Urine platinum

The body excretes platinum in various ways, mainly through urine the complex Pt(L-methionine-SN)2 is one of the few characterized products [206]. 

Conductometric transducers, as the oldest electrochemical devices, seem not to enjoy wide applications due to their poor selectivity. For example, Yagiuda et al. proposed a conductometric immunosensor for the determination of methamphetamine (MA) in urine [89], The decrease in the conductivity between a pair of platinum electrodes might result from the direct attachment of MA onto the anti-MA antibodies immobilized on the electrode surface. The system was claimed to be a useful detection technique of MA in comparison with a gas chromatography-mass spectrometry method. 

A number of workers have described methods for the determination of mercury in which the mercury is first reduced to the element or collected as the sulfide on a cadmium sulfide pad. It is then volatilized into a chamber for measurement. These techniques are extremely sensitive. Thillez108) recently described a procedure for urinary mercury in which the mercury is collected on platinum and then volatilized into an air stream. Rathje109) treated 2 ml of urine with 5 ml of nitric acid for 3 min, diluted to 50 ml, and added stannuous chloride to reduce the mercury to the element. A drop of Antifoam 60 was added and nitrogen was blown through the solution to carry the mercury vapor into a quartz end cell where it is measured. Six nanograms of mercury can be detected. Willis 93) employed more conventional methods to determine 0.04 ppm of mercury in urine by extracting it with APDC into methyl-n-amyl ketone. Berman n°) extracted mercury with APDC into MIBK to determine 0.01 ppm. 

Such high maintenance of cytotoxic activity in the in vitro serum medium and long in vivo circulation of Pt in the blood for DCM-Dex/CDDP conjugate were due to the strength of six-membered chelate-type coordination of the platinum atom with carrier polymer and steric hindrance of carrier polymer. Summarized in Table 2 are the results of the compartment model analysis. The show excretion rate of the Pt complex into urine by the DCM-Dex/CDDP conjugate compared with rapid excretion by the free CDDP in rats supported the longer circulation time for the Pt polymer complex in the blood (Figure 3). 

The active Pt(IV) compounds are octahedrally coordinated and possess axial bound chloride or—to improve the solubility—hydroxo ligands, i.e., two Y ligands in the trans orientation. These compounds are far more inert than the corresponding Pt(II) compounds that lack these axial ligands. Most likely the Pt(IV) compexes are reduced in vivo to the corresponding Pt(II) complexes, which are in fact the active species (17-19). They can therefore be considered as a type of prodrug that requires in vivo activation (substitution and reduction) to the square-planar Pt(II) compounds to exhibit antineoplastic activity. This hypothesis is supported by the observation that platinum(IV) compounds are unable to react with DNA under ambient conditions (19), and that appreciable amounts of Pt(II) derivatives can be detected in the urine of Pt(IV)-treated patients(fS). 

The reaction of sulfur-containing biomolecules with platinum antitumor compounds, thereby preventing binding to the critical DNA target, is a possible mechanism of inactivation and is supported by numerous studies. Thus, glutathione (GSH, a cysteine-containing tripeptide see also Fig. 6), which is the predominant intracellular thiol and is present in concentrations varying from 0.5 to 10 mM, is able to inhibit the reaction of DNA with [Pt(en)Cl2] (74) and with cis-Pt (75, 76). It has also been observed that the presence of cysteine can inhibit the reaction between cis-Pt and d-Guo (77). Furthermore, the antitumor activity of cis-Pt was proved to be inhibited by coadministered methionine (78, 79) and even a bis-adduct between cis-Pt and methionine has been isolated from the urine of patients (80). 

Reference ranges have been established for arsenic, lead, cadmium, mercury, platinum, nickel in blood and urine pentachlorophenol and metabolites of organophosphorus in serum and urine PCBs, fi-HCH, HCB, DDE in blood organochlorine pesticides (fi-HCH, HCB, total DDT) in human milk... 

Of the platinum-based drugs, cisplatin or cf -diarnmincdichloroplatinum (II) has been the most studied in treatments of cancerous tumours. Quantities of the drug administered in treatments must be carefully controlled because of appearances of side effects, primarily nephrotoxicity and nausea in patients. In some studies, ultrafilterable cisplatin, or free platinum in blood serum or plasma has been differentiated from platinum bound to proteins (Goel et al., 1990). HPLC has been used extensively in separations of intact cisplatin from other species. An anion-exchange column was connected to a post-column reactor and a UV-spectrophotometer for measurements of cisplatin concentrations in plasma and urine (Kizu et al., 1995). The detection limit was 20 nmol dm-3. Modes of action... 

Flow-injection analysis is a versatile technique to evaluate the performance of a detector system. CHEMFETs may have an advantage over ISEs because of their small size and fast response times. We have tested our K+-sensitive CHEMFETs in a wall-jet cell with a platinum (pseudo-)reference electrode. One CHEMFET was contineously exposed to 0.1 M NaCl and the other to a carrier stream of 0.1 M NaCl in which various KC1 concentrations in 0.1 M NaCl were injected. The linear response of 56 mV per decade was observed for concentrations of KC1 above 5 x 10"5 M (Figure 9). When we used this FIA cell (Figure 10) for determination of K+ activities in human serum and urine samples, excellent correlations between our results and activities determined by flame photometry were obtained (Figure 11). 

Exposure to chromium(VI) can result in DNA-protein complexes, the identification of which may be useful as biomarkers of exposure to chromates (Costa 1991). Gel electrophoresis and immunochemical techniques were used to identify actin as the protein in a DNA-protein complex induced by potassium chromate in cultured Chinese hamster ovary cells. While the DNA-protein complexes induced by formaldehyde and ultraviolet light were different from those induced by chromate, actin was also identified as the protein in the complex induced by cis-platinum, indicating that the DNA-actin complex is not specific for chromium. However, an experiment in a group of four volunteers did not demonstrate an increase in DNA-protein crosslinks in leukocytes over a 240 minute period following the ingestion of 5 mg chromium(VI) as potassium dichromate in a 10 mg chromium/L solution or the same amount added to 300 mL of orange juice (presumably reducing chromium(VI) to chromium(III)) and diluted to 500 mL with deionized water (Kuykendall et al. 1996). Chromium levels in red cells, plasma and urine were increased. In a separate experiment in this study, a threshold dose of 52 pg chromium(VI)/L was determined for crosslink formation in cultured lymphoma cells. 

Platinum speciation using IPC-ICP-MS has been achieved by Zhao et al. [50], An ODS C18 column and 1-heptanesulfonate ion-pairing reagent at pH 2.6 were used to separate the metabolites of cisplatin and cisplatin hydrolysis products. The low pH was required in order to retain thiol containing complexes. All complexes were resolved and urine and blood samples were analyzed by the speciation method. 

Tissue distribution studies in mice revealed that, 48 h after 200 mg/kg oral administration of JM216, platinum levels were the highest in the liver (6-19 pg Pt/g tissue) and kidney (2.8-12 pg Pt/g tissue). This is 5 times higher than that which has been reported after equivalent doses of cisplatin. All other tissues (spleen, heart, lung) had levels <3.1 pg Pt/g tissue. In the liver a time course of platinum levels showed that the Cmax were reached by 2 hpost administration [22], Following administration of 200 mg/kg JM216 orally (in oil or in saline) 8% of platinum was eliminated in urine over 72 h and 66% was present in the faeces after 72 h. 

J. Begerow, M. Turfeld, L. Dunemann, Determination of physiological palladium and platinum levels in urine using double focusing magnetic sector held ICP-MS, Frese-nius J. Anal. Chem., 359 (1997), 427D429. 

K. H. Schaller, J. Angerer, F. Alt, J. Messerschmidt, A. Weber, The determination of platinum in blood and urine as a tool for the biological monitoring of internal... 

M. Krachler, A. Alimonti, F. Petrucci, K. J. Irgoli , F. Forestiere, S. Caroli, Analytical problems in the determination of platinum-group metals in urine by quadrupole and magnetic sector E>eld inductively coupled plasma mass spectrometry, Anal. Chim. Acta, 363 (1998), ID 10. 

Gy. Zaray, M. vari, I. Salma, I. Steffan, M. Zeiner, S. Caroli, Determination of platinum in urine and airborne particulate matter from Budapest and Vienna, Micro-chem. J., 76 (2004), 31D34. 

H. Jones, Determination of platinum and palladium in blood and urine by Bameless atomic absorption spectrometry, Anal. Chem., 48 (1976), 1472D1474. 

S. M. Hopfer, L. Ziebka, F. W. Sunderman, J. R. Sporn, B. R. Greenberg, Direct analysis of platinum in plasma and urine by electrothermal atomic absorption spectrophotometry, Ann. Clin. Lab. Sci., 19 (1989), 389D396. 

B. Bocca, A. Alimonti, A. Cristaudo, E. Cristallini, F. Petrucci, S. Caroli, Monitoring of the exposure to platinum-group elements for two Italian population groups through urine analysis, Anal. Chim. Acta, 512 (2004), 19 D25. 

Electrochemical detection was easily employed for the determination of uric acid in urine, abnormal concentrations of which have been linked to several disease states [14]. A glass/PDMS hybrid device with an off-chip platinum electrode was used to evaluate standard samples for both dopamine and uric acid. The linear responses for dopamine and uric acid were 1-165 and 15-110 pM, respectively, with a 1 pM limit of detection for both. Normal concentrations of uric acid in urine are 800-8000 pM, thus a 50 to 75-fold dilution was used with the urine samples analyzed to place them within the linear range of the detection method. Uric acid concentrations in these urine samples were confirmed using the clinically accepted method. This new method should allow clinical detection of both abnormally high and abnormally low uric acid concentrations in urine samples on a microdevice. 

Kiss and coworkers78,79 synthesized some minor D-glucosiduronic acid metabolites of phenacetin (isolated from the urine of patients sensitive to phenacetin), namely, the conjugates of 2-acetamido-5-eth-oxyphenol and 5-acetamido-2-ethoxyphenol (33 and 35) by the platinum-catalyzed oxidation of the corresponding /3-D-glucopyranosides, and by the Koenigs-Knorr condensation of 1 with the appropriate ni-... 

The determination of the total platinum content in physiological fluids and tissues, both during clinical treatment or after environmental exposure, requires instrumental techniques of sufficient DLs and selectivities. ICP MS provides the most attractive DLs for platinum in biological samples, for example, 7.50 ng/L in human plasma ultrafiltrate after chemotherapy with cisplatin, carboplatin, and oxaliplatin [119] 0.1 pg/mL in blood, serum, and ultrafiltrate samples after chemotherapy with oxaliplatin and 5-fluorouracyl [120] 26 pg/g in DNA isolated from cancer ovarian cells after different exposure times and concentrations of cisplatin [121] and 0.75 pg in DNA extracts from peripheral blood mononuclear cells and tissues from patients treated with cisplatin [122] and 1.0 pg/L in serum, 0.1 pg/L in ultrafiltrate, and 2 pg/L in urine [123]. The ICP MS technique allowed detection of physiological levels of ft in the tmexposed human body 0.3-1.3 ng/L in blood (DL of 0.3 ng/L) [46] 0.48-7.7 ng/L in urine (DL of 0.24 ng/L) [47] and 0.778 ng/g... 

Oe, T., Tian, Y., O Dwyer, P.J., Roberts, D.W., Bailey, C.J., Blair, I.A. Determination of the platinum drug cii-amminedichloro(2-methylpyridine)platinum(Il) in human urine by liquid chromatography-tandem mass spectrometry. J. Chromatogr. B 792, 217-227 (2003)... 

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