Flameless Atomic Absorption Spectrometry Research Articles

Sodium ferrous citrate does not cause aluminum retention in rats with experimentally induced renal failure

Accumulation of aluminum (Al) in the brain and bone has been implicated in the development of encephalopathy and osteodystrophy in patients with renal failure, and it has been reported that citric acid enhances Al absorption and retention. Oral iron supplementation is usually carried out with recombinant human erythropoietin (rHuEPO) therapy in end-stage renal disease (ESRD) patients. Accordingly, there is a possibility that Ferromia (sodium ferrous citrate, tetrasodium biscitrato iron (II), E0708), which is used for the treatment of iron deficiency anemia, might accelerate Al absorption and retention. To investigate this possibility, we administered oral aluminum hydroxide [Al(OH)3] [50mg Al/kg body weight (BW)] with or without E0708 (48mg/kg BW or 480mg/kg BW) to 5/6-nephrectomized rats (n = 27) five times per week for 16 weeks, and determined the Al content of the serum, liver, cerebral cortex, and femoral bone by flameless atomic absorption spectroscopy. The low dose of E0708 corresponded approximately to the clinical dose, and its low and high doses contained 34.5mg/kg BW and 345.0mg/kg BW, respectively, of citric acid. In addition, we gave 5/6-nephrectomized rats Al(OH)3 with citric acid at 35mg/kg BW, which was identical to the citric acid dose of the low-dose regimen of E0708. The weight gain, serum urea nitrogen, and creatinine levels indicated that the rats developed mild to moderate renal failure. There was no significant increase of the Al content in the serum or organs of the Al(OH)3, + E0708-treated rats when compared with the Al(OH)3-treated rats and Al(OH)3 + citric acid-treated rats. These findings suggest that the usual clinical dose of E0708 does not promote Al retention in rats with mild to moderate renal failure or normal rats.

A Case of Massive Cisplatin Overdose Managed by Plasmapheresis

Objectives:Accidental cisplatin overdose occurs with increasing frequency despite the safeguards taken in prescription and administration, since cisplatin has been used increasingly for the treatment of numerous malignancies. Accidentally, a 59-year-old male received massive cisplatin overdose of 300mg/m2.Methods:Laboratory documentation included measurement of cisplatin concentrations by flameless atomic absorption spectroscopy(Varian, Spectra AA 300).Results:Toxicities included severe emesis, myelosuppression, renal failure, mental deterioration with hallucination, dim vision and hepatic toxicity. Plasmapheresis was effective in lowering the platinum concentration from greatest 2979 ng/ml to 185 ng/ml and appeared to be of clinical benefit.Granulocyte-macrophage colony stimulating factor(GM-CSF) was used to ameliorate myelosuppression. The patient's renal function was restored 3 months later and partial response of esophageal cancer was obtained.Conclusions:Plasmapheresis was effective in lowering the platinum concentration in massive cisplatin overdose. This case heightens awareness to the possibility of accidental cisplatin overdose and the benefits of prompt management.

Effects of storage on the binding of carboplatin to plasma proteins.

Plasma ultrafiltrates are routinely used in pharmacokinetic studies of carboplatin. Experiments were performed to detect and quantitate artifactual decreases in the platinum concentration of ultrafiltrates prepared from plasma samples stored at -20 degrees C and -70 degrees C. Carboplatin was added to anticoagulated, whole human blood to produce a 20 microgram/ml concentration. Plasma produced from the blood was stored frozen at either -20 degrees C or -70 degrees C. Aliquots from each storage condition were thawed and ultrafiltered once a week for up to 100 days. Platinum concentrations in ultrafiltrates and plasma were determined by flameless atomic absorption spectrometry. There was no loss of ultrafilterable platinum in plasma samples stored at -70 degrees C, whereas there was a steady decrease in free platinum concentration in ultrafiltrates prepared from plasma samples stored at -20 degrees C. These results imply that pharmacokinetic studies of carboplatin should use ultrafiltrates prepared immediately or that plasma for such studies should be stored at -70 degrees C. Storage of carboplatin-containing plasma at -20 degrees C and subsequent ultrafiltration is not acceptable, because measurement of platinum in such ultrafiltrates will be artifactually low.

Determination of lead and atmospheric particulates by flameless atomic absorption spectrometry

Flameless atomic absorption techniques were used to determine the lead and other atmospheric particulate in the city of Tehran. 640 samples were collected in 20 different stations around the city during four seasons in 1992. The radioactivity of the air samples was also measured by γ-ray spectrometry using high purity Ge/Li detectors, and a multichannel analyzer. The results were compared with previous measurements in the city of Tehran.

Pharmacokinetics and tissue distribution of cisplatin in nude mice: platinum levels and cisplatin-DNA adducts.

The pharmacokinetics of platinum (Pt) and cisplatin (CDDP)-DNA adducts were studied in nude mice after single-dose CDDP treatments. Whole blood, serum, kidney, lever, testis, brain, and tumor were collected at different intervals after injection of CDP at different dose levels. Pt was measured with flameless atomic absorption spectrometry (FAAS) or adsorptive voltammetry (AdV) and CDDP-DNA adducts with quantitative immunohistochemistry. The drug was immediately absorbed into the blood circulation (peak serum Pt levels were reached within 5 min) after i.p. CDDP administration, and distribution into most tissues also occurred rapidly (tissue Pt levels peaked at 15 min). With a sampling period of 7 days there was a biphasic elimination of Pt from blood, serum, and tissues. In the brain the pharmacokinetics differed with a gradual accumulation of Pt occurring during the 1st week. Formation of CDDP-DNA adducts in tissues was a slower process, with maximal levels being achieved at between 30 min and 4 h after drug administration, followed by a steady state lasting for at least 24 h. Each tissue type had its specific immunohistochemical staining pattern of adducts. With escalating CDDP doses there was a linear, or almost linear, increase in Pt concentrations and CDDP-DNA adduct levels in all sample types examined. These results suggest that a fair estimation of the amount of drug in tumor and normal tissues can be made from analysis of serum Pt at a fixed time point after a single dose of CDDP.

Titanium deposition in regional lymph nodes after insertion of titanium screw implants in maxillofacial region

The deposition of titanium in regional lymph nodes was studied after insertion of endosseous, plasma-spray-coated titanium screw implants in a total of 19 beagle dogs. Five additional animals with no implants served as the control group. After killing the animals 9 months postoperatively, the regional lymph nodes were carefully excised, and samples were prepared for histologic examination. Other samples were used to identify foreign particles by energy-dispersive x-ray analysis and for measurement of the titanium concentration in the tissue by flameless atomic absorption spectroscopy. Very fine foreign-body particles could be seen in the histologic sections, and they were identified as titanium by energy-dispersive x-ray analysis. The atomic absorption analysis for titanium revealed a significantly higher concentration in the group with implants. The presence of very fine, poorly attached particles on the plasma-sprayed titanium surface suggests that these particles may be mechanically dislodged from the surface on insertion of the implants. This suggests that the fine particles may be transported by phagocytes to the regional lymph nodes, where they could be found without any signs of inflammation or foreign-body reaction.

Analysis of enloplatin by liquid chromatography and of platinum by atomic absorption spectrometry in various biological fluids

Analytical methods were developed and validated for the determination of enloplatin (an anticancer agent) in plasma by reversed-phase LC and for platinum (an elemental component of enloplatin) in plasma, plasma ultrafiltrate (PUF) and whole blood by flameless atomic absorption spectrometry (FAAS). The LC procedure involved protein precipitation with dilute perchloric acid. The supernatant was mixed with sodium phosphate buffer and injected into the LC system. A C18 or a cyano column was used, depending on sample matrix, with UV detection at 230 nm. The LC method was linear from 0.50 to 50.0 micrograms ml-1. Inter-day and intra-day precision (RSD%) and accuracy (relative error%) were < +/- 14%. The FAAS procedure utilized a graphite furnace, a hollow cathode platinum (Pt) lamp, and Zeeman background correction. An aliquot of plasma, PUF, or whole blood was mixed with a solution of Triton X-100 and Antifoam-B and injected into the FAAS system. The FAAS method showed goodness of fit from 0.05 to 10.0 micrograms Pt/ml. Inter-day and intra-day precision and accuracy were < +/- 15%. The methods were developed to support pharmacokinetic studies in humans, dogs and rats.

A comparison between endogenous and exogenous lithium clearance in the anaesthetized rat

The present study tests whether the endogenous renal lithium clearance (CLi) may be used as an alternative to the conventional method in order to avoid the adverse effects of exogenous lithium on renal function. Endogenous CLi) was measured by flameless atomic absorption spectrometry (AAS) in halothane anaesthetized, laparotomized rats and compared with values obtained after subsequent intravenous (i.v.) administration of LiCl. Endogenous plasma lithium concentration (PLi) was 0.30 +/- 0.06 mumol l-1. When measured by both conventional flame emission AAS and flameless AAS on the same samples, values for PLi did not differ significantly. Endogenous CL1/GFR was 0.195 +/- 0.01 (mean +/- SEM). Amiloride caused on significant change in either the endogenous CLi or 51Cr-EDTA clearance, a measure of glomerular filtration rate (GFR), but it caused a significant increase in CNa. Administration of exogenous Li+ had no significant effect on CLi (230 +/- 33 vs. 234 +/- 35 microliters min-1 gKW-1); both urine flow and CNa increased significantly (P < 0.01) (5.4 +/- 0.4 vs. 9.6 +/- 1.3, and 2.4 +/- 0.5 vs. 10.7 +/- 2.4 microliters min-1 gKW-1, respectively). GFR and calculated proximal tubular reabsorption rate (APR) both decreased by approximately 100 microliters min-1 gKW-1 (both P < or = 0.025), suggesting a moderate inhibition of APR after the acute elevation of plasma Li+ concentration. It is concluded that the endogenous CLi may be used as an alternative to the conventional method.

Elemental status of grazing animals located adjacent to the London Orbital (M25) motorway

The elemental (Br, Cd, Cr, Cu, Mn, Ni, Pb, Se, V, and Zn) content of blood and wool or hair from animals (sheep, horses and alpacas) exposed to motor vehicle emissions alongside the London Orbital (M25) motorway is reported. Elemental values were determined by inductively coupled plasma mass spectrometry (ICP-MS) quality control assessment using flameless atomic absorption spectroscopy (for Pb, correlation coefficients of whole blood r = +0.87, and hair r = +0.82), and replicate ( n = 10) analysis of the international reference material IAEA A13 Animal Blood. For Pb very good agreement was obtained between ICP-MS values 0.16 ± 0.002 μg/g and non-certified values 0.18 μg/g. Only Pb and Cd showed significantly elevated blood levels in sheep grazing alongside the M25 motorway when compared with control (background) animals. The range of Pb blood values was 0.15–0.51 μg/ml (M25) and 0.04–0.18 μg/ml (control), respectively. The elemental content of the outside (tip) end of wool samples for the two study groups were significantly elevated in Br, Cd, Cr, Cu, Ni, Pb, V, and Zn for M25-exposed animals compared with controls. Elevated Pb and Cd were also found in horses' and alpacas' blood or hair in animals exposed to transportational activities. The relationship between whole blood and outer wool or hair Pb showed a very highly significant correlation for sheep ( r = +0.89), horses ( r = +0.69), and alpacas ( r = +0.74) grazing alongside the M25 motorway.

Elemental analysis of small glass fragments in forensic science

The evidential value of small glass particles has been recognized for quite some time. While physical properties such as refractive index and density offer some discrimination of glass samples, they offer little in the way of classification of glass product type. Further, with improved glass manufacturing processes, the range of physical properties seen in modern glass samples is continually decreasing. Many have advocated the use of elemental analysis for the purposes of forensic glass analaysis. Various instrumental techniques have been employed to this end, including flameless atomic absorption spectrometry, inductively coupled plasma atomic emission spectrometry, and energy dispersive X-ray fluorescence spectrometry. These more commonly employed methods are discussed with regard to the application to forensic glass analysis. Advantages and disadvantages of each technique are highlighted.

Enhanced repair of a cisplatin-damaged reporter chloramphenicol-O-acetyltransferase gene and altered activities of DNA polymerases alpha and beta, and DNA ligase in cells of a human malignant glioma following in vivo cisplatin therapy.

Current evidence suggest an important role for increased repair of drug-induced DNA damage as one of the major mechanisms involved in tumor cell resistance to cis-DDP. In this study, we examined the DNA repair capacity and the activities of three DNA repair related proteins, namely, DNA polymerases alpha and beta, and total DNA ligase in cells of a malignant oligodendroglioma obtained from a patient before therapy and compared it with those of a specimen of the tumor acquired after the patient had failed cis-DDP therapy. DNA repair capacity was quantitated as the extent of reactivation of the chloramphenicol-O-acetyltransferase (CAT) gene in a eukaryotic expression vector that had been damaged and inactivated by prior treatment with cis-DDP and then transfected into the tumor cells. The extent of DNA-platinum adduct formation in the expression vector was determined by flameless atomic absorption spectrometry. The level of cis-DDP resistance of cells of the two tumors was determined with the capillary tumor stem cell assay. We observed a 2.8-fold increased capacity to repair Pt-DNA adducts and reactivate the CAT gene in cells of the tumor obtained after cis-DDP therapy, compared to cells of the untreated tumor. This was associated with increases of 9.4-fold and a 2.3-fold, respectively, in DNA polymerase beta and total DNA ligase activities in cells of the treated tumor. At 5 microM cis-DDP, there was a 5.9-fold increase in the in vitro cis-DDP resistance of post-therapy tumor cells relative to cells of the untreated tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Trace element (Cu, Zn, Fe, Mn, Se) intakes of a group of French men using the duplicate diet technique

In France there is little information on trace element intakes. The present work reports the average daily trace element intakes from French collectivity diets (Grenoble Hospital). Fourteen healthy adult men were enrolled in this trial. Foods and beverages consumed were collected daily for 5 consecutive days, using the duplicate diet technique. Zn, Cu, Mn, and Fe were determined in lyophilised daily samples by flameless atomic absorption spectrometry, whereas Se was determined by gas chromatography-mass spectrometry. The average daily intakes were found to be 1.2 ± 0.05 mg for Cu, 10.8 ± 0.39 mg for Fe, 3.7 ± 0.15 mg for Mn, 10.5 ± 0.47 mg for Zn and 48 ± 3 μg for Se. The micronutrient densities were 0.12 ± 0.005 mg/MJ (0.52 ± 0.021 mg/1000kcal) for Cu, 1.12 ± 0.045 mg/MJ (4.7 ± 0.19 mg/1000kcal) for Fe, 0.39 ± 0.017 mg/MJ (1.64 ± 0.069 mg/1000kcal) for Mn, 1.10 ± 0.049 mg/MJ (4.6 ± 0.20 mg/1000 kcal) for Zn and 5.11 ± 0.362 μg/MJ (21.4 ± 1.51 μg/1000kcal) for Se. Expressed per kg body weight, daily intak...

Mercury concentrations in benthic animals and plants inhabiting the Gulf of Gdańsk, Baltic Sea

Mercury concerntrations were investigated on field collections of benthic animals (Gammarus sp., Macoma baltica, Mytilus edulis, Balanus improvisosus, Crangon crangon and Mesideothea entomon) and plants (Enteromorpha sp., Zostera marina, Pyloiella litoralis, Potamogeton pectinatus, Ruppia maritima, Cladophora rupestris, Ulva lactica and Elodea canadensis) taken in the western part of the Gulf of Gdansk and the adjacent waters in 1988–1989. The method of measurement was cold vapour flameless atomic absorption spectrometry. Some inter-species and spatial differences in mercury concentrations of zoobenthos could be observed, indicating both pollution from local land based nonpoint sources and higher accumulation in sedimentation areas. However, the mercury concentrations noted were relatively low and within the lowest values observed by other authors for the same species in other than the Gulf of Gdansk regions of the Baltic Sea.

Noninvasive follow-up of platinum pharmacokinetics in the skin of patients on cisplatin chemotherapy

Treatment with high-dose cisdiammine-dichloroplatinum (II) (cisplatin, cDDP) often is associated with late complications, predominated by peripheral neuropathy. Pt deposition in different tissues may play a key role in the induction of many of these effects. Main topics of interest include the relationship between cDDP doses given during treatment and the long-term pharmacokinetics of the drug complexes in normal tissues and blood. Noninvasive examination of Pt in tissues during and after cDDP treatment are needed to clarify these points. A novel, high-sensitivity diagnostic x-ray spectrometry (DXS) method was used for the fast, noninvasive analysis of Pt in external tissues of patients with cancer treated with courses of cDDP. The Pt in a small skin area was excited by a monochromatic soft x-ray beam (14.6 KeV) and the spectral L lines emitted from the tissue were detected. A limit of detection below 1 microgram/g wet weight was reached. The pharmacokinetics of Pt in blood was investigated in parallel with the use of high-sensitivity, flameless atomic absorption spectrometry (AAS). Follow-up of Pt concentrations in the skin of patients with cancer by DXS before cDDP treatment, during treatment, and up to 4 months after its completion, showed prolonged Pt deposition that corresponded to the net cumulative doses of the drug. Pt clearance from the skin fitted a monoexponential curve with a half-life of about 30 days. In comparison, the pharmacokinetics of total Pt in plasma showed a much faster, biexponential clearance with half-lives of 41 minutes and 5.2 days, respectively. The amount of nonspecific Pt deposition in the tissues was found to depend on the total doses administered, the time interval between the courses, and the slow rate of clearance. Noninvasive measurements of tissue Pt levels may serve as a major tool in the evaluation of the induction of late cDDP complications.

In situ lung perfusion with cisplatin an experimental study

This research work was planned to evaluate the soundness of in situ lung perfusion as a regional administration modality of chemotherapeutic agents. Sixteen pigs were randomly divided into four groups and received cisplatin (2.5 mg/kg) through the pulmonary artery using one of the following techniques: stop-flow (Group 1); stop-flow/out-flow occlusion (Group 2); lung perfusion (Group 3); or lung perfusion with 5 mg/kg of infused drug (Group 4). Serial blood (carotid, pulmonary artery and vein) and tissue samples (lung and mediastinal node), were taken before, at completion of, and 5, 10, 15, 30, 60, 120, 180 and 240 minutes after cisplatin infusion for blood gas and platinum content measurement. Blood circulation was restored to the treated organ (for 60 minutes). The animals were killed, and specimens from lung, thyroid, esophagus, heart, liver, spleen, adrenal glands, kidney, bone marrow, stomach, ileum, colon, psoas muscle, and skin were obtained. Platinum concentrations in plasma, plasma ultrafiltrate (free platinum) urine, and tissues were determined by flameless atomic absorption spectroscopy. Lung damage was evaluated by light and electron microscopic examination. Greater systemic plasma, lower pulmonary plasma, and tissue platinum levels were detected when cisplatin was given using the stop-flow technique with respect to the other administration modalities. No significant difference in regional and systemic platinum exposure was found between Groups 2 and 3. However, lung perfusion resulted in higher mediastinal node and lower bone marrow platinum values. Morphologic alterations and impairment of gas exchanges in the treated lung were not dependent on the applied infusion technique. This study provides the pharmacokinetic rationale for the application of lung perfusion to patients with pulmonary metastases.

Copper-Metallothionein Distribution in the Liver of Long-Evans Cinnamon Rats: Studies on Immunohistochemical Staining, Metal Determination, Gel Filtration and Electron Spin Resonance Spectroscopy

Distribution of methallothionein (MT) and copper ion (Cu) in the liver of LEC (Long-Evans Cinnamon) rats was investigated to examine the relationship between Cu-MT induction and the development of hepatitis followed by hepatocellular carcinomas. Immunohistochemical studies on MT in the liver of LEC rats indicated that MT is accumulated in nuclei and cytosols. Both MT and Cu, estimated by radioimmunoassy and flameless atomic absorption spectrometry, respectively, in subcellular fractions of the liver were found to be concentrated highest in cytosols, followed by nuclei, mitochondria and microsomal fractions. Gel-filtration (Sephadex G-75) studies demonstrated that MT is induced as the Cu-MT form. Furthermore, the Cu-MT fragment purified by the gel-filtration contains the Cu(I)-MT form, as demonstrated by ESR (electron spin resonance) measurements at 77K. These results will be important for understanding the development of hepatitis in LEC rats.

Spuriously Low Concentrations of Serum Iron Measured with Generation 14 Kodak Ektachem Slides: Prevalence, Possible Causes, and Partial Improvement with Generation 16 Slides

For sera with iron (Fe) concentrations < 4 mumol/L, Kodak Ektachem slides Generation (GEN) 14 (without ascorbic acid) yielded systematically lower results for Fe than did liquid Ferrozine-based reagents from Baker containing ascorbic acid (10 g/L, final concentration) and adapted to Cobas-Bio. During an 8-month comparison period, outliers (defined as [Fe]Cobas - [Fe]Kodak > 4 mumol/L) were seen in 21 of the 8731 sera (0.24%) tested, corresponding to < 5% of the sera with [Fe]Kodak < 4 mumol/L. In vitro addition of ascorbic acid and (or) Fe identified at least two types of outliers: type 1 (approximately 70%), characterized by [Fe]Kodak > 0.4 mumol/L, by (supra)normal Fe recovery in Kodak slides in the presence or absence of ascorbic acid (10 g/L), and by between-method differences in serum Fe (Cobas - Kodak) that were significantly correlated with serum Zn content (P < 0.0004); and type 2 (approximately 30%), tentatively ascribed to contamination by EDTA, with serum Fe by Kodak < 0.4 mumol/L and Fe recovery near 0%, both of which could be significantly and dose-dependently increased by addition of ascorbic acid (5-20 g/L). For both types of outliers, flameless atomic absorption spectrometry (AAS) yielded results that were significantly higher than concentrations by Kodak with GEN 14. Use of GEN 16 slides (containing ascorbic acid) improved concordance of Kodak results with Cobas, and hence with flameless AAS, for both types of outliers; abolished Zn dependency of results; and increased Fe results in sera with type 2 outliers, although these remained substantially lower than by Cobas. However, like other ascorbic acid-containing reagents, GEN 16 slides were more sensitive to interference by dextran-bound Fe, as assessed during in vitro addition experiments and comparisons involving samples from Fe-dextran-treated patients. GEN 16 slides are hence expected to more frequently overestimate the physiologically available protein-bound Fe in hemodialysis patients. In hospital laboratories, this new interference will probably arise more frequently than the spuriously low results with GEN 14, hence warranting further efforts in optimizing Fe slides.

Preconcentration of Trace Metal Ions by Coprecipitation with Gallium Phosphate for Flameless Atomic Absorption Spectrometry

Abstract Gallium phosphate was a useful coprecipitant for the preconcentration of lead(II), tin(IV), antimony(III), and bismuth(III) on the flameless atomic absorption spectrometry. The determination of trace amount of lead(II) in water was demonstrated.

Micro method for determination of cadmium in tissues and slurried samples by use of flameless atomic absorption spectrometry

Cadmium (Cd) was determined in rat liver, kidneys, brain, testes, heart, and lungs with graphite furnace atomic absorption spectrometry following digestion of micro quantities (100 μl) of tissue homogenates in polypropylene micro diagnostic tubes. Microwave heating was used to complete the digestion. Results obtained demonstrated adequate precision, as indicated by relative standard deviations in control (±14%) and treated rat tissues (±2.6%). Cd measured in Standard Reference Materials that represented various biological tissues agreed with certified values, and no significant differences were observed between results obtained by use of the method of additions and those obtained by use of matrix-free reference solutions. Overall mean recovery of Cd added to Cd-treated rat tissue homogenates prior to the digestion procedure was 96%.

Zinc Concentrations in Human Tissues: Liver Zinc in Carcinoma and Severe Liver Disease

In 58 unselected necropsies, zinc (Zn) in specimens of liver (mean +/- s = 280 +/- 178 micrograms/g d.w./4.28 +/- 2.72 mumol/g d.w.), kidney (170 +/- 57 micrograms/g d.w./2.60 +/- 0.87 mumol/g d.w.), spleen (69 +/- 13 micrograms/g d.w./1.05 +/- 0.20 mumol/g d.w.), and lung (64 +/- 16 micrograms/g d.w./0.98 +/- 0.24 mumol/g d.w.) were analysed by means of flameless atomic absorption spectrometry. In the examined range from 25 to 92 years of age, the Zn concentrations in all tissues measured did not show age or sex-dependency. There was a high correlation between the tissue concentration of Zn and Mg in lung, liver, and spleen, between Zn, Mg, and Pb in liver as well as between Zn and Pb and Zn and Cd in kidney. All hepatic cirrhosis cases had very low Zn conc. in liver tissue, the tumor cases generally increasing Zn conc. in liver tissue with progressive stage of regional invasion and distant metastasis.