Electrocatalytic response of poly(cobalt tetraaminophthalocyanine)/multi-walled carbon nanotubes-Nafion modified electrode toward sulfadiazine in urine.

A highly sensitive amperometric sulfadiazine sensor fabricated by electrochemical deposition of poly(cobalt tetraaminophthalocyanine) (poly(Co(II)TAPc)) on the surface of a multi-walled carbon nanotubes-Nafion (MWCNTs-Nafion) modified electrode is described. This electrode showed a very attractive performance by combining the advantages of Co(II)TAPc, MWCNTs, and Nafion. Compared with the bare glassy carbon electrode (GCE) and the MWCNTs-Nafion modified electrode, the electrocatalytic activity of poly(Co(II)TAPc)-coated MWCNTs-Nafion GCE generated greatly improved electrochemical detections toward sulfadiazine including low oxidation potential, high current responses, and good anti-fouling performance. The oxidation peak currents of sulfadiazine obtained on the new modified electrode increased linearly while increasing the concentration of sulfadiazine from 0.5 to 43.5 µmol/L with the detection limit of 0.17 µmol/L.

A novel chemiluminescence quenching method for determination of sulfonamides in pharmaceutical and biological fluid based on luminol-Ag(III) complex reaction in alkaline solution.

A novel chemiluminescence (CL) quenching method for the determination of sulfonamides is proposed. The CL reaction between Ag(III) complex [Ag(HIO6)2]5⁻ and luminol in alkaline solution was investigated. The quenching effect of sulfonamides on CL emission of [Ag(HIO6)2]5⁻-luminol system was found. Quenching degree of CL emission was proportional to sulfonamide concentration. The effects of the reaction conditions on CL emission and quenching were examined. Under optimal conditions, the detection limits (s/n = 3) were 7.2, 17 and 8.3 ng/mL for sulfadiazine, sulfameter, and sulfadimethoxine, respectively. The recoveries of the three drugs were in the range of 91.3-110% with RSDs of 1.9-2.7% for urine samples, and 106-112% with RSDs of 1.6-2.8% for serum samples. The proposed method was used for the determination of sulfadiazine at clinically relevant concentrations in real urine and serum samples with satisfactory results.

Flow-injection spectrophotometric determination of sulfadiazine and sulfamethoxazole in pharmaceuticals and urine.

A rapid and sensitive flow-injection spectrophotometric method is proposed for the determination of sulfadiazine and sulfamethoxazole. This method is based on the diazotization of sulfonamide with sodium nitrite, and a coupling reaction of the diazo-compound with alpha-naphthylamine. The optimum experimental conditions are obtained by using the controlled and weighted centroid simplex method. The linear ranges for the determination of sulfadiazine and sulfamethoxazole are 0.2-20 microg ml(-1) and 0.1-20 microg ml(-1), and their detection limits are 0.06 microg ml(-1) and 0.05 microg ml(-1), respectively, and the sampling frequency is 130 samples per hour. The method has been used to determine sulfadiazine and sulfamethoxazole in pharmaceuticals and urine without separation. The results are in agreement with those obtained by a high-performance liquid chromatograph technique at the 95% confidence level.

Effect of sulfadiazine and pyrimethamine on selected physiologic and performance parameters in athletically conditioned thoroughbred horses during an incremental exercise stress test.

Following the regimen used to treat equine protozoal myeloencephalitis, sulfadiazine (20 mg/kg) and pyrimethamine (1mg/kg) were administered orally once daily to 12 physically conditioned Thoroughbred horses for 4 consecutive days. The horses were randomly assigned to two test groups in a crossover design, with each horse serving as its own control. A stepwise exercise stress test was conducted to exhaustion. No effect on athletic performance was observed, and only marginal effects were noted in some hematologic and serochemical measurements, including decreased total white blood cell counts, red blood cell distribution width, total hemoglobin, serum sodium, and serum chloride. Serum folic acid concentration decreased significantly following sulfadiazine/pyrimethamine treatment.

Determination of sulfadiazine and sulfamethoxazole by capillary electrophoresis with end-column electrochemical detection.

Capillary electrophoresis (CE) with end-column electrochemical detection (EC) of sulfadiazine (SDZ) and sulfamethoxazole (SMZ) is described. Under the optimum conditions, SDZ and SMZ were separated satisfactorily, and a highly sensitive and stable response was obtained at a potential of 1.1 V versus Ag/AgCl. Optimized end-column detection provides detection limits as low as 0.1 microM for both compounds, which corresponds to 0.024 and 0.021 fmol with peak efficiencies of 394,000 and 335,000 theoretical plates for SDZ and SMZ, respectively. The calibration graph was linear over three order of magnitude. The relative standard deviations (n = 12) of peak currents and migration times were 2.3 and 2.7%, and 0.8 and 1.3%, respectively, for the two compounds. The proposed method was applied to the analysis of tablets and human urine samples with satisfactory results.

Acute renal failure due to sulphadiazine crystalluria in AIDS patients.

We report two AIDS patients who developed acute renal failure while receiving sulphadiazine for cerebral toxoplasmosis. Renal ultrasound revealed diffuse bilateral echogenic shadowing material. 'Sheaves of wheat' crystals, typical of sulphadiazine crystalluria, were present in the urine. One patient required a percutaneous nephrostomy. Hydration and urine alkalinisation resulted in rapid improvement of renal function and ultrasonographic findings. Sulphadiazine-induced crystalluria and acute renal failure is increasingly frequent. Awareness of its existence may lead to prevention and early conservative treatment.

Improved determination of sulfadiazine in human plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of sulfadiazine in human plasma and human urine was developed and validated. The method involves the acid extraction of drug and internal standard from plasma with ethyl acetate followed by evaporation and reconstitution in mobile phase. Urine samples were simply diluted with purified water. Recovery, linearity, intra- and inter-day variation of sulfadiazine were tested and found appropriate. The quantitation range was 0.0299-15.2 micrograms/ml for plasma samples and 0.578-148.8 micrograms/ml for urine samples. The method is suitable for the quantitation of sulfadiazine from pharmacokinetic studies.

Isolation, identification and determination of sulfadiazine and its hydroxy metabolites and conjugates from man and rhesus monkey by high-performance liquid chromatography.

The following metabolites of sulfadiazine (S) were isolated from monkey urine by preparative HPLC: 5-hydroxysulfadiazine (5OH), 4-hydroxysulfadiazine (4OH) and the glucuronide (5OHgluc) and sulfate conjugate of 5OH (5OHsulf). The compounds were identified by NMR, mass and infrared spectrometry and hydrolysis by beta-glucuronidase. The analysis of S, the hydroxymetabolites (4OH, 5OH) and conjugates N4-acetylsulfadiazine (N4), 5OHgluc and 5OHsulf in human and monkey plasma and urine samples was performed using reversed-phase gradient HPLC with UV detection. In plasma, S and N4 could be detected in high concentrations, whereas the other metabolites were present in only minute concentrations. In urine, S, the metabolites and conjugates were present. The limit of quantification of the compounds in plasma varies between 0.2 and 0.6 microgram/ml (S 0.31, N4 0.40, 4OH 0.20, 5OH 0.37, 5OHgluc 0.33 and 5OHsulf 0.57 microgram/ml). In urine it varies between 0.6 and 1.1 micrograms/ml (S 0.75, N4 0.80, 4OH 0.60, 5OH 0.80, 5OHgluc 0.80 and 5OHsulf 1.1 micrograms/ml). The method was applied to studies with healthy human subjects and Rhesus monkeys. The metabolites 5OH, 5OHgluc and 5OHsulf were present in Rhesus monkey and not in man. Preliminary results of studies of metabolism and pharmacokinetics in Rhesus monkey and man are presented.

Pharmacokinetics and urinary excretion of sulfadiazine in buffalo calves.

Pharmacokinetics and urinary excretion of sulfadiazine were determined in buffalo calves following single oral administration (150 mg/kg). Kinetic evaluation of plasma levels was performed using a 2-compartment model. The absorption half-life and elimination half-life were 3.41 +/- 0.63 and 13.75 +/- 1.94 h, respectively. Based on this study, an optimal dosage regimen of sulfadiazine in buffalo calves would be 165 mg/kg, followed by 75 mg/kg at 12-h intervals. Sulfadiazine was mainly excreted in the urine as free amine, while the percentage of acetylated sulfadiazine was comparatively low.

High performance liquid chromatographic analysis of tetroxoprim and sulphadiazine in serum and urine.

Quantitative determination of tetroxoprim and sulphadiazine in serum and urine was performed using reversed phase high performance liquid chromatography. Protein precipitation using 10% perchloric acid was utilized for purification of serum samples while urine samples were diluted prior to analysis. The mobile phase consisted of triethylammonium acetate buffer (85%), acetonitrile (12%) and methanol (3%), with a final pH of 4.2. The eluent was monitored at 280 nm. Benzoic acid was used as an internal standard. Standardization, validation and application of the method is described.

Sulfadiazine-induced crystalluria in AIDS patients with toxoplasma encephalitis.

Toxoplasma encephalitis is the most common opportunistic infection of the central nervous system in patients with AIDS. The treatment of choice is a combination of sulfadiazine and pyrimethamine. We present here four patients with AIDS treated for toxoplasmic encephalitis who developed sulfadiazine-induced crystalluria. This complication was rapidly reversible with rehydration and urine alkalinization. Patients with AIDS treated with high doses of sulfadiazine should be adequately hydrated, and their urinary pH maintained above 7.5 to prevent sulfadiazine-induced crystalluria.

HPLC determination of tetroxoprim and sulphadiazine in pharmaceutical dosage forms and in biological fluids.

Two HPLC methods for determination of tetroxoprim and sulphadiazine in pharmaceutical dosage forms and in biological fluid are reported. Both methods show good linearity, precision, accuracy and reproducibility. The serum levels and urinary excretion of tetroxoprim and sulphadiazine in man, after oral administration of two different syrup formulations, are reported. Tetroxoprim embonate, an insoluble salt very useful for obtaining a suspension with good palatability, shows a bioavailability not statistically different from that of tetroxoprim base. Sulphadiazine shows the same bioavailability in the two syrups.