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Biomedical subjects

G Schill

Publications and source records attributed to G Schill.

At least 19 recordsLinked to original sources

Retention processes on alpha 1-acid glycoprotein-bonded stationary phase.

Stereoselective separations of charged enantiomers on CHIRAL-AGP can be controlled by varying the pH and adding charged and uncharged additives to the mobile phase. The interaction with the selector, alpha 1-acid glycoprotein, was studied by monitoring the effects of the variables on retention and by indirect detection, in part using a simple multivariate design. The stereoselectivity is due to simultaneous retention processes involving ion-exchange and ion-pairing mechanisms. The predominant mode of interaction for different solutes was elucidated from variables that promote or counteract either of the processes. Considerable improvements in the stereoselectivity were achieved with chiral or achiral anionic and cationic additives that act in a synergistic or competitive mode.

Buffers↗

Liquid chromatographic separation of the enantiomers of metoprolol and its alpha-hydroxy metabolite on Chiralcel OD for determination in plasma and urine.

The two enantiomers of metoprolol and the four enantiomeric forms of alpha-hydroxymetoprolol were separated by liquid chromatography on a Chiralcel OD column containing a cellulose tris(3,5-dimethyl-phenylcarbamate) chiral stationary phase. The column efficiency was strongly dependent on the flow-rate and the enantioselectivity was influenced by temperature. Of utmost importance for the chiral separation was the water content of the mobile organic phase. The separation system was used for the separation and determination of the enantiomers in plasma and urine samples. The metoprolol enantiomers could be determined by fluorescence down to 10 nmol/l of each in plasma with a relative standard deviation of less than 15%.

Animals↗

Enantioselective determination of metoprolol in plasma by liquid chromatography on a silica-bonded alpha 1-acid glycoprotein column.

The enantiomers of metoprolol were determined in plasma samples after direct resolution on a silica bonded alpha 1-acid glycoprotein column. Metoprolol was extracted from plasma into a diethyl ether-dichloromethane mixture and after back extraction to dilute phosphoric acid and adjustment of pH the sample was injected on a Chiral-AGP column for separation of R- and S-metoprolol. It was possible to measure down to 2 nmol per litre plasma with a relative standard deviation of less than 15% by use of gradient elution and fluorescence detection. The analytical method was employed to study the pharmacokinetics of the metoprolol enantiomers after administration of the racemate to humans.

Chromatography, Liquid↗

Application of indirect detection methods in biomedical analysis.

Indirect detection is a technically simple method to follow and quantify compounds without inherent detector response in high-performance liquid chromatography. A detectable component is added to the mobile phase and peaks are obtained for injected solutes as well as for mobile phase additives (system peaks). The underlying principle can be expressed by simple equations which show how the detection sensitivity can be optimized. The detection technique can be applied to uncharged as well as charged compounds, but the sensitivity is considerably higher for ionic solutes. The response is unspecific and the technique should preferably be applied to samples with a limited number of components. Determinations in pharmaceutical products and quantification of impurities in substances are typical fields of application. Different detection principles can be used but UV absorbance is so far the dominant technique. The chromatographic system must be stable, and efficient thermostatting is essential. Indirect response effects can give rise to disturbances when the presence of a detectable component in the mobile phase is unknown or overlooked. The understanding of the underlying principle for the indirect detection is essential for tracing or preventing such disturbances.

Chemistry, Clinical↗

Chiral separations of cationic and anionic drugs on an alpha 1-acid glycoprotein-bonded stationary phase (EnantioPac). II. Influence of mobile phase additives and pH on chiral resolution and retention.

The influence of mobile phase additives and pH on chiral resolution and retention on a high performance liquid chromatographic chiral stationary phase composed of alpha 1-acid glycoprotein bonded to diethylaminoethyl silica (EnantioPac) has been investigated. Cationic and anionic compounds of widely differing structures were chromatographed and drastic effects on stereoselectivity were observed with hydrophobic charged modifiers. For cationic solutes, a decrease in the pH of the mobile phase from 7.0 to 6.0 gave reduced retention and, in some cases, improved selectivity when tetrabutylammonium or tetrapropylammonium bromide was used as modifier. For anionic solutes, a pH decrease from 6.6 to 6.1 gave enhanced retention but without a significant change in stereoselectivity. The steric bulk and hydrophobic moieties of the solute seem to have a strong influence on chiral selectivity. Widely different separating efficiencies were obtained with molecules of different structures.

Alcohols↗

Separation of enantiomeric amines by ion-pair chromatography.

A high-performance liquid chromatographic method for the separation of optical isomers (enantiomers) of amines is described. It is based on ion-pair chromatography with a chiral counter ion in a system with an organic mobile phase and an adsorbing stationary phase. The method has been applied to enantiomers of 1-aryloxy-3-isopropylamine-2-propanol derivatives (alprenolol, metoprolol, propranolol) which are completely resolved with (+)-10-camphorsulphonate as the counter ion. Studies of the influence of the counter-ion structure and the mobile phase composition are presented.

Alprenolol↗

Ion-pair chromatography of acidic drug metabolites and endogenic compounds.

Liquid-liquid chromatographic systems based on ion-pair partition with silica microparticles as the support for the stationary phase have been used for the separation of anionic compounds of biochemical and pharmacological interest. A high separating efficiency can be obtained with both aqueous and organic mobile phases and the retention is easily regulated by the nature and the concentration of the quaternary ammonium counter ion, present in the aqueous phase. The influence of the composition of the liquid phases on the selectivity and separating efficiency has been studied, as well as equilibration methods and the stability of the systems. Examples are given of separations of sulphonamides, barbiturates, glucuronic and sulphuric acid conjugates of steroidal compounds and phenols glycine conjugates of carboxylic acids (hippuric, nicotinuric and salicyluric acid) and anionic metabolites of biogenic amines (indoleacetic, benzoic, mandelic and phenylacetic acid derivatives).

Barbiturates↗

[Studies on biotechnical ovulation synchronization in young cows. 1. Ovulation periods, ovarian findings and fertilization results after use of Metallibur, 750 IE PMS and 250 or 500 IE HCG].

The following treatment was applied to 50 mature young sows in two experiments (22 and 28 animals) throughout 20 days: Turisynchron-Prämix (Turi.), 5 g/animal, and 750 IU PMS (Prolosan serum) 28 hours after Turi. In the first experiment. 250 IU HCG (Gonabion) were additionally injected to each of twelve animals 100 hours after Turi., while in the second experiment each of ten animals recieved 500 IU HCG 103 hours after Turi. The remaining animals of the two groups were used as controls. Inseminations took place 101 and 104 hours (fourth day) after Turi. in the first experiment and 125, 149, as well as 173 hours (fifth, sixth, and seventh days) after Turi. in the second. Onset of ovulation was brought forward to the sixth day after Turi. in response to 500 IU HCG by laparotomy performed in the mornings and evenings of the fourth through seventh days. Most of the controls and test animals with 250 IU HCG ovulated on the sixth or seventh day after Turi. Ovulation was stimulated by both HCG dosages, in comparison to the controls, which was established by slaughtering the animals between the seventh and twelfth days after Turi. The percentage of ovulations was higher among the test animals and that of ovarian cysts lower. Fertilisation of the second group was clearly better than that in the first where insemination had taken place two days prior to ovulation, that is too early. The latter results were secured by tubal douche and ovocyte tests.

Animals↗