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Biomedical subjects

J Vink

Publications and source records attributed to J Vink.

27 records · Page 2Linked to original sources
PubMed1983

Determination of the anti-ischaemic drug bepridil in human plasma using gas chromatography with nitrogen-sensitive detection.

An assay has been developed to determine the anti-ischaemic drug bepridil (as its free base) in human plasma. The assay procedure comprises n-hexane extraction from basic plasma and gas chromatography using nitrogen-selective detection. An analogue of bepridil is used as internal standard. The accuracy and precision of the assay is determined by repeated analyses of drug-free plasma samples spiked with 5, 10, 20, 100, 400 and 1000 ng of bepridil per ml of plasma. The accuracy, defined as the relative difference between the mean bepridil concentration found and the true value, was 8% or better. The precision (relative standard deviation) was 13% at the 5 ng/ml level and 5% at the 1000 ng/ml level. The assay is suitable to monitor routinely bepridil plasma levels during clinical studies.

Bepridil↗
PubMed1982

Single ion monitoring assay for the serotonin re-uptake blocker Org 6582 in plasma.

An assay method has been developed to determine the serotonin re-uptake blocker Org 6582 as its free base in plasma. As internal standard an isomer of Org 6582 is used. The assay procedure includes protein precipitation by addition of trichloroacetic acid, n-hexane extraction from basic medium and derivatization with trifluoroacetic acid anhydride. Quantification is performed using gas chromatography mass spectrometry by monitoring the molecular ions of the N-trifluoroacetyl derivatives of Org 6582 and internal standard at m/z 315. The assay method was applied to plasma samples from toxicological and from Phase I clinical studies. The assay characteristics are discussed in relation to comparable assay methods routinely employed in the authors' laboratory to monitor drug levels.

Adult↗
PubMed1982

Antiarrhythmic effects of Org 6001 in rats: correlation with plasma and tissue drug concentrations.

The antiarrhythmic effects of Org 6001 following oral administration in the rat have been assessed and correlated with plasma, myocardial and skeletal muscle drug concentrations. Arrythmias were induced by coronary artery ligation in anaesthetized rats. Org 6001 (10, 20, 50 and 100 mg/kg given 1 h before ligation) significantly reduced mortality and the incidence of ventricular fibrillation in the 0-30 min post ligation period. Only the highest dose of drug also significantly reduced the number of ventricular ectopic beats following ligation. A linear relationship was observed between the oral dose and the Org 6001 concentrations in plasma and skeletal muscle determined 90 min after drug administration. The Org 6001 concentration in the myocardium was not linearly related to the administered dose and Org 6001 appeared to be concentrated to a higher extent in cardiac than in skeletal muscle at that time. No statistically significant difference in drug levels in the ischaemic left ventricle and normal right ventricle plus septum was observed. The antiarrythmic effect of Org 6001, as measured by changes in the incidence of ventricular fibrillation, correlated with myocardial concentrations of the drug.

Androstanols↗
PubMed1980

Excretion, isolation and structure of a new phenolic constituent of female urine.

The regular occurrence of a peak due to an unidentified substance (X) in the gas chromatographic traces obtained from phenolic extracts of urine from human pregnant and non-pregnant females has been reported. The biphasic excretion of X with maxima in the luteal phase of the ovulatory cycle and relatively high levels in the first trimester of pregnancy were noteworthy and suggested that the substance may have a biological significance. Close similarities between the excretory pattern, the chemical and chromatographic properties of X and of those of the known phenolic steroids suggested initially that this compound was steroidal in nature. The same, or a similar, substance seems to be excreted in the vervet monkey (Cercopithecus aethiops pygerythrus). We now report the excretory pattern of X in more detail, the isolation of the pure compound from pooled pregnancy urine and the chemical structure. The structure determined by mass spectrometry, IR spectroscopy and NMR spectrometry is: trans-(+/-)-3,4-bis[(3-hydroxyphenyl)methyl]dihydro-2-(3H)-furanone (HPMF) and was confirmed by synthesis.

4-Butyrolactone↗
PubMed1980

Simplified method for determination of the tetracyclic antidepressant mianserin in human plasma using gas chromatography with nitrogen detection.

A simplified gas chromatographic method for determination of the antidepressant drug mianserin in human plasma is described. Application of a nitrogen-sensitive detector reduces the assay procedure to extraction, concentration and gas chromatographic determination. The method is suitable to determine mianserin in human plasma at the 1 ng/ml level on a routine basis. At the 20 ng/ml level the deviation of the mean from the true value and the relative standard deviation amount to 1.0% and 6.8%, respectively.

Chromatography, Gas↗
PubMed1980

Determination of nanogram amounts of the antiarrhythmic drug Org 6001 in biological fluids and tissues using selected ion monitoring.

An assay method has been developed to determine the free base of Org 6001 (3 alpha-amino-5 alpha-androstan-2 beta-ol-17-one . HCl) in biological samples. The assay procedure consists of protein denaturation, ethyl acetate extraction, derivatization with tert-butyldimethylchlorosilane in dimethylformamide followed by n-hexane extraction and selected ion monitoring using trideuterated Org 6001 as an internal standard. For quantitation, the signals were monitored corresponding to the masses of the [M - 57]+ ions of 2-O-tert-butyldimethylsilyl, N-formyl derivatives of Org 6001 and the internal standard at m/z 390 and m/z 393, respectively. The assay method was applied to plasma samples from the human and rat, and to rat tissues including the target organ, the heart. The relationship between the Org 6001 plasma level and clinical effect in the human, the distribution of Org 6001 in rat tissues, and the correlation between the plasma level and the amount of Org 6001 in total heart tissue of the rat were determined.

Androstanols↗