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Biomedical subjects

U Holzgrabe

Publications and source records attributed to U Holzgrabe.

At least 19 recordsLinked to original sources
PubMed2006

Determination of erythromycin and related substances in commercial samples using liquid chromatography/ion trap mass spectrometry.

A sensitive, precise and accurate quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the measurement of erythromycin A (EA) and related substances in commercial samples was developed and validated. The samples were chromatographed on a reversed-phase column with a polar endcapping and analyzed by ion trap tandem mass spectrometry in the multiple reaction monitoring (MRM) mode using positive electrospray ionization. The method showed high recovery (>or=98.82%), high sensitivity (lower limit of quantitation of 0.25 ng/mL for EA and less than 7.3 ng/mL for the related substances) and high precision ( or=0.991) with a run time of only 13 min. The method was successfully applied to the determination of EA and related substances in commercial samples. Moreover, using the advanced data-dependent acquisition capability of the ion trap software two new unexpected EA related substances could be detected and possible structures for these substances were postulated.

Anti-Bacterial Agents↗
PubMed2006

Development of an enhanced separation of erythromycin and its related substances by liquid chromatography.

A new HPLC-UV method for the determination of the impurity profile of erythromycin is developed. In contrast to the liquid chromatography described in the European Pharmacopoeia the analysis could be performed at a temperature of 25 degrees C. Erythromycin samples were analysed on an endcapped RP phase with cyanopropyl groups on the surface using gradient elution with 32 mM potassium phosphate buffer pH 8.0 and acetonitrile/methanol (75:25). The aforementioned method shows clear improvements compared to the actual method of the European Pharmacopoeia, which is less selective and sensitive.

Anti-Bacterial Agents↗
PubMed2006

Characterization of bacterial growth and the influence of antibiotics by means of UV resonance Raman spectroscopy.

In this work we monitor the bacterial growth of a Bacillus pumilus batch culture by means of UV resonance Raman spectroscopy. Excitation with a wavelength of 244 nm especially enhances the Raman scattering of the aromatic amino acids and the nucleic acid bases and therefore is a good method to track the metabolic changes that occur during bacterial growth. Furthermore, a drug from the fluoroquinolone group is added to the bacterial suspension at the beginning of the exponential growth phase. With the help of chemometrical methods such as hierarchical cluster analysis (HCA) and principal component analysis (PCA) it is possible to visualize the small changes that occur in the UV resonance Raman spectra due to the interaction of the drug with its biological targets DNA and the enzyme gyrase within the bacterial cell.

Anti-Bacterial Agents↗
PubMed2005

Quantitative NMR spectroscopy--applications in drug analysis.

NMR spectroscopy being a primary ratio method of measurement is highly suitable to evaluate the quality of drugs. NMR spectroscopy can be used for the identification of a drug substance, the identification and quantification of impurities arising from the synthesis pathway and degradation, or residual solvents as well as the determination of the content in the assay. This review gives an overview of the application of quantitative NMR spectroscopy in International Pharmacopoeias and for licensing purposes.

Drug Contamination↗
PubMed2005

Vibrational spectroscopic characterization of fluoroquinolones.

Quinolones are important gyrase inhibitors. Even though they are used as active agents in many antibiotics, the detailed mechanism of action on a molecular level is so far not known. It is of greatest interest to shed light on this drug-target interaction to provide useful information in the fight against growing resistances and obtain new insights for the development of new powerful drugs. To reach this goal, on a first step it is essential to understand the structural characteristics of the drugs and the effects that are caused by the environment in detail. In this work we report on Raman spectroscopical investigations of a variety of gyrase inhibitors (nalidixic acid, oxolinic acid, cinoxacin, flumequine, norfloxacin, ciprofloxacin, lomefloxacin, ofloxacin, enoxacin, sarafloxacin and moxifloxacin) by means of micro-Raman spectroscopy excited with various excitation wavelengths, both in the off-resonance region (532, 633, 830 and 1064 nm) and in the resonance region (resonance Raman spectroscopy at 244, 257 and 275 nm). Furthermore DFT calculations were performed to assign the vibrational modes, as well as for an identification of intramolecular hydrogen bonding motifs. The effect of small changes in the drug environment was studied by adding successively small amounts of water until physiological low concentrations of the drugs in aqueous solution were obtained. At these low concentrations resonance Raman spectroscopy proved to be a useful and sensitive technique. Supplementary information was obtained from IR and UV/vis spectroscopy.

Aza Compounds↗
PubMed2004

Analysis of atropine, its degradation products and related substances of natural origin by means of reversed-phase high-performance liquid chromatography.

Chromatographic separation and quantification methods of tropa alkaloids were often described. In order to separate atropine from its degradation products ion-pair chromatography (IPC) has been frequently applied. Beside long equilibration times IPC often suffers from poor robustness. The aim of this study was to develop robust and simple HPLC methods for both stability testing of atropine solutions and limitation of related substances in atropine from plant material. Using a hydrophilic embedded RP18 column and a gradient elution gave baseline separation of all components.

Atropine↗
PubMed2003

Bisquaternary dimers of strychnine and brucine. A new class of potent enhancers of antagonist binding to muscarinic M2 receptors.

Bisquaternary dimers of strychnine and brucine were synthesized and their allosteric effect on muscarinic acetylcholine M(2) receptors was examined. The compounds retarded the dissociation of the antagonist [(3)H]N-methylscopolamine ([(3)H]NMS) from porcine cardiac cholinoceptors. This action indicated ternary complex formation. All compounds exhibited higher affinity to the allosteric site of [(3)H]NMS-occupied M(2) receptors than the monomeric strychnine and brucine, while the positive cooperativity with NMS was fully maintained. SAR studies revealed the unchanged strychnine ring as an important structural feature for high allosteric potency.

Allosteric Regulation↗
PubMed2003

Antitrypanosomal naphthylisoquinoline alkaloids and related compounds.

In view of the need to develop new drugs against human African trypanosomiasis, a series of naturally occurring naphthylisoquinoline alkaloids, axially chiral acetogenic products derived from tropical plants, have been investigated for their activity against Trypanosoma brucei brucei TC 221. Likewise compounds corresponding to the two molecular portions, the naphthalene and the isoquinoline parts were tested, as well as molecules related to the central biaryl core of the alkaloids. Among all compounds tested, the natural, genuine alkaloids themselves, in particular dioncophylline B with its biaryl system and a moderate number of free hydroxy functions, showed the highest activities. Our results demonstrate that naphthylisoquinoline alkaloids constitute an interesting novel class of antitrypanosomal compounds worth further optimization.

Alkaloids↗
PubMed2003

Structure/activity relationships of M2 muscarinic allosteric modulators.

Allosteric modulation of G protein-coupled receptors has been intensively studied at muscarinic acetylcholine receptors. Findings made with archetypal allosteric agents such as gallamine, alcuronium, and bis(ammonio)alkane-type agents revealed that binding of orthosteric ligands that attach to the acetylcholine site can be allosterically decreased or increased or left unaltered in a subtype-selective fashion. Analyses of structure/activity relationships (SARs) help to elucidate the molecular events underlying the allosteric action and they may pilot the development of new allosteric agents with improved properties and therapeutic perspectives. With a focus on SARs, this review illustrates the principles of muscarinic allosteric interactions, gives an overview of SARs in congeners of archetypal allosteric agents, and considers the topology of M(2) muscarinic allosteric interactions that are characterized by divergent binding modes.

Alcuronium↗
PubMed2002

Do we know the mechanism of chiral recognition between cyclodextrins and analytes?

The resolution of chiral phenethylamine analogue compounds were studied in presence of single-isomer neutral and negatively charged cyclodextrins (CDs) by means of capillary electrophoresis (CE) and NMR spectroscopy. Whereas the native beta-CD and heptakis(2-N,N-dimethylcarbamoyl)beta-cyclodextrin were not able to separate the racemates of four ephedrine derivatives studied, heptakis(2,3-O-diacetyl)beta-cyclodextrin and especially heptakis(2,3-O-diacetyl-6-sulfo)beta-cyclodextrin could resolve all four pairs of enantiomers in one run. UV and NMR spectroscopic measurements revealed various kinds of complexes of phenethylamines with the CDs. Either defined inclusion complexes or manifold complexes which are mostly characterized by an attachment of the analyte to the outside of the CD cavity were found. No correlation between the kind of complexation and the resolution observed by means of CE could be found.

Cyclodextrins↗
PubMed2002

Diazabicyclononanones, a potent class of kappa opioid analgesics.

The 1,5-dimethyl 3,7-diaza-3,7-dimethyl-9-oxo-2,4-di-2-pyridine-bicyclo[3.3.1]nonane-1,5-dicarboxylate, HZ2, has a high and selective affinity for the kappa opioid receptor and an antinociceptive activity comparable to morphine. In addition, it is characterized by a long duration of action and a high oral bioavailability. QSAR studies within series of kappa agonists revealed a chair-boat conformation of a double protonated HZ2 characterized by an almost parallel orientation of the C9 carbonyl group and the N7-H group and at least one aromatic ring to be the pharmacophoric arrangement. Structural variations showed that the pyridine rings in 2 and 4 position can be replaced with p-methoxy-, m-hydroxy- and m-fluoro-substituted phenyl rings. However, all other substituents have to be kept the same for a high affinity to the kappa receptor.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗