Pharmacokinetics and protein binding of three sulfonamides in sheep.
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Biomedical subjects
Publications and source records attributed to M Debackere.
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A method has been developed for quantification of bromhexine in plasma using gas chromatography mass spectrometry with selected ion monitoring. A deuterium labelled analogue was synthesized and used as the internal standard. To evaluate the gas chromatographic electron capture detection method described earlier, 23 plasma samples have been analysed by both techniques. Although a good correlation was shown, selected ion monitoring was superior to the electron capture detection method for levels below 3 ng ml-1. The mass spectrometric method has also been used to set up a pharmacokinetic study of bromhexine in horses. Urine extracts were subjected to gas chromatographic mass spectrometric analysis to identify the different metabolites of bromhexine. Three groups of metabolites were detected and identified.
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Recoveries of a series of sympathomimetic central nervous stimulants in human urine are measured using either adsorption chromatography on self-filled columns (method A) or with a special resin method suitable for racehorse urine (method B). The Amberlite resins used are XAD-2, XAD-4, XAD-7 and XAD-8 and elution is performed using chloroform. The reported comparative drug extractabilities indicate that in most instances the recoveries follow the sequence XAD-4 greater than XAD-2 approximately XAD-8 greater than XAD-7 using method A. Based on the recovery and purity of the extracts obtained, XAD-8 is preferred for gas chromatographic analysis while XAD-4 is very suitable for thin-layer chromatographic screening work. Comparing the two methods, equally good or better results were obtained with method A for all of the resins studied except XAD-7. Finally, it was found that the effect of refrigerated storage of the resins on the drug extractabilities for central nervous stimulants could be neglected.
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It is well known that nikethamide (N,N-diethylnicotinamide, CoramineR) is metabolized very rapidly to nicotinamide. Hence, there is difficulty in proving that nikethamide has been used as a doping substance because nicotinamide is a normal physiological metabolite in the organism as well as a vitamin preparation. However, an intermediate metabolite (N-ethylnicotinamide) was found by us in the urine of horses treated with CoramineR. This was characterized by gas chromatography/mass spectrometry, and synthesized and identified as being N-ethylnicotinamide. The excretion and metabolism of nikethamide after intramuscular injection in the horse was followed using quantitative gas chromatography of urine extracts over a period of several hours and the results of these experiments are reported. Changes in urinary pH had no significant effect upon either the metabolism or rate of excretion of the drug.
Experiments were carried out to test the effect of implantation of Implix¿ (20 mg estradiol + 200 mg testosterone) or Revalor¿ (140 mg trienbolone acetate + 20 mg estradiol) on growth, feed conversion, slaughter quality, and residue levels in black Friesian bull calves at 4, 8, or 4 and 8 weeks before slaughtering. Weighings and calculations of feed conversion were carried out weekly. The control group of weight gain and feed conversion consisted of 22 calves; the chemical analyses of the control group was restricted to 8 animals. Implantation of the hormones at 4 or 8 weeks before slaughtering resulted in a significant beneficial effect on weight gain, feed conversion and carcass index over the control. This effect was improved (up to 15%) by implanting the hormones at 8 and 4 weeks before slaughter. The effects obtained with Revalor seemed to be superior to those obtained with Implix. In 75% of the treated animals, some remainder of implants was found. No effect was found on water binding capacity and colour of raw meat. Carcass quality was not significantly improved as judged from water, fat, ash, and protein content of the M. Longissimus Dorsi. The collagen content of the animals treated with Revalor was slightly, though not significantly, increased. There is a slight decrease in the relative bone content of the treated animals over the control resulting in higher meat percentages. Residues were determined in meat obtained from rib and neck by biological and chemical methods. Oestrogenic activity was found in only 7 samples from the neck; all samples from the rib were negative. Chemical examination indicates the presence of oestradiol in these samples. No residues of trienbolone could be detected in the meat samples. The Pars Dissiminata of the prostate was examined histologically on frozen and paraffin sections. Although the latter permitted a sharper interpretation, both methods indicated an increased activity of the prostates induced by hormone treatment. Compared to Implix, Revalor treatment provoked a more pronounced mucous activity. In recent years, the administration of estrogens in combination with testosterone or with trenbolone acetate (androst-4,9[10]-11-trien-3-one 17-acetate)2,3,4,17 has been shown to improve the growth rate and feed conversion5,14,17 in farm animals. However, there is a lack of information on carcass quality, which is of interest to the producer as well as to the consumer. Moreover, there are sample data14 about the residue levels remaining in the carcass following hormone implantation. These experiments were carried out to test the effect of the implantation of Implix¿ (20 mg estradiol + 200 mg testosterone) or Revalor¿ (140 mg trienbolone acetate + 20 mg estradiol) on growth, feed conversion, slaughter quality, and residue levels in black Friesian bull calves.
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A gas-chromatographic (g.l.c.) method with electron-capture (e.c.) detection is described for the simultaneous quantitative determination of nanogram concentrations of 2-ethylamino-3-phenyl-norbornane (Fencamfamine, REACTIVAN) and its metabolite 2-amino-3-phenylnorbornane in urine. The renal excretion of fencamfamine and its metabolite after oral administration to humans was followed over a period of several days. The excretion of both substances was affected by urinary pH. Excretion peaks were obtained 2-4 h after ingestion and the total amount excreted during 80 h varied from 11.9 to 33.2 per cent. Based on urinary values, the biological half life of fencamfamine was 16 h. The intake of acetazolamide shortly after fencamfamine resulted in a decrease of the fencamfamine excretion and a suppression of the metabolite output during at least 10 h. Acetazolamide did not influence the percentage of the doses excreted during 80 h. No changes occurred in urinary fencamfamine or metabolite concentrations during storage of urine at -18 degrees for 6 weeks.
Crotethamide and cropropamide, both components of the respiratory stimulant prethcamide, are metabolized in humans by demethylation of the [(dimethylamino)-carbonyl]-propyl moiety. The resulting metabolites are characterized by gas chromatography-mass spectrometry of urinary extracts. The use of HCl to prevent losses by volatilization during the evaporation step, combined with methanol as solvent, complicates gas liquid chromatographic analysis of prethcamide. The resulting artifacts are identified.
A capillary gas chromatographic method with nitrogen specific detection is presented for measuring pseudoephedrine and its major metabolite norpseudoephedrine in urine after derivatization with trifluoroacetic anhydride. After the oral intake of 49.2 mg pseudoephedrine (ACTIFED) the active substance is nearly quantitatively excreted in urine over a 48 hr period. From 1 to 7 percent is metabolized to norpseudoephedrine. The intake of acetazolamide results in a suppression of the pseudoephedrine concentration for at least 12 h. The diuretic effect after the intake of 1.51 mineral water could be compared with the effect obtained with 1 mg bumetanide and results in a decrease in pseudoephedrine concentration by a factor 4 for several hours.