Klaus Albert

Characterization of bonded phases by solid-state NMR spectroscopy

Structure and dynamics of chemically modified silica gels have been investigated by high-resolution solid-state NMR spectroscopy. 29Si cross-polarization—magic angle spinning (CP-MAS) NMR spectroscopy yields information on variety and quantity of surface species of both pure silica gel and modified silica gel. 13C CP-MAS NMR spectroscopy reveals dynamic properties of the attached alkyl chains. The data from 29Si and 13C solid-state NMR spectroscopy can be correlated with the separation characteristics in high-performance liquid chromatography.

Characterization of chemically modified silica gels by 29Si and 13C cross-polarization and magic angle spinning nuclear magnetic resonance

Abstract Chemically modified silica gels were prepared and examined by use of solid-state 13C and 29Si cross-polarization and magic angle spinning nuclear magnetic resonance spectroscopy. By this method, one can not only distinguish between various structural elements in the surface region, but also differentiate according to their mode of preparation. The results of the original manufacturing procedures for reversed-phase high-performance liquid chromatography materials and their subsequent treatment with trimethylsilylating reagents can be investigated. It is also possible to decide whether the solvents (e.g., methanol) used in the preparation remain adsorbed at the surface or are completely removed by heat treatment. Further developments of this method of investigation may reveal the molecular mechanism of chromatographic separations.

On-Line LC-NMR And Related Techniques

Contributors. Preface. 1. LC NMR: Theory and Experiment (Klaus Albert). 1.1 Introduction. 1.2 NMR in a Flowing Liquid. 1.3 Design of Continuous Flow NMR Probes. 1.4 Experimental Arrangement for HPLC 1H NMR Coupling. 1.5 Practical Considerations, Solvent Suppression Techniques, Gradient Elution and Purity of HPLC Solvents. References. 2. LC NMR: Automation (Ulrich Braumann and Manfred Spraul). 2.1 Practical Use of LC NMR and LC NMR/MS. 2.2 Different Working Modes in LC NMR. 2.3 Use of Mass Spectrometry in the Set Up. 2.4 Measurement Procedures. 2.5 Conclusions. References. 3. Biomedical and Pharmaceutical Applications of HPLC NMR and HPLC NMR MS (John C. Lindon, Jeremy K. Nicholson and Ian D. Wilson). 3.1 Introduction. 3.2 Technical and Operational Overview. 3.3 Applications in Combinatorial Chemistry. 3.4 Application to Chemical Impurities. 3.5 Application to Chiral Separations of Pharmaceutical Mixtures. 3.6 Application to Natural Products. 3.7 Application to Chemical Reactivity of Drug Glucuronides. 3.8 Application to Futile Deacetylation Reactions. 3.9 Application to Trapping of Reactive Intermediates. 3.10 Application to Uptake and Transformation of Xenobiotics by Plants. 3.11 Separation of Lipoproteins and their Characterisation using HPLC NMR. 3.12 Superheated Water HPLC NMR and HPLC NMR MS Studies on Pharmaceuticals. 3.13 Application of Hypernation to a Mixture of Non Steroidal Anti Inflammatory Drugs. 3.14 Concluding Remarks. References. 4. Application of On Line LC NMR and Related Techniques to Drug Metabolism Studies (John P. Shockcor). 4.1 Introduction. 4.2 LC NMR Techniques. 4.3 Application of LC NMR MS to Drug Metabolism: The Structure Elucidation of Rat Urinary Metabolites of Efavirenz by LC NMR MS. Conclusions. References. 5. LC NMR for Natural Products Analysis. 5.1 Application of LC NMR and LC NMR MS Hyphenation to Natural Products Analysis (Martin Sandvoss). References. 5.2 Hyphenation of Modern Extraction Techniques to LC NMR for the Analysis of Geometrical Carotenoid Isomers in Functional Food and Biological Tissues (Tobias Glaser and Klaus Albert). References. 6. LC NMR in Environmental Analysis (Alfred Preiss and Markus Godejohann). 6.1 Introduction. 6.2 Target and Non Target Analysis. 6.3 LC NMR Coupling in Non Target Analysis. 6.4 Application of LC NMR and LC NMR in Combination with LC MS to Environmental Samples. 6.5 Simulation of Environmental Processes. 6.6 Conclusions. References. 7. Related Techniques Introduction. 7.1 GPC NMR Coupling (Heidrun Handel and Klaus Albert). References. 7.2 SFC NMR and SFE NMR (Holger Fischer and Klaus Albert). 7.3 Nanoliter NMR. 8. Future Developments Introduction. 8.1 HPLC 13C NMR (Klaus Albert). 8.2 Parallel NMR Detection (Andrew G. Webb, Jonathan V. Sweedler and Daniel Raftery). Concluding Remarks (Klaus Albert). Index.

On-line use of NMR detection in separation chemistry

Abstract The direct on-line coupling between important separation and extraction techniques such as high-performance liquid chromatography (HPLC), supercritical fluid chromatography (SFC), supercritical fluid extraction (SFE) and capillary electrophoresis (CE) and proton high-field nuclear magnetic resonance (NMR) spectroscopy is described. The resolution of the 1H NMR spectra obtained in HPLC-NMR, SFC-NMR and SFE-NMR coupling under continuous-flow conditions is similar to conventionally recorded NMR spectra. In CE-NMR coupling signal line widths are degraded but the resolution of CE-NMR spectra is improving continuously. The detection limit of a HPLC-NMR separation in acetonitrile-D2O for aliphatic signals of a low-molecular-mass compound (300 Da) is 500 ng of injected compound in the continuous-flow mode at a 600 MHz NMR spectrometer with a 120 μl flow cell. A similar detection limit in the nanogram range with a 5 nl flow cell is reached in a CE-NMR separation at a 300 MHz NMR spectrometer. In SFC-NMR coupling the whole proton spectral range can be observed without any solvent windows. SFE-NMR offers the advantage of directly monitoring the extraction process.

On-line coupling of high-performance liquid chromatography and nuclear magnetic resonance

Abstract High-performance liquid chromatography—nuclear magnetic resonance (HPLC—NMR) on-line coupling is a possible solution to the problemof universal detectors in liquid chromatogrphy. By use of a newly developed 1 H-FT-NMR* flow cell, 1 H-NMR spectra of flowing systems cn be obtained. Although sensitivity and resolution are somewhat lower than in the conventional system, the 1 H-MNMR spectra are of sufficient quality to enable classification of unknown compounds. The performed HPLC separation with on-line NMR-measurement shows the capabilities of the applied arrangement.

Separation and identification of various carotenoids by C30 reversed-phase high-performance liquid chromatography coupled to UV and atmospheric pressure chemical ionization mass spectrometric detection

In this paper the application of on-line HPLC-UV-APCI (atmospheric pressure chemical ionization) mass spectrometry (MS) coupling for the separation and determination of different carotenoids as well as cis/trans isomers of beta-carotene is reported. All HPLC separations were carried out under RP conditions on self-synthesized polymeric C30 phases. The analysis of a carotenoid mixture containing astaxanthin, canthaxanthin, zeaxanthin, echinenone and beta-carotene by HPLC-APCI-MS was achieved by scanning the mass range from m/z 200 to 700. For the characterization of a sample containing cis/trans isomers of beta-carotene as well as their oxidation products, a photodiode-array UV-visible absorbance detector was used in addition between the column and the mass spectrometer for structural elucidation of the geometrical isomers. The detection limit for beta-carotene in positive-ion APCI-MS was determined to be 1 pmol. In addition, an extract of non-polar substances in vegetable juice has been analyzed by HPLC-APCI-MS. The included carotenoids could be identified by their masses and their retention times.

On-Line Coupling of Capillary Electrochromatography, Capillary Electrophoresis, and Capillary HPLC with Nuclear Magnetic Resonance Spectroscopy

A novel capillary NMR coupling configuration, which offers the possibility of combining capillary zone electrophoresis (CZE), capillary HPLC (CHPLC), and for the first time capillary electrochromatography (CEC) with nuclear magnetic resonance (NMR), has been developed. The hyphenated technique has a great potential for the analysis of chemical, pharmaceutical, biological, and environmental samples. The versatile system allows facile changes between these three different separation methods. A special NMR capillary containing an enlarged detection cell suitable for on-line NMR detection and measurements under high voltage has been designed. The acquisition of 1D and 2D NMR spectra in stopped-flow experiments is also possible. CHPLC NMR has been performed with samples of hop bitter acids. The identification and structure elucidation of humulones and isohumulones by on-line and stopped-flow spectra has been demonstrated. The suitability of the configuration for electrophoretic methods has been investigated by the application of CZE and CEC NMR to model systems.

Chain Order and Mobility of High-Density C18 Phases by Solid-State NMR Spectroscopy and Liquid Chromatography

C(18) phases prepared by different synthetic pathways are examined by solid-state NMR spectroscopy. Silane functionality is clearly indicated by (29)Si CP/MAS NMR spectroscopy. Order and mobility of the alkyl chains are investigated with high-speed (1)H MAS and (13)C CP/MAS NMR spectroscopy. Differences in coverage are monitored by (1)H line widths,( 13)C chemical shifts, (13)C cross-polarization constants, and (1)H relaxation times in the rotating frame. It is shown that C(18) phases prepared by the surface polymerization technique exhibit a more regular surface coverage than sorbents prepared by conventional polymeric synthesis. The findings from solid-state NMR investigations are discussed in the context of liquid chromatography (LC) separations of linear and bulky polycyclic aromatic hydrocarbon (PAH) solutes.

Separation and Identification of Tocotrienol Isomers by HPLC−MS and HPLC−NMR Coupling

A crude palm-oil extract rich in vitamin E homologues was investigated by HPLC-MS and HPLC-NMR coupling. For mass spectrometry a newly introduced ionization technique called Coordination Ion Spray (CIS) was used. Through the addition of silver ions to the HPLC eluent, the ionization process of nonpolar substances is facilitated. Chromatography and all coupling experiments were conducted on a C(30) column which exhibited an extraordinary shape selectivity and overwhelming sample-loading capability. Experiments were performed with pure methanol as an eluent which proved to be ideal for NMR spectroscopy as well as mass spectrometry. All necessary information for unambiguous structural assignment was collected within 45 min of the LC-NMR experiment and 15 min of the LC-MS experiment. Six compounds were identified, i.e., α-, β-, γ-, and δ-tocotrienol, α-tocoenol, and α-tocopherol.

Liquid chromatography-nuclear magnetic resonance spectroscopy.

A general overview of the experimental set-up for performing analytical-scale and nanoliter-scale liquid chromatography-1H nuclear magnetic resonance spectroscopy (LC-1H-NMR) experiments is given. The high power of combining LC with 1H-NMR spectroscopy is demonstrated by two examples, where NMR acquisition was performed either in the continuous-flow mode on the analytical scale or in the stopped-flow mode on the nanoliter scale. Current developments employing the on-line coupling of capillary as well as supercritical fluid separation methods with 1H-NMR spectroscopy together with LC-13C-NMR spectroscopy are discussed.