Bismuth In Urine Research Articles

Bismuth Toxicity Presenting as Declining Mobility and Falls.

A 77-year old woman presented with a history of falls. Known health problems included biopsy-proven collagenous colitis treated with bismuth subsalicylate. On examination, in addition to impaired balance and gait, she was found to have tremors and cognitive deficits. Investigations revealed a markedly elevated urinary bismuth level. Withdrawal of bismuth subsalicylate led to marked cognitive and physical improvement.

Multivariate optimization of a digestion procedure for bismuth determination in urine using continuous flow hydride generation and atomic fluorescence spectrometry

A sensitive method has been developed for the determination of bismuth in urine using continuous flow hydride generation and atomic fluorescence spectrometry (HG AFS). The conditions for bismuth hydride generation as well as some instrumental parameters were optimized using univariate methodology. Experimental conditions for sample digestion using nitric acid, hydrogen peroxide and a reflux system by “cold finger” were optimized employing a two-level full factorial design and a Box-Behnken design. Nitric acid used during sample preparation showed a negative effect on Bi determination by HG AFS, and a drying step was required after digestion. The established conditions for sample digestion allowed a low residual carbon content. Thus, the proposed method, using 5mL urine, allowed bismuth determination with limits of detection and quantification of 0.02 and 0.08μgL−1, respectively. Accuracy was assessed by the spike/recovery test using urine samples and the recoveries obtained varied from 91and 97%. Precision expressed as relative standard deviation (RSD) was lower than 10%. This method was satisfactorily applied for the determination of bismuth in five urine samples. The bismuth contents found ranged from 0.30 to 0.66μgL−1.

Adsorption and Preconcentration Capabilities of Nano-Barium-Strontium Titanate Powder Coated by Dithizone for Trace Bismuth

A new method for the adsorption and preconcentration of bismuth in urine was described. The methodology combines determined using a hydride generation-atomic absorption spectrometry (HG-AAS) with pre-concentration and separation of the bismuth on the nano-barium-strontium titanate powder coated by dithizone (BST-dithizone). The experimental conditions for the pre-concentration and separation of the bismuth, including pH value of the medium, shaking time, eluent condition and co-existing ions have been investigated. The result showed that the bismuth in urine could be adsorbed on the BST-dithizone. The adsorption percentage was affected by the pH value of medium and shaking time. In the medium of pH 6.0, the adsorption capacity of BST-dithizone to bismuth (III) was 13.4 mg·g-1 when the shaking time was 10 min. The bismuth adsorbed on the BST-dithizone could be completely eluated by 2 mol·L-1 HNO3. The enrichment factor was 100. The detection limit of bismuth (III) was 5.1 ng·L−1.The method has been applied to the pre-concentration and separation of bismuth in the human urine and tap water with satisfied results.

Determination of Trace Bismuth in Urine and Tap Water Samples by Atomic Absorption Spectrometry after Solid-Phase Extraction

In this paper, a new method for the determination of bismuth in urine and tap water is described. The methodology combines determined using a hydride generation-atomic absorption spectrometry (HG-AAS) with pre-concentration of the bismuth on the modified organobentonite by dithizone (D-O-bentonite). Optimal experimental conditions for the adsorption and elution of the bismuth, including pH, contact time, eluent concentration, eluent volume and co-existing ions have been investigated. The result showed that the bismuth ion could be adsorbed on the D-O-bentonite. The adsorbed quantitive was affected by the pH value and contact time. In the medium of pH 5.0, the shaking time was 10 min, the adsorption capacity was 15.2 mg·g-1. The bismuth adsorbed on the modified organobentonite by dithizone could be completely eluated by using 2 mol·L-1 HNO3. The method has been applied to the pre-concentration/separation of bismuth in the human urine and tap water samples with satisfied results.

Cloud point extraction spectrophotometric determination of trace quantities of bismuth in urine

A cloud point extraction process using the nonionic surfactant Triton X-114 to extract bismuth from aqueous solutions was investigated. The method is based on the complexation reaction of Bi(III) with bromopyrogallol red (BPR) and micelle-mediated extraction of the complex. The optimal extraction and reaction conditions (e.g., pH, reagent concentration, effect of time) were studied, and the analytical characteristics of the method (e.g., limit of detection, linear range) were obtained. Linearity was obeyed in the range of 4.60-120.0 ng mL-1 of Bi(III) ion. The detection limit of the method was 2.0 ng mL-1 of Bi(III) ion. The interference effect of some anions and cations was also tested. The method was applied to the determination of bismuth in human urine sample.

Flow injection determination of bismuth in urine by successive retention of Bi(III) and tetrahydroborate(III) on an anion-exchange resin and hydride generation atomic absorption spectrometry

Bismuth as BiCl 4 − and BH 4 − ware successively retained in a column (150 mm × 4 mm, length × i.d.) packed with Amberlite IRA-410 (strong anion-exchange resin). This was followed by passage of an injected slug of hydrochloric acid resulting in bismuthine generation (BiH 3). BiH 3 was stripped from the eluent solution by the addition of a nitrogen flow and the bulk phases were separated in a gas–liquid separator. Finally, bismutine was atomized in a quartz tube for the subsequent detection of bismuth by atomic absorption spectrometry. Different halide complexes of bismuth (namely, BiBr 4 −, BiI 4 − and BiCl 4 −) were tested for its pre-concentration, being the chloride complexes which produced the best results. Therefore, a concentration of 0.3 mol l −1 of HCl was added to the samples and calibration solutions. A linear response was obtained between the detection limit (3 σ) of 0.225 and 80 μg l −1. The R.S.D.% ( n = 10) for a solution containing 50 μg l −1 of Bi was 0.85%. The tolerance of the system to interferences was evaluated by investigating the effect of the following ions: Cu 2+, Co 2+, Ni 2+, Fe 3+, Cd 2+, Pb 2+, Hg 2+, Zn 2+, and Mg 2+. The most severe depression was caused by Hg 2+, which at 60 mg l −1 caused a 5% depression on the signal. For the other cations, concentrations between 1000 and 10,000 mg l −1 could be tolerated. The system was applied to the determination of Bi in urine of patients under therapy with bismuth subcitrate. The recovery of spikes of 5 and 50 μg l −1 of Bi added to the samples prior to digestion with HNO 3 and H 2O 2 was in satisfactory ranges from 95.0 to 101.0%. The concentrations of bismuth found in six selected samples using this procedure were in good agreement with those obtained by an alternative technique (ETAAS). Finally, the concentration of Bi determined in urine before and after 3 days of treatment were 1.94 ± 1.26 and 9.02 ± 5.82 μg l −1, respectively.

The use of a W-Rh permanent modifier for direct determination of bismuth in urine and whole blood by electrothermal atomic absorption spectrometry

The direct determination of bismuth in urine and whole blood samples is proposed by graphite furnace atomic absorption spectrometry. The pyrolytic integrated platform of the THGA tube was coated with 250 µg W + 200 µg Rh to increase the tube lifetime. Urine samples were diluted (1 + 1 v/v) and blood samples (1 + 4 v/v) in a solution containing 1.0% v/v HNO3 + 0.2% Triton X-100, and 20 µl of the resulting dilute samples were delivered into the W-Rh modified platform together with 10 µl of 10 mg l−1 Rh solution. After 350 firings a new coating was made. The combined use of Rh solution with the W-Rh coating was decisive for increasing the maximum pyrolysis temperature of blood and urine bismuth up to 1100 °C. With this approach the tube lifetime increased by 80% and re-calibrations were minimised when compared to a Pd + Mg conventional modifier. The detection limits (n = 20) were 3.3 µg l−1 and 8.4 µg l−1 for urine and whole blood, respectively, and the characteristic mass was 49.0 pg using standard THGA. The accuracy of the proposed method was verified by comparing the results with the decomposed sample solutions. No statistical differences were found by the paired t-test at the 99% confidence level.

Determination of bismuth in urine and prescription medicines using atomic absorption with an on-line hydride generation system.

The bismuth contents of various digested urine samples and prescription medicines were determined by atomic absorption spectrometry combined with hydride generation. The procedure followed was a standard addition method for urine and direct calibration for the prescription medicines. The detection limit of the method was determined to be 320 pg ml-1 Bi with an analytical frequency of 150 h-1. A relative standard deviation of 4.7% was found for Bi in urine at the level of 4.3 ng ml-1 Bi. Interference caused by NiII, CoII, CuII, AgI, SeIV, SbIII and HgII could be controlled with a masking solution of thiourea (0.2%)-KI (10%).

Plasma and tissue distribution of bismuth in normal and cirrhotic rats.

The effect of liver disease on total body handling of bismuth was studied in normal and cirrhotic rats to test the hypothesis that hepatic function can be a significant determinant of heavy metal handling. Excretion and tissue distribution of bismuth were investigated in animals administered bismuth subcitrate by the intramuscular route for 70 d. Plasma bismuth in control rats reached an apparent steady state of 31.89 +/- 4.15 micrograms l-1 (mean +/- standard error of mean, n = 12) by day 28-35. The plasma profile in cirrhotic rats resembled that of controls until day 42 after which bismuth concentrations became significantly elevated. At day 70 of dosing the mean plasma bismuth concentration was 63.68 +/- 9.68 micrograms l-1 (n = 11) in cirrhotic rats compared with 32.68 +/- 4.24 micrograms l-1 (n = 12) in control rats (p < 0.05). Total urinary excretion of cirrhotic animals closely paralleled that of controls; however, urinary bismuth clearance was significantly reduced beyond 42 d, as was faecal excretion. Bismuth tissue distribution was analysed in a randomly selected sub-set of control and cirrhotic animals. There was a significantly higher concentration of bismuth in the liver, bone, spleen, lungs and heart of the cirrhotic rats, with no change in the kidney. There was minimal accumulation of bismuth in the central nervous system of either normal or cirrhotic animals. Bismuth accumulation in cirrhotic rats suggests that patients with cirrhosis could be at risk from similar accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of evidence of neurotoxicity following 8 weeks of treatment with tripotassium dicitrato bismuthate

To search for evidence of subclinical neurotoxicity in patients treated with tripotassium dicitrato bismuthate. Prospective, controlled, triplicate study using urinary bismuth concentration, magnetic resonance imaging (MRI), nerve conduction studies, visual evoked response and a battery of 10 neuropsychological screening tests. Out-patient clinics, Walsgrave Hospital, Coventry, UK. Fourteen dyspeptic patients; 8 (treatment group) treated with tripotassium dicitrato bismuthate one tablet q.d.s and 6 (control group) treated with ranitidine 150 mg b.d. for 8 weeks. Changes in urinary bismuth, MRI, nerve conduction studies, visual evoked response, and neuropsychological tests performed before, immediately after and 8 weeks after the cessation of treatment. In the treatment group the median (range) urinary bismuth concentration was 1 (1-12) ng/ml before treatment, increased to 560 (140-1300) immediately after treatment (P < 0.01, Wilcoxon Rank Sum test) and was still significantly elevated (23 (7-53) ng/ml) 8 weeks after the cessation of treatment. In the patient who recorded the highest urinary bismuth, a high intensity signal appeared in the globus pallidus immediately after treatment and was still present (though diminished in intensity) 8 weeks after the cessation of treatment. This isolated MRI finding was not associated with evidence of subclinical neurotoxicity. No changes in the MRI, nerve conduction studies, visual evoked response and neuropsychological tests were observed among the other patients studied. Bismuth accumulation occurs in patients receiving a conventional course of treatment with tripotassium dicitrato bismuthate but this is not associated with significant changes in the nervous system.

The effect of histamine H2-receptor blockade on bismuth absorption from three ulcer-healing compounds

Twelve healthy male subjects were dosed with six regimens: ranitidine and De-Noltab (tripotassium dicitrato bismuthate; Gist-Brocades Ltd., Weybridge, England), placebo and De-Noltab, ranitidine and Pepto-Bismol liquid [bismuth salicylate; Procter & Gamble (Health and Beauty Care) Ltd., Egham, England], placebo and Pepto-Bismol, ranitidine and Roter tablets (bismuth subnitrate; Roter Pharma Ltd., Ashford, England), and placebo and Roter. Ranitidine, 300 mg, or placebo was administered at 10 pm (night before) and at 7 am; at 9 am, the oral dose of bismuth was either 2 De-Noltabs, 3 30-mL doses of Pepto-Bismol liquid, or 2 Roter tablets. When predosed with placebo, the median integrated 8-hour plasma bismuth concentration was significantly greater after dosing with De-Noltabs than after dosing with either Pepto-Bismol or Roter (61, 8, and 8 ng · h/mL, respectively), with a similar trend for 8-hour median urinary bismuth excretion (213, 40, and 6 μg, respectively). When predosed with ranitidine, only after De-Noltab administration were there significant increases in the 8-hour plasma bismuth concentration (147 ng · h/mL), and 8-hour urinary bismuth excretion (686 μg). Eliminating intragastric acidity may enhance bismuth absorption after oral dosing with De-Noltabs by maintaining intragastric tripotassium dicitrato bismuthate as a colloidal suspension.

The effect of GR122311X, a bismuth compound with H2‐antagonist activity, on 24‐hour intragastric acidity

GR122311X (ranitidine bismuth citrate Glaxo Group Research Ltd) is a bismuth compound with histamine H2-receptor antagonist activity. The gastric acid antisecretory activity of three oral dosage regimens of GR122311X was compared with placebo and 150 mg ranitidine b.d. The median 24-h integrated intragastric acidity was 38, 26 and 18% of the median placebo value during dosing with GR122311X 196, 391 and 782 mg b.d., respectively. The 24-h acid suppression with GR122311X 391 mg b.d. was not significantly different to that produced by 150 mg ranitidine b.d. (24% of placebo acidity). The median 24-h urinary bismuth excretion increased with rising dosage of GR122311X from 19.2 micrograms with 196 mg b.d., to 36.4 micrograms with 391 mg b.d., to 68.7 micrograms with 782 mg b.d. In conclusion, GR122311X is an effective antisecretory agent with modest systemic bismuth absorption.

D‐penicillamine does not increase urinary bismuth excretion in patients treated with tripotassium dicitrato bismuthate.

Twenty-four urinary bismuth excretion was measured in five patients who had been treated with tripotassium dicitrato bismuthate, before and after single 1 g oral dose of D-penicillamine. Before dosing with D-penicillamine, the median 24 h urinary bismuth output was 55 micrograms 24 h-1 (range 17-156 micrograms 24 h-1) and following dosing with D-penicillamine the median 24 h urinary bismuth output was 53 micrograms 24 h-1 (range 12-156 micrograms 24 h-1). D-penicillamine does not facilitate the urinary excretion of bismuth, hence it is unsuitable for use as an oral chelator in patients with bismuth intoxication.

The absorption of bismuth from oral doses of tripotassium dicitrato bismuthate

Two studies measured plasma concentrations of bismuth during dosing with tripotassium dicitrato bismuthate (De-Noltab). The first study compared 24 h plasma bismuth concentration and urinary bismuth excretion in six patients who had already received 29-131 days (median 47 days) of treatment with De-Noltab 2 b.d., and six healthy subjects who only received De-Noltab 2 b.d. on the day of study. There was a prompt rise in plasma bismuth concentration after each dose of De-Noltabs. The median 24 h integrated plasma bismuth concentration was similar in both groups, but the median 24 h urinary bismuth excretion was 5.4-fold higher in the patients. The second study compared the plasma bismuth concentrations after the first and third doses of De-Noltab 2 b.d. in 16 healthy subjects. The median peak bismuth concentration occurred 30 min (range 15-105 min) post-dosing. The peak plasma bismuth concentration was greater than 50 ng/ml in 14 of the 16 subjects, and greater than 100 ng/ml in nine of the subjects. There was no significant difference in the median integrated 10-h plasma bismuth concentration after the first or third dose of De-Noltabs. The results of these studies confirm that bismuth is absorbed and sequestrated during dosing with De-Noltabs. Bismuth is absorbed rapidly after oral dosing with De-Noltabs, to produce peak plasma bismuth concentrations hitherto considered to be in the range associated with bismuth neurotoxicity.

Bismuth accumulates in the body during treatment with tripotassium dicitrato bismuthate

Bismuth concentration was measured in plasma, dried leucocytes and urine in nine patients before, during and after treatment with tripotassium dicitrato bismuthate (De-Noltab 2 b.d.) for 6 weeks. During treatment there was an 8.5-fold rise in median plasma bismuth concentration (P less than 0.01), a non-significant doubling of leucocyte bismuth content, and a 349-fold rise in 24-h urinary bismuth excretion (P less than 0.01). The significantly increased urinary bismuth excretion continued for at least 3 months after cessation of treatment with tripotassium dicitrato bismuthate, indicating accumulation of bismuth during treatment with this drug.

Determination of bismuth in urine by atomic absorption with hydride generation.

A procedure for the determination of urinary bismuth by atomic absorption spectroscopy with hydride generation was developed and evaluated. Specimen or standard solutions were mixed with an acid mixture and an antifoam reagent. Sodium borohydride solution was then introduced to the reaction flask in order to produce bismuth hydride. The preliminary reference range for urinary bismuth was found to be less than 17 micrograms/L in 20 healthy control subjects. For patients on medications or medical treatments, bismuth levels varied from 5 to 1,460 micrograms/L. The minimum detection limit was found to be 2.5 micrograms/L and the procedure was linear to 250 micrograms/L. The intra-assay and interassay coefficients of variation at the level of 21 micrograms/L were 4.0 (N = 33) and 4.1% (N = 19), respectively. Average bismuth recovery was 97.7% for concentrations ranging from 25 to 100 micrograms/L. This procedure is simple, fast, and sensitive enough to detect levels well into the reference range. Preliminary studies also indicate this method can be used for serum bismuth determinations.

Effects of tripotassium dicitrato bismuthate (TDB) tablets or cimetidine in the treatment of duodenal ulcer.

Forty patients with duodenal ulcer were randomly allocated to treatment with either tripotassium dicitrato bismuthate tablets or cimetidine for six weeks. Endoscopically confirmed healing of the ulcer occurred in 80% treated with tripotassium dicitrato bismuthate tablets and in 85% treated with cimetidine. Symptomatic improvement was also similar in the two groups. Treatment with cimetidine was associated with an increase in pH of gastric aspirate during treatment and increased numbers of bacteria were isolated from the gastric aspirate during treatment, while the pH and bacterial flora of gastric aspirate did not change during tripotassium dicitrato bismuthate treatment. Serum and urinary bismuth levels rose during treatment with tripotassium dicitrato bismuthate and urinary excretion remained raised two weeks after cessation of treatment. Tripotassium dicitrato bismuthate tablets appear to be as effective as cimetidine in the treatment of duodenal ulcer without the potentially undesirable effects of a reduction in gastric acid secretion.

A Rapid Determination of Trace Amounts of Bismuth in Urine and Blood Using Differential Pulse Anodic Stripping Voltammetry at the Hanging Mercury Electrode

Abstract Bismuth in 5 ml of blood or 10 ml of urine is determined by dilution to 100 ml with 0.25 M HCl, separation by anion exchange chromatography (Amberlite IRA-400 (Cl)), and measurement by differential pulse anodic stripping voltammetry in the presence of 0.1 M KCl.

Determination of bismuth in blood and urine.

Bismuth is determined in blood and urine by means of atomic-absorption spectrophotometry following generation of bismuth hydride from a wet-oxidised sample. Recoveries are shown to be satisfactory, and the detection limit using analytical-reagent grade reagents is less than 0.01 µg ml–1.The direct determination of bismuth in urine by means of hydride generation has been investigated, and it is shown that there is severe suppression and poor recovery.

Determination of bismuth content of urine. Polarographic method

A polarographic method for the determination of bismuth in urine is described. A preliminary purification of the sample by means of ion-exchange resins in order to eliminate interfering matter, is proposed. Several tests carried out on samples of urine with different bismuth contents, have shown that it is possible to determine the bismuth content of urine in micrograms per milliliter with a 2% margin of error.