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V Schurig

Publications and source records attributed to V Schurig.

At least 37 records · Page 2Linked to original sources
PubMed2000

Enantioselective stopped-flow multidimensional gas chromatography. Determination of the inversion barrier of 1-chloro-2,2-dimethylaziridine.

Enantioselective stopped-flow multidimensional gas chromatography (stopped-flow MDGC) is a fast and simple technique to determine enantiomerization (inversion) barriers in the gas phase in a range of delta G#gas(T)=70-200 kJ mol(-1). After complete gas-chromatographic separation of the enantiomers in the first column, gas phase enantiomerization of the heart-cut fraction of one single enantiomer is performed in the second (reactor) column at increased temperature and afterwards this fraction is separated into the enantiomers in the third column. From the observed de novo enantiomeric peak areas a(j), the enantiomerization time t and the enantiomerization temperature T, the enantiomerization (inversion) barrier delta G#gas(T) is determined and from temperature-dependent experiments, the activation enthalpy delta H#gas and the activation entropy delta S#gas are obtained. Enantiomerization studies on chiral 1-chloro-2,2-dimethylaziridine by stopped-flow MDGC yielded activation parameters of nitrogen inversion in the gas phase, i.e., delta G#gas(353 K)=110.5+/-0.5 kJ mol(-1), delta H#gas=71.0+/-3.8 kJ mol(-1) and delta S#gas=-109+/-11 J mol(-1) K(-1). By the complementary method of dynamic gas chromatography (GC), the apparent enantiomerization (inversion) barrier of 1-chloro-2,2-dimethylaziridine in the gas-liquid biphase system was found delta G#app(353 K)=108 kJ mol(-1). The values obtained by stopped-flow MDGC in the gas phase were used to calculate the activation parameters of nitrogen inversion of 1-chloro-2,2-dimethylaziridine in the liquid phase in the presence of the chiral selector Chirasil-nickel(II), i.e.. deltaG#liq(353 K)=106.0+/-0.4 kJ mol(-1), delta H#liq=68.3+/-1.4 kJ mol(-1) and deltaS#liq=-106+/-3.0 J mol(-1) K(-1).

Aziridines↗
PubMed2000

Pronounced Steric Hindrance for Nitrogen Inversion in 1,3,4-Oxadiazolidines Asymmetric Nitrogen, Part 83. This work was supported by the Russian Foundation for Basic Research (RFBR) (grant No. 97-03-33021) and DFG-RFBR (grant No. 98-03-04119). O.T. thanks the Fonds der Chemischen Industrie for a doctorate scholarship. Part 82: D. A. Lenev, K. A. Lyssenko, R. G. Kostyanovsky, Izv. Akad. Nauk. Ser. Khim. 2000, N7

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Journal Article↗
PubMed2000

Enantioselective analysis of levetiracetam and its enantiomer R-alpha-ethyl-2-oxo-pyrrolidine acetamide using gas chromatography and ion trap mass spectrometric detection.

A gas chromatographic-mass spectrometric method was developed for the enantioselective analysis of levetiracetam and its enantiomer (R)-alpha-ethyl-2-oxo-pyrrolidine acetamide in dog plasma and urine. A solid-phase extraction procedure was followed by gas chromatographic separation of the enantiomers on a chiral cyclodextrin capillary column and detection using ion trap mass spectrometry. The fragmentation pattern of the enantiomers was further investigated using tandem mass spectrometry. For quantitative analysis three single ions were selected from the enantiomers, enabling selected ion monitoring in detection. The calibration curves were linear from 1 microM to 2 mM for plasma samples and from 0.5 mM to 38 mM for urine samples. In plasma and urine samples the inter-day precision, expressed as relative standard deviation was around 10% in all concentrations. Selected ion monitoring mass spectrometry is suitable for quantitative analysis of a wide concentration range of levetiracetam and its enantiomer in biological samples. The method was successfully applied to a pharmacokinetic study of levetiracetam and (R)-alpha-ethyl-2-oxo-pyrrolidine acetamide in a dog.

Animals↗
PubMed2000

Enantiomer separation by complexation SFC on immobilized Chirasil-nickel and Chirasil-zinc.

The use of complexation SFC for enantiomer separation of Lewis base selectands on chiral nickel(II)- and zinc(II)-bis[(3-heptafluorobutanoyl)-10-methylene-(1R)-camphora te] chemically bonded to poly(dimethylsiloxane) (Chirasil-nickel and Chirasil-zinc) and employed as Lewis acid selectors is described. The method is especially suited for less volatile and configurationally labile racemates. The variation of the experimental parameters temperature T, pressure p and density rho of the mobile phase carbon dioxide on the retention factor k, relative retention r and chiral separation factor alpha is studied, providing insights into the mechanisms of chiral recognition under supercritical conditions. For mecoprop methyl ester (methyl 2-(4-chloro-2-methylphenoxy)propanoate) an unusual increase of alpha at increased temperature is observed on Chirasil-nickel. Supercritical carbon dioxide does not inadvertently affect the complexation equilibria between Lewis donor selectands and the Lewis acid metal selectors during complexation SFC.

2-Methyl-4-chlorophenoxyacetic Acid↗
PubMed2000

Dynamic micellar electrokinetic chromatography. Determination of the enantiomerization barriers of oxazepam, temazepam, and lorazepam.

The temperature-dependent enantiomerization barriers of oxazepam, temazepam, and lorazepam have been determined between 0 and 30 degrees C by dynamic micellar electrokinetic chromatography (DMEKC) in an aqueous 20 mM borate/phosphate buffer system at pH 8 with 60 mM sodium cholate as chiral surfactant. Interconversion profiles featuring plateau formation and peak broadening were observed and simulated by the new program ChromWin based on the theoretical plate as well as on the stochastic model using the experimental data plateau height, hplateau, peak width at half-height, wh, total retention times, tR, and electroosmotic breakthrough time, t0. Peak form analysis yielded rate constants k and kinetic activation parameters, deltaG double dagger, deltaH double dagger, and deltaS double dagger, of the enantiomerization of oxazepam, temazepam, and lorazepam. At 25 degrees C, the enantiomerization barrier, deltaG double dagger, was determined to be approximately 90 kJ mol-1 and the half-lives, tau, were determined to be approximately 21 min. The new approach allows the fast and precise determination of enantiomerization barriers in a biogenic environment and it mimics physiological conditions, as no organic modifiers or abiotic chiral stationary phases (CSP) are employed.

Algorithms↗
PubMed2000

Enantiomer separation of chiral pharmaceuticals by capillary electrochromatography.

Enantiomer separation of chiral pharmaceuticals by capillary electrochromatography (CEC) is achieved with open-tubular capillaries (o-CEC), with packed capillaries (p-CEC) or with monolithic capillaries. In o-CEC, capillaries are coated with a thin film containing cyclodextrin derivatives, cellulose, proteins, poly-terguride or molecularly imprinted polymers as chiral selectors. In p-CEC, typical chiral HPLC stationary phases such as silica-bonded cyclodextrin or cellulose derivatives, proteins, glycoproteins, macrocyclic antibiotics, quinine-derived and 'Pirkle' selectors, polyacrylamides and molecularly imprinted polymers are used as chiral selectors. Chiral monolithic stationary phases prepared by in situ polymerization into the capillary were also developed for electrochromatographic enantiomer separation.

Chromatography, Micellar Electrokinetic Capillary↗
PubMed2000

Separation and absolute configuration of the enantiomers of a degradation product of the new inhalation anesthetic sevoflurane.

In a rebreathing anesthesia circuit, the inhaled anesthetic sevoflurane degrades into at least two products, termed "compound A" and "compound B." The enantiomer separation of the chiral compound B (1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane ) by capillary gas chromatography (cGC) using heptakis (2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin as chiral selector was studied. With this cyclodextrin derivative diluted in the polysiloxane PS 86, an unprecedented high separation factor alpha of 4.1 (at 30 degrees C) was found. Consequently, the enantiomers of compound B were isolated by preparative GC and their specific rotations were measured. In addition, their absolute configurations were determined by X-ray crystallography. To collect the X-ray data, single crystals of both enantiomers were grown in situ on the diffractometer. The levorotatory enantiomer B(-) has the R-configuration while the dextrorotatory enantiomer B(+) has the S-configuration. The elution order of the compound B enantiomers on heptakis (2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin is R before S.

Anesthetics, Inhalation↗
PubMed2000

Enantiomer separation by capillary electrochromatography on a cyclodextrin-modified monolith.

A chiral monolithic stationary phase was prepared by packing a capillary with bare porous silica and sintering the silica bed at high temperature. The resulting silica monolith was polymer-coated with Chirasil-Dex, a permethylated beta-cyclodextrin covalently linked via an octamethylene spacer to dimethylpolysiloxane. Subsequently, Chirasil-Dex was thermally immobilized on the silica support and a chiral monolith of very high stability (30 kV, more than 400 bar pressure) was obtained. The enantiomer separation of various chiral compounds by monolithic (rod) capillary electrochromatography (rod-CEC) was feasible. This method was compared with capillary liquid chromatography (LC) in a single-column mode using unified equipment. About two to three times higher efficiency was found in the rod-CEC mode as compared to rod-LC. The influence of pressure-driven flow support on efficiency, resolution, elution time and baseline stability was investigated. The amount and nature of organic modifier strongly influences efficiency and resolution.

Barbiturates↗
PubMed2000

Recent progress in enantiomer separation by capillary electrochromatography.

Enantiomer separation by electrochromatography (CEC) can be performed in three modes: (i) open-tubular capillary electrochromatography (o-CEC), in which the chiral selector is physically adsorbed coated, and thermally immobilized or covalently attached to the internal capillary wall; (ii) packed capillary electrochromatography (p-CEC), in which the capillary is either filled with chiral modified silica particles or with an achiral packing material, and a chiral selector is added to the mobile phase; and (iii) monolithic (rod)-capillary electrochromatography (rod-CEC) in which the chiral stationary phase (CSP) consists of a single piece of porous solid. We present an overview on methods and new trends in the field of electrochromatographic enantiomer separation such as CEC with either nonaqueous mobile phases or stationary phases with incorporated permanent charges, or with packing beds consisting of nonporous silica particles or particles with very small internal diameters.

Carbohydrate Sequence↗
PubMed2000

Determination of the enantiomerization barrier of oxazepam by dynamic micellar electrokinetic chromatography--comparison of experiment and simulation with ChromWin 99.

The pH-dependent and temperature-controlled enantiomerization of oxazepam has been studied by dynamic micellar electrokinetic chromatography in an aqueous buffer system with sodium cholate as the chiral surfactant. Experimental interconversion profiles featuring plateau formation were simulated by the new program ChromWin 99. Peak form analysis yielded rate constants and kinetic activation parameters of the enantiomerization of oxazepam between 5 degrees C and 25 degrees C.

Chromatography, Micellar Electrokinetic Capillary↗
PubMed1999

Quantitative determination of isoflurane enantiomers in blood samples during and after surgery via headspace gas chromatography-mass spectrometry.

The quantitative analysis of the chiral volatile anesthetic isoflurane (1) for biomedical applications by means of enantioselective gas chromatography (mass sensitive detector, selected ion monitoring) was studied. Two methods for the quantification of the enantiomers in blood samples drawn during and after narcosis were compared. Either the isomeric enflurane (2) was selected as an internal standard or a single enantiomer of 1 was used for the standard addition method, an approach referred to as 'enantiomer labeling'. Concentrations up to 0.3 micromol/l of the single enantiomers could be differentiated two days after anesthesia. The presented data imply that the body clearance for (+)-(S)-1 and (-)-(R)-1 proceeds to a measurable degree of enantioselectivity.

Adult↗
PubMed1999

Headspace gas chromatography-mass spectrometry analysis of isoflurane enantiomers in blood samples after anesthesia with the racemic mixture.

Several in vivo and in vitro studies on the stereoselective potency of isoflurane enantiomers suggest beneficial effects of the (+)-(S)-enantiomer. In order to detect possible differences in the pharmacokinetics of isoflurane enantiomers, a clinical study of 41 patients undergoing general anesthesia maintained with racemic isoflurane was performed. The isoflurane enantiomers were analyzed in blood samples drawn before induction, at cessation (day 0), and up to eight days after isoflurane anesthesia (day 1-8). A multipurpose sampler (Gerstel MPS) was used for the headspace gas chromatography-mass spectrometry (GC/MS) analysis, and it was combined with a cold injection system (Gerstel CIS 3) for coldtrapping, enrichment, and focusing of the analyte. The enantiomer separation was achieved by using a capillary column coated with octakis(3-O-butanoyl-2,6-di-O-pentyl)-gamma-cyclodextrin (Lipodex E) dissolved in the polysiloxane PS 255. Detection was done in the selected ion monitoring mode with ions m/z 117 and m/z 149. An enrichment of (+)-(S)-isoflurane in all blood samples drawn after anesthesia was found. The highest enantiomer bias, up to 52-54% (+)-(S)-isoflurane as compared to 50% for the racemate, was observed on day 2 for most of the patients. Furthermore, quantification of isoflurane in blood samples of five patients was done by enantiomer labeling, employing enantiomerically pure (+)-(S)-isoflurane as internal standard. The isoflurane concentration decreased rapidly from 383 nmol/ml to 0.6 nmol/ml (mean values) eight days after anesthesia. The present study shows differences in the pharmacokinetics of isoflurane enantiomers in man. However, it is not possible to distinguish between enantioselective distribution and enantioselective metabolism, if any.

Anesthesia, Inhalation↗
PubMed1999

Recent innovations in enantiomer separation by electrochromatography utilizing modified cyclodextrins as stationary phases.

Enantiomer separation by electrochromatography employing modified cyclodextrins as stationary phases is performed in two ways. (i) Polysiloxane-linked permethylated beta-cyclodextrin (Chirasil-Dex 1) or related selectors are coated and immobilized onto the inner surface of a capillary column. Enantiomer separation is performed in the open tube and the method is referred to as open-tubular capillary electrochromatography (o-CEC). (ii) Silica-linked native beta-cyclodextrin, permethylated beta-cyclodextrin (Chira-Dex 2) or hydroxypropyl-beta-cyclodextrin are filled into a capillary column and the bed is secured by two frits. Enantiomer separation is performed in a packed column and the method is referred to as packed capillary electrochromatography (p-CEC). In a unified instrumental approach, method (i) as well as method (ii) can be operated both in the electro- and pressure-driven modes (o-CEC vs. open-tubular liquid chromatography (o-LC) and p-CEC vs. p-LC). It is demonstrated that the electro-driven variant affords higher efficiencies at comparable elution times. Employing a single open-tubular column coated with Chirasil-Dex 1, a unified enantioselective approach can be realized in which the same selectand is separated using all existing chromatographic modes for enantiomers, i.e., gas chromatography (GC), super-critical fluid chromatography (SFC), o-LC and o-CEC. As the chiral selector is utilized as a stationary phase, an additional chiral selector may be added to the mobile phase. In the resulting dual chiral recognition systems, enhancement of enantioselectivity (matched case) or compensation of enantioselectivity (mismatched case) may be observed. The overall enantioselectivity is dependent on the sense of enantioselectivity of the selectors chosen and their influence on the electrophoretic and electroosmotic migration of the enantiomers of a selectand.

Carbohydrate Sequence↗
PubMed1999

Enantiomer separation by pressure-supported electrochromatography using capillaries packed with Chirasil-Dex polymer-coated silica.

Pressure-supported electrochromatography using capillaries packed with permethyl-cyclodextrin covalently linked via an octamethylene spacer to dimethylpolysiloxane and immobilized on silica (Chirasil-Dex silica) has been employed as an efficient and rapid method for the enantiomer separation of various racemic compounds. By comparing this method with micropacked liquid chromatography (LC), employing the same column in a unified instrumental setup, micropacked capillary electrochromatography (CEC) shows higher column efficiencies and hence better resolution factors. The influence of type and concentration of buffer, amount and nature of organic modifier, and pressure support is investigated.

Buffers↗
PubMed1999

Stereoselective pharmacokinetics and pharmacodynamics of propylisopropyl acetamide, a CNS-active chiral amide analog of valproic acid.

PURPOSE: The purpose of this study was to evaluate there existed stereoselective effects in the pharmacokinetics, anticonvulsant activity, microsomal epoxide hydrolase (mEH) inhibition, and teratogenicity of the two enantiomers of propylisopropyl acetamide (PID), a CNS-active chiral amide analogue of valproic acid. METHODS: Racemic PID, as well as the individual enantiomers, were intravenously administered to six dogs in order to investigate the stereoselectivity in their pharmacokinetics. Anticonvulsant activity was evaluated in mice (ip) and rats (oral), mEH inhibition studies were performed in human liver microsomes, and teratogenicity was evaluated in an inbred susceptible mice strain. RESULTS: Following intravenous administration to dogs of the individual enantiomers, (R)-PID had significantly lower clearance and longer half-life than (S)-PID, however, the volumes of distribution were similar. In contrast, following intravenous administration of racemic PID, both enantiomers had similar pharmacokinetic parameters. In rats (oral), (R)-PID had a significantly lower ED50 in the maximal electroshock seizure test than (S)-PID; 16 and 25 mg/kg, respectively. PID enantiomers were non-teratogenic and did not demonstrate stereoselective mEH inhibition. CONCLUSIONS: (R)-PID demonstrated better anticonvulsant activity, lower clearance and a longer half-life compared to (S)-PID. When racemic PID was administered, the clearance of (S)-PID was significantly reduced, reflecting an enantiomer-enantiomer interaction.

Allylisopropylacetamide↗
PubMed1999

Chiral discrimination using an immunosensor.

Based on the stereoselectivity of immunoglobulins, we have developed a new chiral sensor for the detection of low-molecular-weight analytes. Using surface plasmon resonance detection, enantiomers of free, underivatized alpha-amino acids can be monitored in a competitive assay by their interaction with antibodies specific for the chiral center of this class of substances. The sensitivity to the minor enantiomer in nonracemic mixtures exceeds currently available methods; therefore, such immunosensors can readily detect traces of enantiomeric impurities and are attractive for a range of applications in science and industry.

Amino Acids↗
PubMed1998

Enantiomer separation by pressure-supported electrochromatography using capillaries packed with a permethyl-beta-cyclodextrin stationary.

Efficient enantiomer separation by pressure-assisted, micro-packed capillary electrochromatography (CEC) has been carried out using a permethyl-beta-cyclodextrin-modified silica support (PM-beta-CD-silica). When comparing this method with micro-packed-high-performance liquid chromatography in the single-column-mode, CEC displays higher column efficiencies (about three times higher theoretical plate numbers at comparable elution times). The pressure support (about 10 bar), applied to avoid bubble formation, has a negligible influence on elution times in CEC. The influence of the type and composition of organic modifiers is described.

Chromatography, High Pressure Liquid↗