Isotope Dilution Mass Spectrometry Analysis Research Articles

Verification measurements of the IRMM-1027 and the IAEA large-sized dried (LSD) spikes

In the frame of the accountancy measurements of the fissile materials, reliable determinations of the plutonium and uranium content in spent nuclear fuel are required to comply with international safeguards agreements. Large-sized dried (LSD) spikes of enriched 235U and 239Pu for isotope dilution mass spectrometry (IDMS) analysis are routinely applied in reprocessing plants for this purpose. A correct characterisation of these elements is a pre-requirement for achieving high accuracy in IDMS analyses. This paper will present the results of external verification measurements of such LSD spikes performed by the European Commission and the International Atomic Energy Agency.

Reduction of hexavalent chromium by fasted and fed human gastric fluid. II. Ex vivo gastric reduction modeling

To extend previous models of hexavalent chromium [Cr(VI)] reduction by gastric fluid (GF), ex vivo experiments were conducted to address data gaps and limitations identified with respect to (1) GF dilution in the model; (2) reduction of Cr(VI) in fed human GF samples; (3) the number of Cr(VI) reduction pools present in human GF under fed, fasted, and proton pump inhibitor (PPI)-use conditions; and (4) an appropriate form for the pH-dependence of Cr(VI) reduction rate constants. Rates and capacities of Cr(VI) reduction were characterized in gastric contents from fed and fasted volunteers, and from fasted pre-operative patients treated with PPIs. Reduction capacities were first estimated over a 4-h reduction period. Once reduction capacity was established, a dual-spike approach was used in speciated isotope dilution mass spectrometry analyses to characterize the concentration-dependence of the 2nd order reduction rate constants. These data, when combined with previously collected data, were well described by a three-pool model (pool 1 = fast reaction with low capacity; pool 2 = slow reaction with higher capacity; pool 3 = very slow reaction with higher capacity) using pH-dependent rate constants characterized by a piecewise, log-linear relationship. These data indicate that human gastric samples, like those collected from rats and mice, contain multiple pools of reducing agents, and low concentrations of Cr(VI) (<0.7 mg/L) are reduced more rapidly than high concentrations. The data and revised modeling results herein provide improved characterization of Cr(VI) gastric reduction kinetics, critical for Cr(VI) pharmacokinetic modeling and human health risk assessment.

Human C-peptide Quantitation by LC-MS Isotope-Dilution Assay in Serum or Urine Samples.

In this communication we report a simple and efficient approach to C-peptide quantitation using isotope dilution mass-spectrometry analysis. The method facilitates quantitation of C-peptide levels at least one order of magnitude lower compared to concentration levels achieved with an IDA method reported previously. The improvement was due to more intensive sample preparation procedure that, in turn, makes it possible to increase the sample load without a corresponding increase in matrix effects. We also show the results of a comparison study with a second laboratory using a similar previously reported method for C-peptide quantitation.

Application of Isotope Dilution Gas Chromatography−Mass Spectrometry in Analysis of Organochlorine Pesticide Residues in Ginseng Root

A highly accurate and precise method based on isotope dilution gas chromatography-mass spectrometry was developed for the determination of five matrix-bound organochlorine pesticides, namely, hexachlorobenzene and hexachlorocyclohexanes (alpha-, beta-, delta-, and gamma- isomers), in a reference sample of Panax gingseng. Identification of the analytes was confirmed under selective ion monitoring mode by the presence of two dominant ion fragments within the specific time windows (+/-1% of the relative retention time with respect to the calibration standards) and matching of relative ion intensities of the concerned ions in samples and calibration standards (within +/-5%). Quantification was based on the measurement of concentration ratios of the natural and isotopic analogues in the sample and calibration blends. To circumvent the tedious iterative process of exact isotope matching that is often used in isotope dilution mass spectrometry analysis, a single-point calibration procedure was adopted with the isotopic amount ratios in the sample and calibration blends close to unity (0.9-1.1). Under the described approach, intraday and interday repeatability of replicate analyses of organochlorine pesticides in the ginseng root sample were below 1.4%. The expanded relative uncertainty ranging from 4.0 to 6.5% at a coverage factor of 2 was significantly lower than those of conventional gas chromatographic methods using other calibration techniques (internal or external standards). A deviation of less than 2.0% from the certified values was achieved when applying the developed method to determine hexachlorobenzene, alpha-, and beta-hexachlorocyclohexane in a certified reference material (CRM), BCR-CRM 115. Because of the unavailability of relevant CRMs of herbal origins, the concerned ginseng root sample, after verification of the "true values" of the concerned organochlorine pesticides by the valid primary method, is suitable for serving as an in-house reference material for quality assurance and method validation purposes.

Stable Isotope Dilution Mass Spectrometry Analysis of Endogenous and Synthetic Corticosteroids for the Pharmacokinetic and in vivo Metabolic Investigations in Humans

This review article underlines the importance of stable isotope dilution mass spectrometry analysis of endogenous and synthetic corticosteroids for the pharmacokinetic and in vivo metabolic investigations in humans. The multi-labeled corticosteroids with stable isotopes such as [1,2,4,19-13C4]cortisol, [1,2,3,4-13C4]cortisol, [1,1,19,19,19- 2H5]cortisol, [9,11,12,12-2H4]cortisol, etc. have been used not only as analytical internal standard for the mass spectrometry but as tracer in the pharmacokinetic and metabolic studies in human in vivo. Stable isotope dilution analysis of cortisol metabolites (tetrahydrocortisol (THF), allo-tetrahydrocortisol (allo-THF), tetrahydrocortisone (THE), and 6β - hydroxycortisol (6β-OHF)) and synthetic corticosteroids (prednisolone, prednisone, budesonide, fluticasone, etc.) is also the subject of this review. In the gas chromatographic mass spectrometric (GC-MS) analysis of corticosteroids, it is usual to employ derivatives in which some or all of the original functional groups are protected. Thermal stabilization of corticosteroids in the analysis has been achieved most successfully by formation of methoxime-trimethylsilyl (MO-TMS) derivatives. Bismethylenedioxy-pentafluoropropionyl (BMD-PFP) derivatives have been developed to simultaneously measure cortisol, cortisone, and their tetrahydrocorticoid metabolites (THF, allo-THF, and THE) and/or prednisolone and prednisone in plasma and urine. Stable isotope tracer methodology has been applied to the measurements of cortisol production rate, determination of human urinary cortisol metabolites, and assessment of in vivo activities of 11β- hydroxysteroid dehydrogenase (11β-HSD) in humans. This methodology also has been used for the validity of endogenous cortisol 6β-hydroxylation clearance as a new index for phenotyping the in vivo cytochrome P450 3A (CYP3A) in humans. Keywords: Stable isotope, Label, Cortisol, Corticosteroid, Mass spectrometry

Simultaneous speciation of mercury and butyltin compounds in natural waters and snow by propylation and species-specific isotope dilution mass spectrometry analysis

A robust method has been developed for simultaneous determination of mercury and butyltin compounds in aqueous samples. This method is capable of providing accurate results for analyte concentrations in the picogram per liter to nanogram per liter range. The simultaneous determination of the mercury and tin compounds is achieved by species-specific isotope dilution, derivatization, and gas chromatography-inductively coupled plasma mass spectrometer (GC-ICP-MS). In derivatization by ethylation and propylation, reaction conditions such as pH and the effect of chloride were carefully studied. Ethylation was found to be more sensitive to matrix effects, especially for mercury compounds. Propylation was thus the preferred derivatization method for simultaneous determination of organomercury and organotin compounds in environmental samples. The analytical method is highly accurate and precise, with RSD values of 1 and 3% for analyte concentrations in the picogram per liter to nanogram per liter range. By use of cleaning procedures and SIDMS blank measurements, detection limits in the range 10-60 pg L(-1) were achieved; these are suitable for determination of background levels of these contaminants in environmental samples. This was demonstrated by using the method for analysis of real snow and seawater samples. This work illustrates the great advantage of species-specific isotope dilution for the validation of an analytical speciation method-the possibility of overcoming species transformations and non-quantitative recovery. Analysis time is saved by use of the simultaneous method, because of the use of a single sample-preparation procedure and one analysis.

Synthesis and characterization of isotopically enriched methylmercury (CH3201Hg+)

AbstractA simple procedure for the synthesis of an important standard, isotopically enriched methylmercury, which is not commercially available, has been established successfully. The isotopically enriched standard synthesized is utilized in conventional isotope dilution mass spectrometry (IDMS), as well as in speciated IDMS (SIDMS), for determination of the true concentration of methylmercury in environmental samples. The CH3201Hg+ standard has been synthesized from commercially available 201HgO and tetramethyltin. The synthesis time required is 1 h at 60°C. The product is highly pure, yielding more than 90% as 201Hg in CH3201Hg+. Hazardous dimethylmercury does not occur during this synthesis procedure. The product synthesized was analyzed using high‐performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (ICP‐MS) and ICP‐MS alone in order to determine its concentration, isotopic composition and purity. The stability of the product was also evaluated for over 6 months and found to be stable at 4°C in the dark. The isotopically enriched methylmercury synthesized can be used in SIDMS and IDMS analyses as a standard. Copyright © 2003 John Wiley &amp; Sons, Ltd.

Negative thermal ionization mass spectrometry of selenium part 4. Selenium trace determination in sediments and related samples

Selenium traces have been determined in different sediments (estuarine, river, lake), sandy soil and sewage sludge with isotope dilution mass spectrometry (IDMS). Negative selenium atomic ions are formed in a double-filament thermal ion source. The use of a silica gel technique for ionization improves the mass spectrometric sensitivity by a factor of 40 compared with the technique previously applied. An enriched82Se spike is used for the isotope dilution process. The samples are decomposed with a mixture of conc. HNO3 and conc. HE After decomposition selenium is separated by the formation of SeH2 in a hydride generation system which is normally applied for atomic absorption spectrometry. The IDMS results for three standard reference sediments agree well with the certified values. In the case of three other standard reference materials, which are not certified for selenium up to now, the IDMS analyses were able to improve the selenium data given for information or as indicative values. The precision of the IDMS method in the concentration range of 0.2–3.5 μg/g lies between 0.8 % and 4.1 %. The detection limit is 6 ng/g. A comparison with several other methods shows that IDMS is one of the very few analytical methods which produces accurate selenium results even at concentration levels of 0.2 μg/g and less in sediments and related samples of environmental interest.