This paper presents a comprehensive review of reference literature and the principal results of o... more 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.
Potentiometric detection of N,N′-diethylaminoethanol (DEAE) and a series of physiologically relev... more Potentiometric detection of N,N′-diethylaminoethanol (DEAE) and a series of physiologically relevant lysosomotropic amino alcohols was demonstrated in cation exchange HPLC. Poly (vinyl chloride) (PVC) based liquid membrane electrode coatings were used which contained the lipophilic cation exchanger tetrakis(p-chlorophenyl)borate (TCPB) either alone or in combination with one of the macrocyclic ionophores hexakis-(2,3,6-tri-O-octyl)-α-cyclodextrin (CDX), dibenzo-18-crown-6 (CRW) or calix[6]arene hexaethylacetate ester (CLX). For all PVC membrane electrodes used, improved sensitivity over UV detection at 210nm was obtained for the analyzed aliphatic amino alcohols. Especially, addition of CLX to the PVC-based membrane leads to highly enhanced detection limits for the low molecular weight lysosomotropic amino compounds, i.e. aminoethanol and methylamine. The performance of the proposed potentiometric detection method was demonstrated in cation exchange HPLC modes employing two different aqueous mobile phase systems with pH∗ 2.30 comprising phosphoric or acetic acid with acetonitrile as organic modifier. Detection limits of 1.1×10−8 and 2.4×10−8M (injected concentrations) were achieved, respectively, for N-methylaminoethanol and hexylamine by using a CLX based electrode. Sensitive and reliable determination of DEAE, a local anaesthetic agent, after liquid–liquid or SPE extraction from fortified bovine serum samples was obtained with the HPLC method coupled with the proposed potentiometric detection system. A linear free-energy relationship (LFER) based on a general solvation equation was used to predict detection limits of amino alcohols from their molecular structure in the developed potentiometric detectors employing CLX and CRW.
Potentiometric detection with poly(vinyl chloride) (PVC) based liquid membrane electrode coatings... more 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.
Summary The changes in the chromatographic properties of MgO and MgCO3 due to thermal treatment ... more Summary The changes in the chromatographic properties of MgO and MgCO3 due to thermal treatment was investigated. The experimental results show that thermally treated MgO and MgCO3 can be used as stationary phase for the gas-adsorption chromatography of hydrocarbon mixtures.
Retention profiles in series of the neutral and highly hydrophobic 1,3,4-oxadiazoles containing c... more 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.
Cotinine, as the main metabolite of nicotine, has been determined in urine using solid-phase extr... more Cotinine, as the main metabolite of nicotine, has been determined in urine using solid-phase extraction and the high-performance thin-layer chromatographic (SPE-HPTLC) method. The urine samples were collected from a group of 35 male adolescents which were moderate or significantly exposed to home environmental tobacco smoke (ETS). l-methyl-2-pyrrolidinone was used as the internal standard in the proposed screening procedure. The thin-layer chromatograms were evaluated densitometrically after visualization of cotinine spots with ninhydrin and cadmium acetate solution. The described SPE-HPTLC procedure indicated good selectivity, sensitivity and reproducibility, enabling reliable verification of interview collected questionnaire data in families exhibiting a diversified level of ETS. The results of cotinine measurements by the proposed method were applied for assessment of hazards from home ETS on the health status of elementary schoolboys, especially an increased risk for infectious respiratory tract diseases and exercise-induced bronchospasm.
This paper presents a comprehensive review of reference literature and the principal results of o... more 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.
Potentiometric detection of N,N′-diethylaminoethanol (DEAE) and a series of physiologically relev... more Potentiometric detection of N,N′-diethylaminoethanol (DEAE) and a series of physiologically relevant lysosomotropic amino alcohols was demonstrated in cation exchange HPLC. Poly (vinyl chloride) (PVC) based liquid membrane electrode coatings were used which contained the lipophilic cation exchanger tetrakis(p-chlorophenyl)borate (TCPB) either alone or in combination with one of the macrocyclic ionophores hexakis-(2,3,6-tri-O-octyl)-α-cyclodextrin (CDX), dibenzo-18-crown-6 (CRW) or calix[6]arene hexaethylacetate ester (CLX). For all PVC membrane electrodes used, improved sensitivity over UV detection at 210nm was obtained for the analyzed aliphatic amino alcohols. Especially, addition of CLX to the PVC-based membrane leads to highly enhanced detection limits for the low molecular weight lysosomotropic amino compounds, i.e. aminoethanol and methylamine. The performance of the proposed potentiometric detection method was demonstrated in cation exchange HPLC modes employing two different aqueous mobile phase systems with pH∗ 2.30 comprising phosphoric or acetic acid with acetonitrile as organic modifier. Detection limits of 1.1×10−8 and 2.4×10−8M (injected concentrations) were achieved, respectively, for N-methylaminoethanol and hexylamine by using a CLX based electrode. Sensitive and reliable determination of DEAE, a local anaesthetic agent, after liquid–liquid or SPE extraction from fortified bovine serum samples was obtained with the HPLC method coupled with the proposed potentiometric detection system. A linear free-energy relationship (LFER) based on a general solvation equation was used to predict detection limits of amino alcohols from their molecular structure in the developed potentiometric detectors employing CLX and CRW.
Potentiometric detection with poly(vinyl chloride) (PVC) based liquid membrane electrode coatings... more 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.
Summary The changes in the chromatographic properties of MgO and MgCO3 due to thermal treatment ... more Summary The changes in the chromatographic properties of MgO and MgCO3 due to thermal treatment was investigated. The experimental results show that thermally treated MgO and MgCO3 can be used as stationary phase for the gas-adsorption chromatography of hydrocarbon mixtures.
Retention profiles in series of the neutral and highly hydrophobic 1,3,4-oxadiazoles containing c... more 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.
Cotinine, as the main metabolite of nicotine, has been determined in urine using solid-phase extr... more Cotinine, as the main metabolite of nicotine, has been determined in urine using solid-phase extraction and the high-performance thin-layer chromatographic (SPE-HPTLC) method. The urine samples were collected from a group of 35 male adolescents which were moderate or significantly exposed to home environmental tobacco smoke (ETS). l-methyl-2-pyrrolidinone was used as the internal standard in the proposed screening procedure. The thin-layer chromatograms were evaluated densitometrically after visualization of cotinine spots with ninhydrin and cadmium acetate solution. The described SPE-HPTLC procedure indicated good selectivity, sensitivity and reproducibility, enabling reliable verification of interview collected questionnaire data in families exhibiting a diversified level of ETS. The results of cotinine measurements by the proposed method were applied for assessment of hazards from home ETS on the health status of elementary schoolboys, especially an increased risk for infectious respiratory tract diseases and exercise-induced bronchospasm.
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