the extraction step, was 13.25min. The on-line MISPE-HPLC method was optimized and validated. The results showed good linearity (0.10-100μgmL-1) with correlation coefficients higher than 0.99. The LOD values were from 0.03 to 0.15μgmL-1. The proposed method was successfully applied for analysis of real samples (Cassia cinnamon, chamomile tea, and Tokaj specialty wines) and obtained recoveries varied from 78.7% to 112.2% with an RSD less than 9%.

• Klíčová slova
• Chromatography, Column switching system, Coumarins, Molecularly imprinted polymers, On-line solid phase extraction,
• MeSH
• extrakce na pevné fázi * MeSH
• kumariny MeSH
• molekulový imprinting MeSH
• on-line systémy MeSH
• polymery MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kumariny MeSH
• polymery MeSH

Porous polymer monoliths have been used to develop an online solid-phase extraction with liquid chromatography method for determination of dopamine in urine as well as for a continuous monitoring of dopamine in flowing system. A polymerization mixture containing 4-vinylphenylboronic acid monomer has been used to prepare a trapping column based on specific ring formation reaction with dopamine cis-diol functionality. Additionally, a monolithic stationary phase with zwitterion functionality has been used to prepare capillary column for the separation of dopamine. Experimental conditions including molarity, pH, and flow rate of the loading buffer together with a valve switching time have been optimized to provide the highest recovery for dopamine. Experimental setup has been used to determine dopamine in a urine. By using both calibration curve and standard addition method, the dopamine level was determined to be 1.19 and 1.28 mg/L, respectively. Further, we have used experimental design to optimize coupling of two extraction monolithic loops to separation capillary column with monolithic phase for a comprehensive monitoring of dopamine. After multivariate analysis, sample loading flow-rate and a flow-rate of flushing buffer were selected as the most significant variables. Optimized experimental setup was applied to continuously monitor dopamine degradation.

• Klíčová slova
• Design of experiments, Dopamine, Monomers, Polymer monoliths, Solid-phase extraction,
• MeSH
• dopamin moč   MeSH
• extrakce na pevné fázi * MeSH
• lidé MeSH
• polymerizace MeSH
• polymery MeSH
• vysokoúčinná kapalinová chromatografie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dopamin MeSH
• polymery MeSH

Reaching trace amounts of mycotoxin contamination requires sensitive and selective analytical tools for their determination. Improving the selectivity of sample pretreatment steps covering new and modern extraction techniques is one way to achieve it. Molecularly imprinted polymers as selective sorbent for extraction undoubtedly meet these criteria. The presented work is focused on the hyphenation of on-line molecularly imprinted solid-phase extraction with a chromatography system using a column-switching approach. Making a critical comparison with a simultaneously developed off-line extraction procedure, evaluation of pros and cons of each method, and determining the reliability of both methods on a real sample analysis were carried out. Both high-performance liquid chromatography methods, using off-line extraction on molecularly imprinted polymer and an on-line column-switching approach, were validated, and the validation results were compared against each other. Although automation leads to significant time savings, fewer human errors, and required no handling of toxic solvents, it reached worse detection limits (15 versus 6 μg/L), worse recovery values (68.3-123.5 versus 81.2-109.9%), and worse efficiency throughout the entire clean-up process in comparison with the off-line extraction method. The difficulties encountered, the compromises made during the optimization of on-line coupling and their critical evaluation are presented in detail.

• Klíčová slova
• column-switching chromatography, molecularly imprinted polymers, mycotoxin, on-line solid-phase extraction, patulin,
• MeSH
• extrakce na pevné fázi * MeSH
• molekulový imprinting * MeSH
• patulin izolace a purifikace   MeSH
• polymery MeSH
• reprodukovatelnost výsledků MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• patulin MeSH
• polymery MeSH

Zanamivir (Za) is a highly polar and hydrophilic antiviral drug used for the treatment of influenza A viruses. Za has been detected in rivers of Japan and it's environmental occurrence has the risk of inducing antiviral resistant avian influenza viruses. In this study, a rapid automated online solid phase extraction liquid chromatography method using bonded zwitterionic stationary phases and tandem mass spectrometry (SPE/LC-MS/MS) for trace analysis of Za was developed. Furthermore, an internal standard (IS) calibration method capable of quantifying Za in Milli-Q, surface water, sewage effluent and sewage influent was evaluated. Optimum pre-extraction sample composition was found to be 95/5 v/v acetonitrile/water sample and 1% formic acid. The developed method showed acceptable linearities (r(2)≥0.994), filtration recovery (≥91%), and intra-day precisions (RSD≤16%), and acceptable and environmentally relevant LOQs (≤20ngL(-1)). Storage tests showed no significant losses of Za during 20 days and +4/-20°C (≤12%) with the exception of influent samples, which should be kept at -20°C to avoid significant Za losses. The applicability of the method was demonstrated in a study on phototransformation of Za in unfiltered and filtered surface water during 28 days of artificial UV irradiation exposure. No significant (≤12%) phototransformation was found in surface water after 28 days suggesting a relatively high photostability of Za and that Za should be of environmental concern.

• Klíčová slova
• Antivirals, Liquid chromatography, Online solid phase extraction, Tandem mass spectrometry, ZIC-HILIC, Zanamivir,
• MeSH
• acetonitrily chemie   MeSH
• antivirové látky analýza   chemie   MeSH
• chemické látky znečišťující vodu analýza   chemie   MeSH
• chromatografie kapalinová metody   MeSH
• extrakce na pevné fázi metody   MeSH
• formiáty chemie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• on-line systémy MeSH
• řeky chemie   MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• ultrafialové záření MeSH
• zanamivir analýza   chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Japonsko MeSH
• Názvy látek
• acetonitrile MeSH Prohlížeč
• acetonitrily MeSH
• antivirové látky MeSH
• chemické látky znečišťující vodu MeSH
• formiáty MeSH
• formic acid MeSH Prohlížeč
• zanamivir MeSH

Simulation techniques based on accurate and efficient representations of potential energy surfaces are urgently needed for the understanding of complex systems such as solid-liquid interfaces. Here we present a machine learning framework that enables the efficient development and validation of models for complex aqueous systems. Instead of trying to deliver a globally optimal machine learning potential, we propose to develop models applicable to specific thermodynamic state points in a simple and user-friendly process. After an initial ab initio simulation, a machine learning potential is constructed with minimum human effort through a data-driven active learning protocol. Such models can afterward be applied in exhaustive simulations to provide reliable answers for the scientific question at hand or to systematically explore the thermal performance of ab initio methods. We showcase this methodology on a diverse set of aqueous systems comprising bulk water with different ions in solution, water on a titanium dioxide surface, and water confined in nanotubes and between molybdenum disulfide sheets. Highlighting the accuracy of our approach with respect to the underlying ab initio reference, the resulting models are evaluated in detail with an automated validation protocol that includes structural and dynamical properties and the precision of the force prediction of the models. Finally, we demonstrate the capabilities of our approach for the description of water on the rutile titanium dioxide (110) surface to analyze the structure and mobility of water on this surface. Such machine learning models provide a straightforward and uncomplicated but accurate extension of simulation time and length scales for complex systems.

• Klíčová slova
• aqueous phase, machine learning potentials, solid–liquid systems,
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

A new selective molecularly imprinted polymer has been prepared and used for extraction in on-line SPE-HPLC to achieve the selective determination of citrinin. Four different imprinted polymers varying in combinations of components were prepared by bulk polymerization and evaluated in terms of binding capacity and selectivity. Imprinted polymer prepared from a mixture comprising 1-hydoxy-2-naphtoic acid as the template molecule, acrylamide as the structural monomer, ethylene dimethacrylate as the cross-linker (in a molar ratio of 1:4:16), and acetonitrile as the porogenic solvent exhibited the best properties. The selectivity of this sorbent was confirmed by comparison with the non-imprinted counterpart prepared using the same polymerization carried out in the absence of template. Imprinted polymer was packed in a 20 × 3 mm i.d. steel cartridge and coupled to the on-line SPE-HPLC system through a six-port switching valve. The method for determination of citrinin including the on-line extraction step was then developed and validated. The sample in the form of methanolic extract was loaded, cleaned, and preconcentrated in the imprinted SPE cartridge. Subsequent separation of citrinin from residual interferences was achieved using the analytical column Kinetex Biphenyl 100 × 4.6 mm i.d., 5 μm particle size, and fluorescence detection (Ex 335, Em 500 nm). The total analysis time was only 9.50 min. Our fully validated method was also applied to analysis of food supplements based on red yeast rice extracts, the control of which is implemented in European legislation. Only minor yet acceptable contamination was found in tested samples.

• Klíčová slova
• Citrinin, Liquid chromatography, Molecularly imprinted polymer, Mycotoxin, On-line solid-phase extraction, Red yeast rice extracts,
• Publikační typ
• časopisecké články MeSH

In the present paper a new extraction technique based on the combination of solid-phase/supercritical-fluid extraction (SPE/SFE) with subsequent reversed-phase HPLC is described. The SPE/SFE extractor was originally constructed from SPE-cartridge incorporated into the SFE extraction cell. Selected groups of benzoic acid derivatives (p-hydroxybenzoic, protocatechuic, gallic, vanillic and syringic acid), hydroxybenzaldehydes (4-hydroxybenzaldehyde and 3,4-dihydroxybenzaldehyde) and cinnamic acid derivatives (o-coumaric, p-coumaric, caffeic, ferulic, sinapic and chlorogenic acid) were extracted. Cyclic addition of binary extraction solvent system based on methanol:water (1:1, v/v) and methanol/ammonia aqueous solution was used for extraction at 40MPa and 80 degrees C. The p-hydroxybenzoic, protocatechuic, vanillic, syringic, caffeic and chlorogenic acid; 4-hydroxybenzaldehyde and 3,4-dihydroxybenzaldehyde were identified by HPLC-electrospray mass spectrometry in SPE/SFE extracts of acid hydrolyzates of microalga (Spongiochloris spongiosa) and cyanobacterial strains (Spirulina platensis, Anabaena doliolum, Nostoc sp., and Cylindrospermum sp.). For the identification and quantification of the compounds the quasi-molecular ions [M-H](-) and specific fragments were analysed by quadrupole mass spectrometry analyzer. Our analysis showed that the microalgae and cyanobacteria usually contained phenolic acids or aldehydes at microg levels per gram of lyophilized sample. The proposed SPE/SFE extraction method would be useful for the analysis of different plant species containing trace amount of polar fraction of phenols.

• MeSH
• aldehydy analýza   chemie   MeSH
• Chlorophyta chemie   MeSH
• design vybavení MeSH
• extrakce na pevné fázi metody   MeSH
• fenoly analýza   chemie   MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
• kinetika MeSH
• methanol chemie   MeSH
• reprodukovatelnost výsledků MeSH
• sinice chemie   MeSH
• teplota MeSH
• tlak MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aldehydy MeSH
• fenoly MeSH
• methanol MeSH