Fast Screening of Whole Blood Samples and Pharmaceutical Compounds for Enantiorecognition of Free L-T3 , L-T4 , and D-T4.

A fast screening method of whole blood was proposed for enantiorecognition of free L-T3 , L-T4 , and D-T4 . Stochastic microsensors based on four inulins (IN, IQ, TEX, and HD) immobilized on diamond paste (DP) were used for recognition of free L-T3 , L-T4 , and D-T4 . For the enantiorecognition of free L-T4 and D-T4 in whole blood and pharmaceutical samples, the best microsensor was the one based on TEX/DP (wide linear concentration ranges, and low limits of quantification). The best limit of detection for the assay of free L-T3 (400 fmol/L) was recorded using the microsensors based on HD/DP, while for the assay of free L-T4, and D-T4 the best limit of determination (1 pmol/L) was recorded using the TX/DP-based microsensor. For the enantiorecognition of free L-T3 in whole blood and pharmaceutical samples the best microsensor was the one based on HD/DP (the wider linear concentration range, and the lower limit of quantification - of pmol/L magnitude order). For the enantiorecognition of free L-T3 in whole blood and pharmaceutical samples the best microsensor was the one based on HD/DP (the wider linear concentration range, and the lower limit of quantification - of pmol/L magnitude order). Free L-T3 , L-T4 , and D-T4 were recovered with high reliabilities in whole blood samples (recoveries higher than 99.00%, with RSD values lower than 1.00%) and pharmaceutical samples (recoveries higher than 95.00% with RSD values lower than 1.00%).

Hydrophobicity-aided potentiometric detection of catecholamines, beta-agonists, and beta-blockers in a mixed-solvent capillary electrophoresis system.

A series of cationic drug-like substances with distinct basicity, hydrogen-bonding ability, and hydrophobicity, including three catecholamines, two beta-agonists, and thirteen beta-blockers, was successfully detected in a capillary electrophoresis system using an end-capillary coupled potentiometric sensor consisting of a PVC-based liquid membrane deposited directly on a 100 mum diameter copper rod. The electrophoretic separation was performed on a 72 cm x 75 microm id uncoated fused-silica capillary with an acidic background electrolyte containing phosphoric acid in a water-acetonitrile mixture, pH* 2.8. Samples were injected electrokinetically at 5.0 kV for 10 s and a running voltage of 19.5 kV was applied. Excluding the bufuralol/practolol pair, baseline separation of all substances was achieved in the developed CE system within 9 minutes. A linear relationship (R(2) 0.8752) between the sensitivity of the applied potentiometric detector and the parameter log P characterising the hydrophobicity of the analytes was demonstrated. The best observable limits of detection (LODs) were obtained for the highly hydrophobic substances, i. e. bufuralol (8.10 x 10(-8) M injected concentration, S/N = 3), propranolol, alprenolol, and clenbuterol (ca. 1.10 x 10(-7) M). In the case of hydrophilic catecholamines and carbuterol their LODs with potentiometric detection were lowered by a factor of almost one thousand, reaching a value of 6.6 x 10(-5) M.

Unique potentiometric detection systems for HPLC determination of some steroids in human urine.

Isocratic HPLC with potentiometric detection is used for the determination of some 17-ketosteroids (17-KS), e.g., androsterone, dehydroepiandrosterone and estrone, and their respective sulfated conjugates (17-KSS). Glassy carbon or composite electrodes containing a mixture of graphite and poly(vinyl chloride), PVC, were used as substrate electrodes. These substrates were covered either by montmorillonite or potassium tetrakis(p-chlorophenyl) borate containing PVC-based rubber phase membranes. The neutral 17-KS compounds were derivatized with Girard's reagent P (GP) to obtain cationic pyridinium acetohydrazones prior to the HPLC/potentiometric detection assay. No side reactions were observed, and the GP itself was not interfering. The method yielded accurate and reproducible results and was applicable to samples containing down to micromolar concentrations. Next, the 17-KSS compounds, acting as anionic charged molecules, were determined directly in human urine samples with the HPLC/potentiometry combination without preliminary derivatization. For this purpose, a new anion-sensitive potentiometric electrode was developed using a macrocyclic polyamine containing, PVC-based, rubber phase membrane. The three 17-KSS compounds were also determined accurately down to micromolar concentrations. Especially, the main androgen metabolites as dehydroepiandrosterone sulfate and androsterone sulfate could be selectively determined with a developed potentiometric sensor in human urine samples without time-consuming cleanup and preconcentration step.

Advantageous Extraction, Cleanup, and UHPLC-MS/MS Detection of Patulin Mycotoxin in Dietary Supplements and Herbal Blends Containing Hawberry from Crataegus spp.

Patulin (PAT) is a highly genotoxic mycotoxin still found as the common contaminant of various kinds of spoiled fruits and related commodities which are often endorsed as the health-enhancing products. Thus, a fast and convenient liquid-solid extraction followed by a solid-phase cleanup with the MycoSep®228 AflaPat multifunctional column was used for the highly efficient isolation of PAT with an average recovery of 112.7% from commercial dietary supplements and herbal blends formulated with dried hawberry. Analysis of the PAT content was carried out using gradient elution with a Synergi Polar C18 column (150 × 2 mm, 4 µm) and UHPLC system equipped with a mass spectrometer. PAT was detected in all (n=14) commercial single-component dietary supplements formulated with dried hawberry belonging to Crataegus monogyna and/or Crataegus laevigata. Similarly, PAT was detected in 67% of the studied multicomponent commercial herbal blends (n=6) that contained-in addition to hawberry-different amounts of apple, chokeberry, elderberry, hibiscus, or mallow. Moreover, the PAT content was determined in the hawberry collected from the mature wild hawthorn trees belonging to three botanical species, Crataegus monogyna Jacq., Crataegus laevigata (Poiret) DC, and Crataegus rhipidophylla Gand, growing in the recreational forest areas and in the law-protected state national forest park in Poland. In conclusion, to prevent PAT accumulation and reduce the health risk of consumers in globalizing markets, the implementation of improved cultivation/processing practices of hawthorn trees and hawberry as well as increased analytical control related to the presence of PAT in dietary supplements and herbal blends formulated with fresh, dried, or frozen hawberry should be urgently recommended.

Supramolecular chiro-biomedical assays and enantioselective HPLC analyses for evaluation of profens as non-steroidal anti-inflammatory drugs, potential anticancer agents and common xenobiotics.

The permanent world-wide increase in therapeutic administration of racemic profens as easy available non-prescribed analgesic drugs and a common first-choice anti-inflammatory agents was recently linked with renewed interest in their beneficial use, also as enantiopure formulations, to treat and/or prevent a variety of human malignancies including its four major types as colorectal, breast, lung, and prostate cancer. This underlies the continuous need of selecting perfectly suited chiral separation methods of profens capable to determine nanolevels of a distomer in presence of the eutomer in a variety of complex biological and environmental media. Thus, current improvements for direct enantiomeric separations of profens by well defined supramolecular-based chiral HPLC and recently developed monolithic, combinatorial, bimodal and polymeric chiral stationary phases employing a modern supramolecular chirality concepts has been outlined in this review. The use of diverse supramolecular approaches for chiral HPLC as an easy accessible tool enabling fast development of nanoscale enantioselective, high-throughput and gradient screening procedures for in situ monitoring of stereoselective ADME properties of profens in range of anticancer drug discovery technologies has been also addressed.

Diversity oriented high-throughput screening of 1,3,4-oxadiazole modified chlorophenylureas and halogenobenzamides by HPLC with peptidomimetic calixarene-bonded stationary phases.

Retention profiles in series of the neutral and highly hydrophobic 1,3,4-oxadiazoles containing chlorophenylurea and halogenobenzamide moiety and indicating analgesic activity were determined in the isocratic standard- and narrow-bore HPLC systems employing, respectively, various octadecylsilica and different calixarene bonded stationary phases. When acetonitrile - 2.65 mM phosphoric acid (55 : 45, %, v/v), pH* 3.25, mobile phase was applied retention of these compounds increased with decline of their overall hydrophobicity according to the general preference of more polar compounds by calixarene cavity in time of its non-specific host-guest supramolecular interactions with halogenated substances. The size of calixarene nanocavity and its upper-rim substitution did not change the observed retention order, resolution and selectivity of separation for oxadiazoles. Compared to the retention on the non-end-capped and the highly-end-capped octadecylsilica HPLC column a most improved separation of some regioisomers of halogenated 1,3,4-oxadiazoles were observed on both used calixarene-type HPLC supports. In addition, preliminary data on the self-assembled supramolecular crystal structure of exemplary 1,3,4-oxadiazolchlorophenylurea with cis-elongated conformation was reported and formation of the monovalent inclusion host-guest complexes between 1,3,4-oxadiazoles and each calixarene-type stationary phase was studied with molecular modelling MM+ and AM1 methods. The structural, isomeric and energetic factors leading to the hydrogen bond stabilized inclusion complexes between these species were considered and used for explanation of observed retention sequence and selectivity of 1,3,4-oxadiazoles separation in applied calixarene-based HPLC systems. All these data would be useful in future development of optimized procedures enabling encapsulation of 1,3,4-oxadiazolurea-type drugs with calixarenes.

Supramolecular systems-based HPLC for chiral separation of beta-adrenergics and beta-adrenolytics in drug discovery schemes.

Increasing amount of data considering polymorphism, splice variants and various affinity states of beta-adrenoceptors has resulted in a new range of opportunities for enantiopure beta-adrenergic and beta-adrenolytic drug discovery and continuous development of reliable high-throughput screening procedures enabling tissue specific pharmacological evaluation of these drugs. Design and fast pharmacological profiling of single enantiomeric molecules combining beta-adrenoceptor affinity with other pharmacophores is also still challenging ability. As the use of chiral stationary phases in HPLC has particularly benefited from results of supramolecular chemistry, this review summarises recent achievements provided by this technique in deciphering of enatiorecognition phenomena affecting pharmacological selectivity of beta-adrenergics and beta-adrenolytics and modifying the efficiency of currently proposed beta-adrenoceptor-targeted therapies. Detailed characteristic of chiral separation performance of these drugs in the range of available supramolecular HPLC systems has also been presented.

[Viability of murine 3T3 fibroblasts on the poly(methyl methacrylate) surface modified by constant UV irradiation]. / Przezywalnosc fibroblastów 3T3 na powierzchni poli(metakrylanu metylu) modyfikowanego promieniowaniem UV.

Poly(methyl methacrylate) (PMMA) is commonly applied both in dentistry (bone cement) and in ophthalmology (contact lens, intraocular implants). High adhesion of fibroblasts to bone cement is desirable but keratoprosthesis (intraocular lens--IOL) should be characterized by good transparency and indicate no cells adhesion. Some earlier reports show that sterilization and modification of surface properties of some polymers can be achieved by UV-irradiation which causes a serious physicochemical change in polymer materials to depth of 4 microm. In present studies the surface of PMMA films (30 microm) was continuously irradiated with monochromatic UV-light at 254 nm in varied time intervals. The viability of murine 3T3 fibroblasts cultivated by 12 hours on the surfaces of the non-exposed and the UV-irradiated PMMA in relation to the control fibroblast cell line cultured on the surface of borosilicate glass was estimated with standard fluorescence microscopy procedure. It was found, that 3T3 fibroblasts are highly sensitive to the chemical changes of irradiated surface of PMMA, i.e. increase of surface hydrophilicity and oxidation degree accompanied by decrease of polymer molecular mass and increase of free monomer fraction as determined on the results of contact angle measurements and attenuated total reflection infrared spectra. The percentage of living 3T3 fibroblast cells was 87% after cultivation on the untreated virgine PMMA and only 47% after cultivation on the polymer which was pre-irradiated by 72 h. No further changes in fibroblasts viability (47%) was observed in cultures developed on PMMA after 96 h of its introductory permanent irradiation. However, a period of 48 h of such constant UV-irradiation was quite optimal to obtain a specific modification of PMMA surface leading to significantly increased viability of cultured 3T3 fibroblasts up to the 94%.

Residental factors affecting nutrient intake and nutritional status of female pharmacy students in Bydgoszcz.

The aim of present study was to estimate nutrient intake as well as nutritional status of female pharmacy students from Bydgoszcz, and to investigate relationship of these factors with type of usual residence place during academic year The 24-hour recall method was used to evaluate dietary intake of 47 subjects. Measured values of height, body mass and four skinfolds thickness were used for calculation of BM, FFM, %FM indices. An analysis of nutritional status of studied population showed lower body mass and BMI in the sub-group of female students residing outside of their family home. In comparison to the female students living without parents percentage of energy provided by total fat (29.9%) was significantly less and percentage of energy from carbohydrate was significantly higher (55.4%) than students who reside with their parents. Elevated intake of phosphorus and retinol accompanied by inadequate intake of riboflavin, calcium, iron and copper was exhibited in both residence-type related sub-groups of investigated female pharmacy students.

[Obesity development associated with viral infections]. / Infekcje wirusowe w etiologii rozwoju otylosci.

This overview of the significance of viral infections in the development of human obesity is presented within context of the commonly recognized obesity risk factors, including the personal and public health consequences of obesity in various countries. In addition, the results of past and recently published studies on the recognition of six taxonomically different viruses which can undoubtedly be associated with obesity progression in some species of animals are summarized. More attention is focused on the results of preliminary epidemiological studies indicating that human infection by the avian adenovirus SMAM-1 or the human adenovirus Ad-36 can be objectively related to symptoms, prevalence, and complications of obesity in some adult men. Proposed pathogenic pathways involved in the observed cases of viral infection-dependent obesity in animals and humans are also briefly described. Urgent implementation of high-throughput diagnostics procedures is advised to extend viral infection-oriented modes of prevention, recognition, and therapy of obesity currently available in modern societies.

New potential phytotherapeutics obtained from white mulberry (Morus alba L.) leaves.

The present work demonstrates the profound and unique phyto-pharmacological and nutritional profile of white mulberry (Morus alba L.) leaves which containing considerable amounts of easy digestive proteins, carbohydrates, micro- and macronutrients, polyphenols, free amino acids, organic acids. The wide range of significant biopharmaceutical activities of the aqueous and polar organic solvents extracts from mulberry leaves - including antidiabetic, antibacterial, anticancer, cardiovascular, hypolipidemic, antioxidant, antiatherogenic, and anti-inflammatory - have been critically discussed. The main objective was to demonstrate the results of recently published study on the components of white mulberry leaves exhibiting their biological activity in the various pathological and health human ailments. In addition, we intend to drawn the attention of researchers and public health workers for the extended exploration of this deciduous plant leaves as the source of potential indigenous nutraceuticals and functional food products to enable development of alternative prevention and treatment protocols offered in therapy of the common non-communicable diseases and malignances.

[Potentiometric detection of beta-adrenolytic and beta-adrenergic drugs in HPLC systems]. / Potencjometryczna detekcja leków beta-adrenolitycznych oraz beta-adrenergicznych w ukladach HPLC.

This paper presents a comprehensive review of reference literature and the principal results of our own studies on the use of inclusion effects of macrocyclic compounds in the potentiometric detection of hypotensive and antiarrhythmic drugs as well as bronchodilators following their separation in HPLC systems. It was found that the properties of the liquid membrane electrodes embodying some macrocyclic compounds (i.e. trioctylated alpha-cyclodextrin, dibenzo-18-crown-6 or calix[6]arene hexaethylester) enabled reasonable prediction of their sensitivity in terms of the computed hydrophobicity and polarizability parameters of the analyzed drugs. The statistically significant equations enabling the optimalization of the composition of liquid membrane electrodes and the prediction of their detection limits in relation to the molecular structures of cationic drugs were established by applying multiparameter regression procedures. In particular it was indicated that the use of a liquid membrane electrode with trioctylated alpha-cyclodextrin enables sensitive detection (<10(-8) M) of highly hydrophobic drugs (logP >2.5 on the Parham-Hall-Kier scale) such as clenbuterol, bufuralol, and propanolol under HPLC conditions. These results indicate that the developed potentiometric detection method of hypotensive drugs can be considered as a promising alternative to the immunoassay procedures (ELISA) currently recommended for the toxicological determination of trace amounts of the drugs in biological samples. It was also shown that the set of experimentally determined detection limits characterizing the sensitivity of the four different liquid membrane electrodes used in the cation-exchange HPLC system enabled reliable screening and proper pharmacological classification of the beta-adrenergic and beta-adrenolytic drugs analyzed. Using principal component analysis (PCA) of the potentiometric data, it was stated that a differentiation of cardioselective from non-cardioselective beta1-blockers commonly administered as the hypotensive drugs was possible. This result indicates that the new method of potentiometric detection in HPLC systems can be applied as an effective high-throughput screening (HTS) procedure of large combinatorial libraries of newly synthesized drug-like candidates. This may increase the possibilities of identifying the lead compounds to be directed to further specialized biological tests, thus enabling the successful design and formulation of a new generation of more selective and pharmacogenome-oriented hypotensive drugs with reduced side-effects.

Integrated acquisition of analytical and biopharmaceutical screening data for beta-adrenergic-drugs employing diversified macrocycle supported potentiometric detection in HPLC systems.

Potentiometric detection with poly(vinyl chloride) (PVC) based liquid membrane electrode coatings is presented for a series of eighteen beta-adrenoceptor binding drugs (five agonists and thirteen antagonists) in cation exchange-HPLC and RP-HPLC systems. Incorporation of lipophilic cation-exchanger tetrakis(p-chlorophenyl)borate (TCPB) alone or in combination with trioctylated alpha-cyclodextrin into the polymeric liquid membrane gives very sensitive responses for racemic forms of bufuralol, propranolol, carazolol, clenbuterol, mabuterol, cimaterol, bisoprolol, oxprenolol, alprenolol, tertatolol, and bevantolol, especially in the cation-exchange HPLC system applying acetonitrile -- 40 mM phosphoric acid (15: 85, v/v, pH* = 2.35) as the mobile phase. In both applied orthogonal HPLC modes we observed that use of TCPB containing electrodes (no addition of neutral macrocyclic ionophores) gives more than five fold improvement in limit of detection down to 10(-7) M for mabuterol, bufuralol, alprenolol and tertatolol in comparison with UV detection. These results suggest that potentiometric detection, especially in RP-HPLC employing hybrid polymer-silica packings, can be considered as the promising alternative in the high-throughput drug abuse or doping control procedures of investigated beta-adrenergic agonists and beta-adrenolytics in humans and animals. The quantitative structure - potentiometric response relationships were developed for a set of eighteen beta-adrenenergic drugs and a set of PVC based electrodes using TCPB alone or in admixture with trioctylated alpha-cyclodextrin, dibenzo-18-crown-6 or calix[6]arene hexaethylacetate ester. A multiple linear regression model based on computationally derived set of molecular descriptors was used to predict detection limits of beta-blocking agents and beta-adrenergic agonists from their molecular structure in the developed potentiometric detectors. Principal components analysis (PCA) of data considering determined potentiometric detection limits revealed that it can be used to establish a reliable pharmacological classification of compounds with beta-adrenoceptor activity, especially for the differentiation of cardioselective and non-cardioselective beta1-antagonists.

Effect of stationary phase structure on retention and selectivity tuning in the high-throughput separation of tocopherol isomers by HPLC.

Four stationary phases containing different groups such as: C18, C30, alkylamide, and cholesterolic, were presented for simultaneous HPLC analysis of structural isomers of tocopherol. Especially, the influence of stationary phase structure and properties on tuning of the highly selective HPLC separation of beta- and gamma-tocopherol pair demonstrating, respectively, para- and ortho- arrangement of methyl substituents on the 6-chromanol ring, has been elucidated. It was pointed out that selectivity of each stationary phase has been a result of modulation in the mass transfer and set of unspecific interactions in the tertiary system comprising analyte <==> stationary phase <==> mobile phase. Differences in observed retention and specific selectivity of tocopherols together with the stationary phase structure investigations indicated that a spatial organization changing of chemically bonded ligands as predominantly a solvation consequence. Additional molecular modeling studies preliminary explained some of these complicated supramolecular phenomena which caused that cholesterolic stationary phase offered beneficial performance in screening of tocopherols by HPLC and biomimetic studies of not completely recognized interactions of tocopherol isomers and biological membranes.

Potentiometric quasi-array employing calixarene derivatives for the high-throughput similarity/diversity screening of beta-adrenergic and beta-blocking chiral drugs by HPLC.

Performance of potentiometric quasi-array detection system consisted with the seven poly (vinyl chloride) (PVC) based liquid membrane electrodes in the cation-exchange HPLC using acetonitrile--40 mM phosphoric acid (15 : 85, v/v, pH* 2.35) for assessing of molecular similarity/diversity in a mini-library of beta-adrenergic and beta-blocking chiral drugs was presented. Macrocyclic compounds differing in stability of their conformers as well as in a size, steric hindrance and polarity of its internal cavities, comprising a series of five calix[6]arene derivatives completed with one modified calix[4]resorcinarene, were used as neutral ionophores to compose mentioned set of PVC-based electrodes. The output potentiometric responses were registered in the linear supernerstian range of calibration graph of each electrode, i.e. for a constant injected concentration 2.0 x 10(-4) M of investigated drugs, which is related to the amount frequently used at in vitro studies on pharmacological effects of these drugs. The impact of symmetry oriented supramolecular interactions on the responses of developed electrodes were characterised with proposed series of the highly significant quantitative structure-potentiometric response relationships (QSPRRs) combining both three-dimensional (3D) molecular descriptors of analysed drugs as well as lipophilicity and volume polarizability of calixarene-type ionophores. The principal components analysis (PCA) and unweighted hierarchical clustering analysis (HCA) were used as the pattern recognition techniques into collected potentiometric database for extraction of the useful information on the molecular and pharmacological similarity/diversity of analysed drugs, thus a high-throughput and consistent identification of therapeutically relevant agonists of beta2- and beta3-adrenoceptors and antagonists of beta1-adrenoceptor was especially achieved. This evidence supports also a hypothesis formulated by results of homology modelling on the subtle significance of an unrecognised supramolecular insertion processes of the chiral drug molecule into the flexible hydrophobic pocket(s) formed by seven helical transmembrane moving domains of beta-adrenoceptors on their final activation, sequestration, down-regulation or blockade.

Potentiometric detection of exogenic beta-adrenergic substances in liquid chromatography.

Potentiometric detection with poly(vinyl chloride) (PVC) based liquid membrane electrode coatings is presented for a series of 18 exogenic beta-adrenergic substances in cation-exchange-HPLC and RP-HPLC systems. In both types of HPLC modes employing hybrid polymer-silica packings we observed that use of tetrakis(p-chlorophenyl)borate (TCPB) containing electrodes yielded limits of detection (DL) down to 10(-7)-10(-8) M (injected concentrations). The use of eluents with high concentrations of acetonitrile (up to 55%) yielded detection limits down to 10(-9) M (injected concentrations). A quantitative structure-potentiometric response activity relationship (QSAR) was developed for the set of beta-adrenergic substances and for a set of PVC-based electrodes using TCPB alone or in admixture with trioctylated alpha-cyclodextrin, dibenzo-18-crown-6, or calix[6]arene hexaethylester. A multiple linear regression model based on a computationally derived set of 14 molecular descriptors allowed prediction of the detection limits of beta-adrenergic substances and other amine substances from their molecular structure.

Simultaneous high-throughput determination of clenbuterol, ambroxol and bromhexine in pharmaceutical formulations by HPLC with potentiometric detection.

Potentiometric detection of clenbuterol, ambroxol and bromhexine in marketed pharmaceuticals was described in six isocratic HPLC systems. The podant- and macrocyclic-type neutral ionophores, N,N,N',N'-tetracyclohexyl-oxybis(o-phenyleneoxy)diacetamide (TOPA) and hexakis(2,3,6-tri-O-octyl)-alpha-cyclodextrin (OCD), were applied in poly(vinyl)chloride (PVC)-based liquid membrane electrodes. Both types of neutral ionophores improve the sensitivity for all mentioned drugs when compared with a tetrakis(p-chlorophenyl)borate (BOR)-based electrode as well as with single wavelength UV detection. Detection limits (S/N=3) of 2.6 x 10(-10) mol l(-1) (injected concentration) for the highly hydrophobic bromhexine were achieved with the TOPA-based electrode and a cyano reversed-phase (RP)-HPLC with Uptisphere UP5CN-25QS silica column (250 x 4.6 mm i.d.) eluted with acetonitrile (AcN)-ethanol-perchloric acid (1.66 mM) (60:2:38, v/v/v) (pH* 2.45). Comparable result was obtained with OCD-based electrodes and an XTerra RP18 hybrid silica-polymer column eluted with AcN-phosphoric acid (20 mM) (25:75, v/v) (pH* 2.60). In the mobile phases containing 60-75% v/v AcN or methanol, stable and reproducible response of both types of neutral ionophore-based electrodes was observed for at least 3 days. The results of the validated procedure for reliable simultaneous determination of the drugs in fortified representative samples of pharmaceuticals were also presented.

A novel potentiometric approach for detection of beta-adrenergics and beta-adrenolytics in high-performance liquid chromatography.

Potentiometric approach enabling sensitive and reliable detection for a series of 20 autonomic beta-adrenergic ligands with the use of poly(vinyl chloride) (PVC) based liquid membrane electrode coatings in the normal-bore cation exchange HPLC and narrow-bore reversed phase HPLC system is presented. It was found that in both kinds of HPLC modes with a contemporary hybrid polymer-silica packings an application of electrodes containing a tetrakis(p-chlorophenyl)borate (TCPB) gives limits of detection below to 8.0x10(-7) mol l(-1) (injected concentrations). In case of highly hydrophobic beta-adrenergic drugs the use of binary aqueous mobile phases with high concentrations of acetonitrile (up to 25% v/v) shifting an observable detection limits (DL) down to 2.0x10(-8) mol l(-1), especially for electrodes with addition of trioctylated alpha-cyclodextrin. The characteristics of developed potentiometric detectors was established by proposed a quantitative structure-potentiometric response relationships (QSPRRs) for a series of diversified beta-adrenergic compounds and for a set of the PVC based electrodes using TCPB alone as well as in combination with trioctylated alpha-cyclodextrin, dibenzo-18-crown-6, or calix[6]arene hexaethylester as the neutral macrocycle ionophore. A highly significant QSPRRs equations were obtained leading to reasonable prediction of the DL of specified electrodes in terms of the computationally derived set of molecular descriptors of beta-adrenergics and beta-blocking agents and similar amino alcohol type xenobiotics.