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Biomedical subjects

A Hulshoff

Publications and source records attributed to A Hulshoff.

At least 37 records · Page 2Linked to original sources

The determination of aminoglycoside antibiotics in serum: a comparison of a high performance liquid chromatographic method with a microbiological assay.

A high performance liquid chromatographic (HPLC) method for the determination of gentamicin and tobramycin in serum is compared with a microbiological method. The determination of gentamicin by chromatographic methods is complicated by the fact that gentamicin is a mixture of related compounds, giving rise to several chromatographic peaks. Good results were obtained when the sum of the peak heights of the chromatographic peaks corresponding with the gentamicin components are taken as a measure for the gentamicin concentration. Accuracy, precision and selectivity of the methods are discussed.

Anti-Bacterial Agents↗

Hexamethylmelamine and hexamethylmelamine hydrochloride.

Methods of analysis of the anticancer drug hexamethylmelamine, its physicochemical properties, its therapeutic uses and its fate in vivo upon oral administration, are described. The data are taken in part from the literature, in part from our own studies. The low solubility of hexamethylmelamine in water has prevented the parenteral administration of the drug to humans. The preparation of the water-soluble monohydrochloride of hexamethylmelamine, which may be suitable for this purpose, is reported, as well as its physicochemical characteristics and methods of analysis.

Altretamine↗

Analysis of creams. III. Application of gas--liquid chromatography. Part I.

The possibilities of the gas--liquid chromatographic analysis with flame ionization detection of creams of the o/w emulsion type were investigated. Interferences by cream base components in the determination of the active compounds were studied. It appeared to be possible to determine active compounds with a retention index lower than 1900 on ov-17 (e.g. methyl salicylate, menthol, thymol camphor) without clean-up of the cream samples; for the determination of compounds with retention indices between 1900 and 3700, a simple clean-up step suffices. The possible analysis of some of the cream base components together with the active compounds of the creams was investigated as well. Cetomacrogol emulsifying wax, lanette was sx and cetiol v could be determined easily, whether or not a sample clean-up step was incorporated.

Cetomacrogol↗

Analysis of creams. II. Quantitative determination of drugs in creams by titration in non-aqueous solvents.

The possibilities for the determination of active components in creams by acid-base titrations in non-aqueous solvents were investigated. Interference by cream-base components with the titration of weak organic bases and their halides with perchloric acid in acetic acid, and with the titration of weak acids with tetrabutylammonium hydroxide in N,N-dimethylformamide were studied. It appeared to be possible to determine alkaloid halides, salicylic acid, hexachlorophene and methyl salicylate without previous clean-up of the cream samples.

Ointments↗

Alkylation with alkylhalides as a derivatization method for the gas chromatographic determination of acidic pharmaceuticals.

The various types of alkylation reactions with alkyl halides and their application in the gas chromatographic analysis of acidic compounds of pharmaceutical interest are reviewed. An extensive survey of the use of these methods for the analysis of various (classes of) compounds is given, with special reference to their determination in biological matrices.

Alkylation↗

Micro-determination of tobramycin in serum by high-performance liquid chromatography with ultraviolet detection.

A procedure for the high-performance liquid chromatographic determination of tobramycin in serum is described using pre-column derivatisation with 1-fluoro-2,4-dinitrobenzene and subsequent chromatographic analysis on a reversed-phase column with ultraviolet detection. Gentamicin is used as the internal standard. The sensitivity is 0.5 mg/l with 50-microliters samples. Precision, expressed as the coefficient of variation, is 3% or better in the concentration range 0.5-16 mg/l. The absolute recovery of tobramycin is 41%. The analyses of serum samples obtained in an in vivo experiment correlated well with the results from a microbiological assay. The influence of variation of derivatisation conditions and the implications for the reliability of the internal standardisation were studied. The 2,4-dinitrophenyl tobramycin derivative was synthesized and its structure was proved to be the fully derivatized tobramycin. Side-products of the derivatisation reaction were isolated.

Anti-Bacterial Agents↗

High-performance liquid chromatographic analysis of nitroxoline in plasma and urine.

A high-performance liquid chromatographic method has been developed for the determination of nitroxoline in 50-microliter plasma and urine samples. A structural analogue of nitroxoline, 8-hydroxyquinoline, was added to the eluent in order to suppress peak asymmetry. Several parameters of the eluent were studied for the optimisation of the chromatographic system. Plasma concentration-time curves were constructed for three volunteers after they had received an oral dose of 100 mg of nitroxoline. Plasma half-life was about 1 h. Within 12 h, about 1% of the dose was excreted in the urine as free nitroxoline and about 30% as conjugated metabolite of the parent compound.

Anti-Infective Agents, Urinary↗

High-performance liquid chromatographic analysis of nalidixic acid and hydroxynalidixic acid in plasma with a dynamic anion-exchange system.

A rapid high-performance liquid chromatographic method has been developed for monitoring plasma level of patients treated intravenously with nalidixic acid. The major metabolite (in vitro also active) can be determined as well; 50 microliter plasma samples are sufficient. Use is made of a dynamic anion-exchange system. Different parameters such as adsorption of the surfactant cetrimide onto the column; pH and ionic strength of the eluent, and the critical micelle concentration of the surfactant in the eluent have been studied.

Cetrimonium Compounds↗

Micro determination of gentamicin in serum by high-performance liquid chromatography with ultraviolet detection.

A procedure for the high-performance liquid chromatographic determination of gentamicin in serum is described using pre-column derivatisation and UV detection. The serum proteins are precipitated with acetonitrile and the gentamicin components in the supernatant are derivatized with 1-fluoro-2,4-dinitrobenzene. The reaction products are chromatographed on a microparticulate C18 reversed-phase column and detected at 365 nm. Sample volumes of 50 microliters are sufficient for the determination of gentamicin concentrations in, and well below, the therapeutic range.

Chromatography, High Pressure Liquid↗

Determination of hexamethylmelamine and metabolites in plasma or serum by gas-liquid chromatography with a nitrogen-sensitive detector.

A gas chromatographic method for the quantitative determination of hexamethylmelamine (HMM) and five of its metabolites in plasma (or serum) is described. After adjustment of the pH of the plasma sample to about 9.5, the compounds are extracted with chloroform containing 5% of isopropanol. Amyl alcohol is added to the extract, which is then evaporated until a small volume remains. An aliquot of this solution is injected into a gas chromatograph equipped with a nitrogen--phosphorus flame ionisation detector. Separation of the methylmelamines is achieved with a 10% Carbowax 20M--2% KOH column. By programming the oven temperature unnecessarily long retention times are avoided. Using 1 ml of plasma, concentrations as low as 5 ng/ml of HMM and its metabolites can be quantitated. The method has been applied to the determination of HMM and metabolites in plasma of patients who received oral doses of HMM.

Altretamine↗

Rapid and simple clean-up and derivatization procedure for the gas chromatographic determination of acidic drugs in plasma.

A rapid and simple clean-up and derivatization procedure that can be generally applied to the gas chromatographic (GC) determination of acidic drugs of various chemical and therapeutic classes is described. The drugs are extracted from acidified plasma with chloroform containing 5% of isopropanol, which is then evaporated. The residue is dissolved in toluene, then the drugs are back-extracted into a small volume of a methanolic tetramethylammonium hydroxide solution. The solution obtained is added to N,N-dimethylacetamide and the drugs are treated with n-butyl iodide and chromatographed as their n-butyl esters. Retention times are given for three different columns; the results show that in all but three instances one derivative is formed. The recoveries in the extraction steps were determined by GC and UV spectrophotometry. The recovery of the back-extraction and of the extraction from plasma with chloroform-isopropanol is fairly good. For some drugs toluene can be used as the extraction solvent, which has the advantage that no evaporation of the extract is necessary, and it can be extracted directly with the tetramethylammonium hydroxide solution. Chromatograms of blank plasma treated according to the described procedure do not show interfering peaks from endogenous compounds. The advantages of the proposed method are as follows. It is a standard procedure that can be used for different types of drugs, using one standard column, with no interference from endogenous compounds. Separation is achieved between drugs that differ only in the number or position of the methyl groups and between a drug and its demethylated metabolite(s). No decomposition of the products occurs during the alkylation process and injection of the resulting neutral solution is not detrimental to the column material.

Acids↗

Determination of valproic acid (di-N-propyl acetic acid) in plasma by gas-liquid chromatography with pre-column butylation.

A gas-liquid chromatographic procedure for the determination of the anti-convulsant drug valproic acid in plasma or serum is described. Valproic acid is extracted from acidified plasma (or serum) into toluene containing octanoic acid as the internal standard. The toluene layer is back extracted with a methanolic solution of tetramethylammonium hydroxide; an aliquot of the methanolic layer is mixed after phase separation with N,N-dimethylacetamide and 1-iodobutane. After centrifugation the clear supernatant (which is stable for at least 24 h) is analysed by gas-liquid chromatography, on a 3% OV17 column. The procedure is rapid and sensitive, and the back-extraction step with methanolic tetramethylammonium hydroxide results in clean chromatogram obtained from blank plasma. Sample volumes of 50 microliter suffice for the determination of therapeutic levels of VPA.

Butanes↗

Bilirubin dynamics in the Gunn rat during phototherapy.

Bilirubin dynamics were studied in homozygous Gunn rats under normal room lighting conditions and under conditions simulating phototherapy. A kinetic model was developed for the formation, distribution, and elimination of bilirubin. The decrease in plasma bilirubin concentration during illumination with low intensity [300 footcandles (fc)] and high intensity (1000-1100 fc) light was studied. The plasma bilirubin concentration in the rats decreased under phototherapy until a new steady-state concentration was reached, the decline being more rapid under high intensity light conditions. Gunn rats were also injected with a tracer dose of 14C-bilirubin following a period during which the rats were illuminated with low or high intensity light. The distribution and elimination of the labeled bilirubin were followed under continuous illumination. The chosen kinetic model, when adapted to the set of data under investigation, fit all of the data concerning bilirubin kinetics in Gunn rats under continuous illumination.

Animals↗

The effect of some cigarette smoke constituents and other compounds on the metabolism of benzo(a)pyrene in rabbit lung 9000 g supernatant.

1. The inhibitory effects, of a number of compounds, on the formation of two groups of benzo(a)pyrene metabolites in rabbit lung homogenates (9000 g supernatant) have been investigated. 2. The inhibitors comprised two groups: those inhibiting primarily benzo(a)pyrene hydroxylase activity, and those inhibiting the activity of the epoxide-metabolizing enzymes as well as hydroxylase activity. Phenol, 1-naphthol, nicotine and acetone belong to the former group; naphthalene, anthracene and chlorpromazine to the latter group. 3. The most active inhibitors also caused a significant decrease in the amount of benzo(a)pyrene bound covalently to tissue macromolecules.

Acetone↗

Quantitative correlations between albumin binding constants and chromatographic Rm values of phenothiazine derivatives.

The binding constants of 15 phenothiazine derivatives to bovine serum albumin were obtained by a circular dichroic probe technique; The lipophilicity of the drugs, measured by a reversed-phase thin-layer technique using oleyl alcohol and methanol-water mixtures as the solvents, is expressed as RMw. The binding constants were of the same order of magnitude as the literature values, and the RMw values correlated well with log P octanol values from the literature. Correlations of log K with RMw were found to be more satisfactory when corrections for the state of ionization of the phenothiazines were made, the nonprotonated species accounting for the bulk of the binding. A better correlation was obtained when contributions from both species were taken into account. Similar correlations were attempted between RMw values and enzyme inhibitory activities of these phenothiazines taken from the literature.

Binding Sites↗

Chromatographic characterization of phenothiazine drugs by a reversed-phase thin-layer technique.

A reversed-phase thin-layer chromatographic technique was used for the characterization of 26 phenothiazine drugs. With two chromatographic systems having the sam stationary phase and phase volume ratio, but mobile phases of different pH, all but two of the compounds could be identified. Rf values in the different systems were standardized by applying a reference compound to the plates next to each compound under investigation; the corrected Rf values were calculated from the differences in the Rm values of the compounds and the reference compound, and the theoretical Rm value of the reference. It was shown that Rf values for different chromatographic systems with the same stationary phase could be predicted with reasonable accuracy. The pH of the mobile phase, for which a maximum difference in Rf values was obtained for pairs of compounds, could also be calculated and corresponded well with the observed values.

Adsorption↗