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Ionic liquid-modified magnetic polymeric microspheres (ILMPM) were prepared based on Fe3O4 magnetic nanoparticles (MNPs) and ionic liquids (ILs) incorporated into a polymer. The composites were characterized using scanning electron microscopy, Fourier transform infrared analysis, thermogravimetric analysis, X-ray diffraction, and vibrating magnetometer, which indicated that ILMPM had a regularly spherical shape and strong magnetic property. The obtained ILMPM were successfully applied as a special adsorbent of magnetic dispersive solid phase extraction (MDSPE) for the rapid extraction and isolation of sulfamonomethoxine sodium and sulfachloropyrazine sodium in urine. The factors that affected extraction efficiency, such as adsorption conditions, desorption conditions, washing and elution solvents, and pH of the sample solution, were optimized. Under the optimum condition, good linearity in the range of 0.005-2.0 μg g(-1) (r ≥ 0.9996) was obtained for the two sulfonamides (SAs); the average recoveries at three spiked levels ranged from 86.9 to 102.1 %, with relative standard deviations of ≤4.3 %. The presented ILMPM-MDSPE method combined the advantages of ILs, MNPs, and MDSPE and therefore could be potentially applied for rapid screening of SAs in urine.

A simple, accurate and low cost spectrophotometric method is proposed for the determination of the synthesized paracetamol derivative; 4-acetamidophenyl N'-(sulphanilamide) acetate (APSA) in biological fluids. The spectrophotometric method is based on a condensation reaction between the alcoholic solution of APSA and acidic solution of p-dimethylaminobenzaldeyde (DPMK) to generate a yellow colored product. The linear range for the determination of APSA was 1-10 µg mL(-1) with molar absorptivity of 3.6877 × 10(4) L mol(-1) cm(-1) and Sandell's sensitivity of 0.001 µg cm-2/0.001 absorbance unit. During the inter-day and intra-day analysis, the relative standard deviation for replicated determination of APSA was found to be less than 2.0% and accuracy was 99.20-101.60% and 99.10-101.30% in blood and urine samples, respectively. There was no interference with commonly used blood and urine sample. The developed spectrophotometric method was successfully applied to assess APSA in biological fluids.

Salting-out liquid-liquid extraction (LLE) uses water-miscible organic solvents as the extractants. The principle of it is based on the phase separation of water-miscible organic solvents from the aqueous solutions in the presence of high concentration of salts. As an effort to miniaturization, in the present study, a 1-mL syringe was employed as the phase separation device for salting-out LLE. Once the phase separation occurred, the upper layer could be narrowed into the needle tip by pushing the plunger; thus, the collection of the upper layer solvent was convenient. By miniaturization, the consumption of organic solvent was decreased as low as possible. Four sulfonamides were used as model analytes. The optimal salting-out parameters were as follows. 150 μL of acetonitrile was added to the 500 μL of sample solution containing 300 mg mL(-1) sodium chloride at a pH of 6.5. This procedure afforded a convenient, fast and cost-saving operation with good cleanup ability for the model analytes. It showed promising applications for different matrices. Herein, food (honey), environmental water (river water) and biological fluid (human urine) were investigated. Satisfactory results were obtained. An additional bonus of this sample preparation method is that, owing to its water-miscible nature, the extraction solvent is compatible with various analytical systems, like gas chromatography, high-performance liquid chromatography and capillary electrophoresis., (Copyright © 2010 Elsevier B.V. All rights reserved.)

In sports, thiazide diuretics are used to flush out previously taken prohibited substances with forced diuresis and in sports where weight classes are involved to achieve acute weight loss. Thiazide diuretics include compounds which are very unstable and hydrolyse in aqueous media. Because information regarding the urinary detection of the hydrolysis products is limited, urinary excretion profiles for the hydrolysis product 4-amino-6-chloro-1,3-benzenedisulphonamide were established in 6 healthy volunteers after oral administration of altizide (15 mg per tablet) and hydrochlorothiazide (25mg per tablet). Additionally, the excretion profile of chlorothiazide, a metabolite of altizide and hydrochlorothiazide, was also determined. A quantitative liquid-chromatographic tandem mass spectrometric method to detect the 4 substances was developed and validated. The result of this work shows that altizide is eliminated within 48 h in urine whereas hydrochlorothiazide was detectable after 120 h. Chlorothiazide was determined to be a minor metabolite of altizide and hydrochlorothiazide and could be detected up to 120 h. The hydrolysis product, 4-amino-6-chloro-1,3-benzenedisulphonamide, was detectable 120 h after administration, with concentrations at least 10 times higher than the parent drug. Concentrations ranged between 41-239 and 60-287 ng/mL after altizide and hydrochlorothiazide administration, respectively. The study shows that 4-amino-6-chloro-1,3-benzenedisulphonamide is an important target compound for the long time detection of thiazide diuretics in urine.

The circadian changes in the pharmacokinetics and pharmacodynamics of azosemide were investigated after intravenous and oral administration of the drug (10 mg kg(-1)) to rats at 1000 or 2200 h. After intravenous administration of azosemide the percentage of the dose excreted in 8-h urine as unchanged azosemide was significantly higher in the 1000 h group than in the 2200 h group (41.7 compared with 28.9%) and this resulted in a significant increase in 8-h urine output (84.7 compared with 36.6 mL/100 g). After intravenous administration the time-averaged renal clearance (CLR) of azosemide was significantly faster (2.86 compared with 1.76 mL min(-1) kg(-1)) and urinary excretion of sodium (46.4 compared with 25.9 mmol/100 g) and chloride (35.6 compared with 18.8 mmol/100 g) increased significantly in the 1000 h group. However, after oral administration, the percentages of oral dose of azosemide excreted in 8-h urine as unchanged azosemide were significantly higher (1.88 compared with 0.67%) and the CL(R) of azosemide was significantly faster (3.64 compared with 0.79 mL min(-1) kg(-1)) in the 2200 h group. This could be at least partly because of increased absorption of azosemide from the gastrointestinal tract in the 2200 h group; the percentages of oral dose of azosemide recovered from the gastrointestinal tract in 8 h as unchanged azosemide was significantly smaller (5.7 compared with 13.2%) in the 2200 h group. The pharmacodynamic parameters of azosemide were not significantly different after oral administration of the drug to both groups of rats. If these data could be extrapolated to man, the intravenous dose of azosemide could be modified on the basis of circadian time.

The pharmacokinetics of azosemide were evaluated simultaneously using both arterial and venous plasma data in six rabbits after a rapid 5 s intravenous bolus dosing. Initial arterial to venous ratios at 5 s after injection were the highest with values of 81.1, 67.3, 58.7, 530, 2660, and 10.5 for rabbits 1-6, respectively. Both curves decayed, paralleling each other at the terminal phase, with the venous levels higher than the arterial levels by 15.3, 31.9, 34.1, 40.7, 30.5, and 16.5% for rabbits 1-6, respectively. An exponential term with a negative coefficient was used to account for the short and steep rising phase of venous plasma levels after injection. Detailed analysis showed significant differences in various pharmacokinetic parameters, such as initial volume of distribution, apparent volume of distribution at steady state, and mean residence time based on arterial or venous data. A plot of 1/Q (urine flow rate) versus 1/CLR (renal clearance) of azosemide yielded a straight line in six rabbits, indicating that the CLR of azosemide is urine flow dependent in rabbits.

1. The urinary metabolites of sulphanilamide (100 mg/kg, i.p.) have been studied in four marsupials (the Tasmanian devil, brushtail possum, pademelon and barred bandicoot), a monotreme (the echidna) and a eutherian (the rat). 2. All species excreted some unchanged sulphanilamide (20-30% of dose in 24 h). The major urinary metabolite in the devil, possum and pademelon was N4-acetylsulphanilamide (6-17%). This was less than that excreted by the rat (40%). These three marsupials and the rat also excreted small amounts of N1-acetyl and N1, N4-diacetylsulphanilamide. 3. The bandicoot and echidna were virtually unable to acetylate sulphanilamide, unlike the 16 other species of animals and birds in which this has been studied. The reason for this metabolic defect is unknown.

During 1970-75 a total of 42 patients have been subjected to long-term treatment with procaine amide (PrA) because of different cardiac arrhythmias and have been observed up to over 5 years. Among these patients 35 (83%) developed a significantly increased titer of ANF and of these, 12 patients (29%) developed a "classical" drug-induced SLE syndrome. In the SLE group all but 2 improved rapidly after cessation of PrA, and the ANF titer decreased continuously but slowly in both groups. Acetylation test with sulphamidine and/or isoniazid in 11 patients among the SLE cases showed 8 slow and 3 fast acetylators. Among 12 patients who also had received PrA for a long time, but had not shown any signs of an SLE syndrome, there were 10 fast and 2 slow acetylators.

The extent of absorption of sulfanilamide, bretylium tosylate, sulfisoxazole acetyl, and riboflavin was determined in rats exposed to 850 rad of cobalt-60 gamma-radiation of sham irradiated. The drug were administered orally at 1 or 5 days postirradiation, and the amount of drug excreted in the urine was used as the measure of absorption. Following intravenous drug administration, there was no difference between irradiated and control animals in the amount of drug excreted in the urine. At 1 day postirradiation, the absorption of sulfanilamide and bretylium was not affected by radiation; the absorption of sulfisoxazole acetyl and riboflavin was increased. The fraction of sulfanilamide excreted in the urine as N4-conjugate was increased at 1 day postirradiation. At 5 days postirradiation, there was no detectable difference between irradiated and control animals in the extent of drug absorption. The effects of radiation on the extent of absorption of orally administered drugs were most pronounced immediately following irradiation. Irradiation apparently does not affect the absorption of drugs that are normally well absorbed or poorly absorbed due to slow transport across the GI mucosa. Following irradiation, there may be an increase in the extent of absorption of drugs that are poorly absorbed due to low aqueous solubility or that are absorbed by a saturable transport mechanism.

Lidaprim, a new bactericidal combination of trimethoprim and sulfametrol, was administered to 20 patients of a paediatric surgical ward over a period of 7 or more days. Analytic determination of plasma and urine concentrations of the chemotherapeutic agent showed homogeneous drug levels at the chosen dosage. No cumulation was observed. Drug tolerance was excellent. Only one patient developed urticaria when the substance was given together with penicillin, but it was not necessary to stop medication in this case.

A physiologically based model for drug reabsorption in renal tubules was applied to sulfanilamide reabsorption kinetics in rats, rabbits and dogs. The reabsorption percent of sulfanilamide decreased with an increase of urine flow rate in the three animal species examined. Furthermore, the reabsorption percent increased with the decrease of the glomerular filtration rate (GFR), even though the urine flow rate normalized by GFR was the same. The power law formula was obtained between AR (l) X Pe and the animal body weight. The power was 0.721, which was less than unity. In contrast, sigma was not dependent on animal body weight. The reabsorption percent of sulfanilamide in man was calculated using AR (l) X Pe and sigma obtained from animal data. The value thus calculated was 50-60%, which was comparable to the reported value (52%) in healthy human subjects. Therefore, the reabsorption percent of sulfanilamide in man was successfully predicted by the extrapolation of animal data.

Pharmacokinetic parameters of the long-term sulfanilamide Sulfaclomid (4-[4-aminobenzensulphonamido]2,6-dimethyl-5-chlorpyrimidine) were determined in 25 female subjects. Both the elimination half-life of Sulfaclomid in the serum and the maximum acetylation rate in the urine are genetically determined. They show a polymodal behavior. The half-life is unrelated to the protein binding, which shows considerable individual differences in the therapeutic relevant range of about 200 microgram/ml serum. This confirms the human pharmacological postulate according to pharmacokinetical dosage schedules including genetic factors. An individual therapy service is necessary in certain drugs and in highly endangered groups of patients.

The effect of probenecid on the plasma kinetics of sulfamonomethoxine (SMM) was examined in conscious pigs. A linear kinetic dose of SMM (10 mg/kg) was injected with or without probenecid. Probenecid (25 mg/kg, i.v.) was injected immediately before SMM injection and against at 1, 2, 3, 4 and 6 h later. The AUCs of SMM and of the acetylated compound of SMM (AcSMM) in probenecid injected animals were significantly larger when compared with those of non-injected animals (p less than 0.05). Next, possible active secretion from the renal tubule of SMM and its metabolites was examined using probenecid and pyrazinoate. Ten commercial pigs with ureter cannulae were used under anesthesia. The plasma concentration of SMM and AcSMM was maintained at a steady state by a priming dose of SMM (5 mg/kg, i.v.) followed by sustaining infusion (4 micrograms/kg/min). Renal clearance of AcSMM was suppressed by bolus injection of probenecid (25 mg/kg), but that of SMM was not. The renal excretion of a water soluble metabolite was suppressed by probenecid. No marked changes in renal excretory kinetics were found by pyrazinoate injection (12.5 mg/kg, i.v.). Consequently, the saturation in the active tubular secretion of AcSMM may play an important role in the nonlinear pharmacokinetics of SMM in pigs.

1. The metabolism of sulphanilamide, sulphadimidine (4,6-dimethyl-2-sulphanilamidopyrimidine), sulphamethoxazole (5-methyl-3-sulphanilamidoisoxazole) and sulphadoxine (5,6-dimethoxy-4-sulphanilamidopyrimidine) given by intravenous injection has been examined in cows. 2. The sulphonamides were present mainly as unchanged drugs in blood samples collected 2h after administration. 3. The sulphonamides were excreted in the milk partly as unchanged drugs and partly as conjugated metabolites whereas only small amounts were excreted as the N(4)-acetyl derivatives. 4. The unchanged drug and the N(4)-acetyl derivative were the major constituents in urine samples after administration of sulphanilamide, sulphamethoxazole and sulphadoxine. 5. Besides the unchanged drug, the N(4)-acetyl derivative and the conjugated metabolites, three further metabolites of sulphadimidine were isolated from urine samples and identified. They were 5-hydroxy-4,6-dimethyl-2-sulphanilamidopyrimidine, 4-hydroxymethyl-6-methyl-2-sulphanilamidopyrimidine and sulphaguanidine.

Lorapride has been determined in plasma, red blood cells, and urine by HPLC. The detection was performed at a short wavelength (226 nm), resulting in a detection limit of 10 ng/mL (amount injected was 3.5 ng). Reproducibility of analytical and chromatographic methods through statistical coefficients of variation was 4%. By TLC, only levels in urine were determined. Urine samples were spotted directly on the plate; lorapride was determined after spraying the plate with the Bratton-Marshall reagent, and measurements were carried out in the simultaneous reflectance and transmittance mode (540 nm). The detection limit was 10 ng spotted. Lorapride amounts in urine determined by the two methods were compared by statistical analysis. Examples of kinetics after intravenous and oral administration (100 mg) in humans are given.

A high-pressure liquid chromatographic method for the separation and quantitative determination of sulfamethazine, sulfathiazole, and their N4-acetylated metabolites on an amino-bonded reversed-phase column was developed. The method is suitable for the analysis of these compounds in pure solutions as well as in cattle urine. Retention times were reproducible. Injection volumes containing 0.2 mug of individual sulfonamides or their acetyl derivatives were successfully quantitated; coefficients of variation ranged from 0 to 0.073 for individual sulfonamides.

Sulfisomidine, sulfamethomidine, sulfadimethoxine and their corresponding N4-acetyl derivatives were administered to man. The percentages of acetylation and deacetylation and those of protein binding, the half-lives of elimination and the apparent and true renal clearance values were measured. No acetylation phenotype could be demonstrated in these compounds. Methoxy substitution in the NI-pyrimidine group of sulfisomidine affects predominantly the renal clearance value and mechanism of the parent compound but has no influence on the renal clearance of the N4-acetyl derivatives. The renal clearance value of sulfisomidine is 232 +/- 33 ml/min, of sulfamethomidine 21.60 +/- 16.4 ml/min and of sulfadimethoxine 10.87 +/- 10.44 ml/min. The renal clearance values of the corresponding N4-acetylsulfonamide derivatives are 314 +/- 91 ml/min, 342 +/- 63 ml/min and 202 +/- 65 ml/min respectively. Tubular reabsorption, caused by methoxy substitution in the NI-pyrimidine ring, lowers the rate of elimination and increases the half-life. The half-life of sulfisomidine is 8.5 +/- 0.5 h, of sulfamethomidine 27.8 +/- 5.3 h and of sufadimethoxine 34.6 +/- 10.4 h.