Determination of uranium in urine – measurement of isotope ratios and quantification by use of inductively coupled plasma mass spectrometry

For analysis of uranium in urine determination of the isotope ratio and quantification were investigated by high-resolution inductively coupled plasma mass spectrometry (HR ICP-MS). The instrument used (ThermoFinniganMAT ELEMENT2) is a single-collector MS and, therefore, a stable sample-introduction system was chosen. The methodical set-up was optimized to achieve the best precision for both the isotope ratio and the total uranium concentration in the urine matrix.Three spiked urine samples from an European interlaboratory comparison were analyzed to determine the (235)U/(238)U isotope ratio. The ratio was found to be in the range 0.002116 to 0.007222, the latter being the natural uranium isotope ratio. The first ratio indicates the abundance of depleted uranium.The effect of storage conditions and the stability for the matrix urine were investigated by using "real-life" urine samples from unexposed persons in the Netherlands. For samples stored under refrigeration and acidified the results (range 0.8 to 5.3 ng L(-1) U) were in the normal fluctuation range whereas a decrease in uranium concentration was observed for samples stored at room temperature without acidification.     

Multielement determinations in ground water ultrafiltrates using inductively coupled plasma mass spectrometry and monostandard neutron activation analysis

Twelve ultrafiltrates of two ground waters rich in humic substances (up to 97.8 mg CL^–1) and in salinity (up to: cations 44.3 meq L^–1, anions 44.9 meq L^–1) were investigated with ICP-MS and with NAA in parallel. With both techniques 22 elements were analysed in a wide concentration range (mg/L to ng/L). Ultrafiltration at pore sizes from 1000 nm down to 1 nm lowers the humic colloid content as well as the concentration of the colloidborne polyvalent cations. Carbon interferences were studied in detail using artificially prepared model waters. The detection limits of ICP-MS in the ultrafiltrates (0.01 g/L–10 g/L) and in pure analyte solutions (5 ng/L–600 ng/L) are compared with those of NAA for pure water analysis (0.004 ng/L–50 ng/L).Dedicated to Professor Dr. H. Schmidbaur on the occasion of his 60th birthday     

Sensitive biomonitoring of phthalate metabolites in human urine using packed capillary column switching liquid chromatography coupled to electrospray ionization ion-trap mass spectrometry

A rapid and sensitive method for the determination of the phthalate monoesters monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP) and monoethylhexyl phthalate (MEHP), in human urine, using packed capillary column liquid chromatography coupled to electrospray quadrupole-ion trap mass spectrometry (ESI-QITMSⁿ) has been developed. Sample volumes of 200 L of deconjugated and diluted urine were loaded onto a precolumn of 30 mm×0.32 mm I.D. packed with Hypercarb 5 m particles, using a sample carrier consisting of acetonitrile/water (15/85, v/v, adjusted to pH 2 using HCl) with a flow rate of 20 L/min. Backflushed elution onto a 100 mm×0.32 mm I.D. analytical column packed with 5 m Hypercarb particles was conducted using a tetrahydrofuran/water gradient where both solvents contained 10 mM ammonium acetate, at a flow rate of 4 L/min. Determination of the monophthalates was achieved within 8 min. Ionization was performed in the negative mode and the analytes were observed as [M-H]^– at m/z=193.1, 221.1, 255.1 and 277.0 for MEP, MBP, MBzP and MEHP, respectively. Quantification was performed in the multiple reaction monitoring (MRM) mode monitoring the fragments at m/z=121.1, 177.0, 183.0 and 233.0 for MEP, MBP, MBzP and MEHP, respectively. The method was validated over the concentration range 2.5–125 ng/mL in pretreated urine samples, corresponding to 25–1250 ng/mL untreated urine, yielding correlation coefficients in the range 0.996–0.999. The within-assay (n=6) and between-assay (n=6) repeatabilities were in the range 4.0–18% and 4.8–15% RSD, respectively. The mass limits of detection were in the range 32–70 pg, corresponding to concentration limits of detection of 1.6–3.5 ng/mL of untreated urine.     

Use of chromatographic pre-concentration for routine uranium bioassay analysis by ICP-MS

Routine monitoring of urine is an effective way to detect occupational intake of radioactive material. Historically, determinations of uranium isotopic ratios have been performed by radiochemical separation followed by alpha spectrometry. With recent advancements in technology, inductively coupled plasma-mass spectrometry (ICP-MS) has become widely available for the determination of trace metals as well as radioactive nuclides with long half-lives, such as ²³⁸U in urine. Furthermore, ICP-MS measurements of ²³⁸U do not require radiochemical separation since the number of atoms in the sample is determined instead of the number of alpha particles emitted. However, this method does not provide good sensitivity for the determination of ²³⁵U due to its shorter half-life. An improved procedure using pre-concentration of uranium and determination by ICP-MS decreases the detection limit by a factor of ten or greater with only slight increase in total analysis time. The method also has the capability of accurately determining the isotopic ratio of the sample, which is very important in cases where enriched or depleted uranium is involved.     

Ultratrace analysis of uranium and thorium in glass

Three methods of determination for uranium and thorium traces and ultratraces in glass were developed: a simple and powerful ICP-MS method exhibiting limits of determination in the one ng/g-range; a complex method with end-determination by classical photometry and a limit of determination for U and Th of 20 ng/g; and a method with chelate-complex formation for U and Th and subsequent GC-detection with a ⁶³Ni-ECD with limits of determination in the g/g-range. These methods are critically compared and tested for real type samples of special glasses.Abbreviations used AAS Atomic absorption spectrophotometry - ECD Electron capture detector - FOD 1,1,1,2,2,3,3-Heptafluoro-7,7-dimethyl-4,6-octanedion - GC Gas chromatography - HFA 1,1,1,5,5,5-Hexafluoro-2,4-pentanedione - ICP-AES, -MS Inductively coupled plasma-atomic emission spectrometry, metry, -mass spectrometry - LAS Liquid absorption spectrophotometry = classical photometry - NAA Neutron activation analysis - NIST National Institute of Standardization and Technology (Gaithersburg, U.S.A.) - TBP Tri-(n-butyl)-phosphate - TFA 1,1,1-Trifluoro-2,4-pentanedione - TTFA 1-(2-Thenoyl)-3,3,3-trifluoroacetone - XRS X-ray (fluorescence) spectrometry     

Determination of Mercury in Urine and Seawater by Flow Injection Vapor Generation Isotope Dilution Inductively Coupled Plasma Mass Spectrometry

A simple and inexpensive laboratory-built vapor generator was used with inductively coupled plasma mass spectrometry (ICP-MS) for the determination of mercury in urine and seawater samples. The applications of vapor generation ICP-MS alleviated the non-spectroscopic interferences and the sensitivity problem of mercury determination encountered when the conventional pneumatic nebulizer was used for sample introduction. The concentration of mercury was determined by isotope dilution method. The isotope ratio of mercury was calculated from the peak areas of each injection peak. The repeatability of the peak areas and isotope ratio determinations of seven consecutive injections of 1 ng mL^?1 Hg solution were 2.3% and 2.2%, respectively. This method has a detection limit of 0.07 ng mL^?1 for mercury. This method was applied to determine mercury in a CASS-3 nearshore seawater reference sample, NASS-4 open ocean seawater reference sample, NIST SRM 2670 freeze-dried urine reference sample and several urine and seawater samples collected from National Sun Yat-Sen University. The results for the reference samples agreed satisfactorily with the reference values. Results for other samples analyzed by the isotope dilution method and the method of standard additions agreed satisfactorily. Precision was better than 10% for most of the determinations.     

Determination of total urinary mercury by on-line sample microwave digestion followed by flow injection cold vapour inductively coupled plasma mass spectrometry or atomic absorption spectrometry

The total mercury content in urine was determined by inductively coupled plasma mass spectrometry with the so-called cold vapour method after on-line oxidative treatment of the sample in a microwave oven (FI-MW-CV-ICPMS). Use of a KBr/KBrO(3) mixture, microwave digestion, and the final oxidation with KMnO(4), assure the complete recovery of the organic forms of Hg which would be difficult to determine otherwise if using only the CV-ICPMS apparatus. Quantitative recoveries were obtained for phenyl Hg chloride (PMC), dimethyl Hg (DMM), Hg acetate (MA) and methyl Hg chloride (MMC). Use of automatic flow injection microwave systems (FI-MW) for sample treatment reduces environmental contamination and allows detection limits suitable for the determination of reference values. Since no certified reference materials were commercially available in the concentration ranges of interest, the accuracy of the proposed procedure has been assessed by analysing a series of urine samples with two independent techniques, ICP-MS and AAS. When using the FI-MW-CV-ICP-MS technique, the detection limit was assessed at 0.03microg/L Hg, while with FI-MW-CV-AAS it was 0.2microg/L Hg. The precision of the method was less than 2-3% for FI-MW-CV-ICP-MS and about 3-5% for FI-MV-CV-AAS at concentrations below 1microg/L Hg. These results show that ICP-MS can be considered as a "reference technique" for the determination of total urinary Hg at very low concentrations, such as are present in non-exposed subjects.     

Direct determination of antibacterial norfloxacin in urine by isopotential fluorimetry

A novel and simple method is presented for the determination of norfloxacin in human urine by matrix isopotential synchronous fluorescence spectrometry (MISF). This method is useful for the determination of compounds in samples with unknown background fluorescence, such as norfloxacin in urine, without the need for tedious sample pre-treatment. The method was performed in ethanol-water medium (10% v/v), at an apparent pH of 4.8 provided by adding sodium acetate-acetic acid buffer solution. In the determination of norfloxacin in urine the fluorescent intensity varied linearly with its concentration from 20 to 200 ng/mL. An exhaustive statistical analysis has been developed to all calibration graphs, this treatment includes robust regression such as least median of squares, which also detects outliers and leverage points. The overall least-squares regression has been applied to find the more exact straight line that fits the experimental data. The error propagation has been considered to calculate the detection limit and the repeatability of the method. The method shows very low detection limits with acceptable recoveries and precisions. The applicability of the proposed method was illustrated in the determination of norfloxacin in human urine sample without sample pre-treatment.     

A rapid in vitro assay of cobalamin in human urine and medical tablets using ICP-MS

A rapid and simple as well as sensitive inductively coupled plasma mass spectrometry (ICP-MS) method for the determination of cobalamin is described. Cobalamin in human urine and medicine tablet solutions was converted on-line into free cobalt ions in acid medium, the cobalt ions were then detected by ICP-MS. Cobalamin was determined by measuring the increase of integral counts per second intensity, which was linear over the cobalamin concentration range of 1.0 × 10⁻¹⁰ g mL⁻¹ to 8.0 × 10⁻⁵ g mL⁻¹, and the limit of detection was 0.05 ng mL⁻¹ (3σ). At the pump rate of 30 rotations per minute, one analysis cycle of cobalamin, including sampling and washing, could be accomplished in 0.5 min with the relative standard deviations of less than 5 %. The proposed procedure was applied successfully in monitoring cobalamin in human urine without any pretreatment process and in rapid determination of cobalamin in multivitamin tablets.     

Determination of rare earth elements in urine by electrothermal vaporization inductively coupled plasma mass spectrometry

A method was developed for the determination of rare earth elements (REEs) in urine with electrothermal vaporization inductively coupled plasma mass spectrometry (ETV-ICPMS). The undiluted sample was directly injected into the graphite tube and trifluoromethane (Freon-23) was used as chemical modifier in order to reduce the vaporization temperature and the memory effect of most of the lanthanides. The detection limits were in the range 1-10 ng/L with relative standard deviation of 3-5% at concentration levels of 1microg/L, and less than 10-15% at 100 ng/L. Two different procedures, external calibration and a standard additions method, were evaluated to measure the concentration levels of lanthanides in the urine samples and the second procedure was considered to be the best choice for calibration in this work. The level of REEs in urine of 50 healthy volunteers was in the range 5-20 ng/L, above the detection limit of ETV-ICPMS.     

Capability of ICP-MS (pneumatic nebulization and ETV) for Pt-analysis in different matrices at ecologically relevant concentrations

ICP-MS both with conventional nebulization and with ETV (Electro Thermal Vaporization) have been applied for the determination of Pt in different matrices, e.g. occupational samples like urine and dust samples. It can be used also for other matrices like soil, plants, tissues etc. dependent on the concentration ranges and on a suitable decomposition method. The evaluation, based on the different Pt-isotopes and the quality criteria (detection limit, precision, accuracy) is discussed. Very low determination limits in the range of 1 ng/l can be achieved by ICP-MS-ETV using the standard addition method. This method allows to determine Pt in urine without any sample pretreatment.     

Capability of ICP-MS (pneumatic nebulization and ETV) for Pt-analysis in different matrices at ecologically relevant concentrations

ICP-MS both with conventional nebulization and with ETV (Electro Thermal Vaporization) have been applied for the determination of Pt in different matrices, e.g. occupational samples like urine and dust samples. It can be used also for other matrices like soil, plants, tissues etc. dependent on the concentration ranges and on a suitable decomposition method. The evaluation, based on the different Pt-isotopes and the quality criteria (detection limit, precision, accuracy) is discussed. Very low determination limits in the range of 1 ng/l can be achieved by ICP-MS-ETV using the standard addition method. This method allows to determine Pt in urine without any sample pretreatment.Dedicated to Professor Dr. Peter Brätter on the occasion of his 60th birthday     

Determination of dextromethorphan and dextrorphan in urine by capillary zone electrophoresis: Application to the determination of debrisoquin-oxidation metabolic phenotype

Summary A capillary zone electrophoresis method has been developed for the determination of dextromethorphan and its metabolite, dextrorphan, in urine. A linear relationship was observed between the peak area and the concentration of both dextromethorphan and dextrorphan within the range of 490 ng mL^–1 to 500 g mL^–1 with a correlation coefficient of greater than 0.9999. The limit of detection was 80 ng mL^–1 for both compounds. The inter-day coefficients of variation for the concentrations of 2.5 g mL^–1 and 50 g mL^–1 were 6.2% and 4.1% for dextromethorphan, and 5.6% and 2.8% for dextrorphan (n=15). The method could be applied directly to the determination of dextromethorphan and dextrorphan in human urine without any sample pretreatment for the elimination of interfering compounds as is required in published highperformance liquid chromatography and gas chromatography methods. Using dextromethorphan as a probe of the debrisoquin-oxidation metabolic phenotype, the 44 healthy volunteers were phenotyped after oral administration of a 15 mg dose using both this capillary electrophoresis method and a high-performance liquid chromatography assay from the literature. Good agreement was found between the two methods.     

Polyurethane foam chips combined with liquid chromatography in the determination of unmetabolized polycyclic aromatic hydrocarbons excreted in human urine

A method suitable for the determination of unmetabolized polycyclic aromatic hydrocarbons (PAHs) excreted at trace levels (ng/L) in human urine for the monitoring of exposure of the general population to PAH contamination was developed. PAHs were determined, after enrichment by solid-phase extraction on polyurethane foam (PUF) chips, by HPLC with fluorescence detection. Different parameters affecting analyte extraction to the PUF, including urine salting-out and organic additives, and optimization of conditions for clean-up and desorption have been investigated. Optimized conditions were 40 mL acidified urine sample, added with magnesium sulfate, tetrahydrofuran and a 2 cm3 PUF chip, and extracted by shaking at 30 rpm for 1 h at ambient temperature. Desorption was performed, after a clean-up step with diluted sodium hydroxide, using a small amount of diethyl ether. The recovery of PAH congeners from spiked urines was >90% in the 2-100 ng/L range; the detection limit was 0.1-0.5 ng/L, depending on the considered PAH congener; day-to-day precision, at 50 ng/L native PAH content, was CV = 10-20%. The proposed technique provides a simple, economical and effective procedure for the determination of trace amounts of unmetabolized PAHs excreted in human urine spot samples.     

Simultaneous chiral separation and determination of carvedilol and 5′-hydroxyphenyl carvedilol enantiomers from human urine by high performance liquid chromatography coupled with fluorescent detection

A sensitive and specific high performance liquid chromatography coupled with fluorescent detection (HPLC-FL) and tandem mass spectrometry detection (HPLC-MS/MS) methods for separation and determination of carvedilol (CAR) enantiomers and 5′-hydroxyphenyl carvedilol (5′-HCAR) enantiomers has been developed and validated. The analysed compounds were extracted from human urine by solid phase extraction. Good enantioseparation of the studied enantiomers was achieved on CHIRALCEL® OD-RH column using 0.05% trifluoroacetic acid and 0.05% diethylamine in water and acetonitrile in a gradient elution. The mass spectrometric data were acquired using the multiple reaction monitoring mode by positive electrospray ionisation. The method was validated over the concentration range from 25.0 ng mL^?1 to 200 ng mL^?1 for the analysed compounds. The limit of quantification varied from 14.2 ng mL^?1 to 24.2 ng mL^?1. Both the repeatability and inter-day precisions were below 10.0%, and the accuracy varied from ?13.2% to 3.77%. The extraction recoveries ranged from 79.2% to 108%. The present paper reports the method for the simultaneous determination of CAR enantiomers and their metabolite enantiomers (5′-HCAR) in human urine samples. This newly developed method was successfully used to analyse the aforementioned analytes in human urine samples obtained from patients suffering from cardiovascular disease.      

Development of new centrifuges for fast solvent extraction of transactinide elements

Inductively coupled plasma-mass spectrometry (ICP-MS) was used to concurrently determine multiple long-lived (t_1/2>10⁴ y) actinide isotopes in soil leachates. Ultrasonic nebulization was found to maximize instrument sensitivity. Instrument detection limits for actinides in solution ranged from 50 mBq L^–1 (²³⁹Pu) to 2Bq L^–1 (²³⁵U). Hydride adducts of²³²Th and²³⁸U interfered with the determinations of²³³U and²³⁹Pu; thus, extraction chromatography was used to concentrate the analytes and separate uranium from the other actinides in advance of mass spectrometric determination. Alpha spectrometric determinations of²³⁰Th,²³⁹Pu, and the²³⁴U/²³⁸U activity ratio in soil leachates compared well with ICP-MS determinations; however, there were some small systematic differences (ca. 10%) between ICP-MS and -spectrometric determinations of²³⁴U and²³⁸U activities. These differences were attributed to the use of different isotope dilution spikes for ICP-MS and -spectrometry.     

Determination of trace metals in hydrothermal calcites by ICP-methods

Lanthanum, cerium, and europium in calcites from carbonate-sulfide banded ores were determined by standard addition using inductively coupled plasma mass spectrometry (ICP-MS). The concentration ranges in solution were for La 700-36 ng/g, Ce 2000-149 ng/g, and for Eu 140-2.4 ng/g. Only Ce was determined by both ICP methods, and the results agree within 3 to 4%. In a second step, a scan over the mass range of the rare earth elements (REE) was performed. The solutions were analyzed directly without applying preconcentration or separation procedures. ICP atomic emission spectrometry (AES) was used to determine Ca, Mn, and Fe. The matrix Ca is present in a concentration range from 1600 to 1300 g/g and the major impurities Mn and Fe are 152-32 and 100-28 g/g, respectively. The detection limits of ICP-MS for REE are found to be better by two orders of magnitude than for ICP-AES. A commercially available SCIEX Elan ICP-MS with additional software was used to make mathematical corrections for isobaric interferences and molecular ions.Presented in part at the 1989 European Winter Conference on Plasma Spectrochemistry, Reutte, Austria     

Comparative studies on metal determination in airborne particulates by LA-ICP-MS and furnace atomization non-thermal excitation spectrometry

Air pollution, especially by metallic aerosols, has toxic effects on soil and water, biological environment, and human health. Therefore the determination of metal contents in airborne dust is of particular relevance. For measurements with high resolution in time and space a rapid analytical method is necessary as well as short and efficient sampling. Two techniques for rapid multielement trace analysis were compared with respect to the determination of metallic, aerosol concentration in air. In both methods air was sucked through a filter material which subsequently was analyzed without any additional pretreatment. When La-ICP-MS was applied, quartz fibre filters were used as collectors which were then ablated employing a Nd:YAG laser for analyses by ICP-MS. With FANES a special porous graphite tube acted as an efficient particle collector. When inserted into the FANES source the graphite tube simultaneously serves as thermal atomizer and hollow cathode so that collected particulates were vaporized and excited in the tube for optical emission spectrometry. For signal registration an echelle polychromator was used. With FANES detection limits based on the 3 -criterion range between 0.2 and 2 ng/m³ for 10 elements. With quartz filters comparable results can be obtained only after enrichment by more than a 500-fold air volume. Measured metallic aerosol concentrations in ambient air by both methods do not differ within the 95% significance level.     

Isotope dilution gas chromatography/mass spectrometry for platinum determination in urine

The therapeutic importance of platinum (Pt) compounds, the growing accessibility of gas chromatography/mass spectrometry (GC/MS) systems in clinical laboratories, and the lack of a mass spectrometric method for the determination of Pt in biological samples motivated us to develop an isotope dilution GC/MS assay for Pt. The method is based on the use of lithium bis(trifluoroethyl) dithiocarbamate, Li(FDEDTC), as a chelating agent and enriched ¹⁹²Pt for isotope dilution. Conditions were optimized for the precise and accurate determination of isotope ratios of Pt by using a 10-m DB-l fused silica capillary column and a reverse-geometry double-focusing mass spectrometer with selected ion monitoring. An overall precision of 1% was obtained by combining within-run precision and between-run precision at the 10-ng level. No appreciable memory effect was observed when samples with different isotope ratios were analyzed sequentially. The method was validated by the quantitation of Pt in National Institute of Standards and Technology freeze-dried urine sample SRM 2670. A concentration value of 125 ± 6 /Lg/L (n = 6) was obtained by using four different sets of isotope ratios in the molecular ion and supports the National Institute of Standards and Technology recommended value of 120 ± ? μg/L. Limits-of-quantitation, estimated at 3 μg/L, are made possible by the high sensitivity of the method and the low blank value for Pt.