Stable Isotope Dilution Analysis Research Articles

Quantitative trace element analysis of microdroplet residues by secondary ion mass spectrometry.

This paper reports the results of secondary ion mass spectrometry (SIMS) analyses of the elemental components contained in microvolume liquid residues deposited onto high-purity graphite substrates. These residues were formed by evaporating the solvent in 25-nL volumes of standard solutions containing the analyte element and a known mass of a yttrium internal standard. The capability of the SIMS technique to quantitatively measure the mass of the analyte was determined from these standard samples. The relative ion yields of Al, Ca, Mn, Fe, Co, Cu, An, Se, and Pb with respect to the Y internal standard were determined. The minimum detectable quantities (MDQ) of these elements were measured along with the precision of the SIMS analysis. Gram detectivities for this set of elements dissolved in the 25-nL volumes ranged between 85 pg and 2.0 fg, corresponding to molar detectivities ranging between 16 ..mu..M and 1.6 nM. Stable isotope dilution analysis of samples containing enriched /sup 206/Pb demonstrated quantitative measurement accuracy within 3% of the true values for samples containing 4.0 mM Pb. SIMS analyses of the NBS bovine serum reference standard indicate that this technique can provide useful quantitative analysis of selected elements contained in a microvolume of biological fluids.

Stable isotope dilution analysis of succinylacetone using electron capture negative ion mass fragmentography: an accurate approach to the pre- and neonatal diagnosis of hereditary tyrosinemia type I

A sensitive and accurate isotope dilution assay using electron capture negative ion mass fragmentography was developed for succinylacetone in amniotic fluid, plasma and urine. The method utilizes (D 4)-5(3)-methyl-3(5)-isoxasole propionic acid as internal standard. Sample pretreatment consisted of oximation at pH < 2 to 5(3)-methyl-3(5)-isoxasole propionic acid, clean up using liquid partition chromatography and further derivatization to the pentafluorobenzyl ester. Control values in plasma revealed a mean x ̄ = 0.044 μ mol/l , range = 0.005−0.163 μmol/l, in urine x ̄ = 0.15 μ mol/l , range 0.01–0.40 μmol/l corresponding to x ̄ = 0.03 μ mol/mmol creat., range 0.01–0.14 μmol/mmol creat., and in amniotic fluid x ̄ = 0.016 μ mol/l , range = 0.001−;0.030 μmol/l. The utility of the method was demonstrated by quantification of succinylacetone in urine from patients with hereditary tyrosinemia type I ( n = 8, excretion range 2.60–493.3 μmol/l corresponding to 0.67–197.3 μmol/mmol creat.) and in two amniotic fluid samples from fetuses affected with this disorder (concentration of succinylacetone 0.085 and 1.50 μmol/l, respectively). Maternal urine from a woman carrying an affected fetus did not show elevated urinary succinylacetone excretion.

Synthesis of deuterium labelled analogues of very long chain fatty acids C22:0, C24:0 and C26:0 for use as internal standards in stable isotope dilution analysis

Synthesis of deuterium labelled analogues of very long chain fatty acids C22:0, C24:0 and C26:0 for use as internal standards in stable isotope dilution analysis

Synthesis of deuterium labelled analogues of pristanic acid and phytanic acid for use as internal standards in stable isotope dilution analysis

Synthesis of deuterium labelled analogues of pristanic acid and phytanic acid for use as internal standards in stable isotope dilution analysis

Measurement of stable isotopes of bromine in biological fluids with inductively coupled plasma mass spectrometry.

A method is reported for the accurate measurement of the two stable isotopes of bromine in biological fluids of interest in human metabolic studies. The method is based on inductively coupled plasma mass spectrometry (ICP-MS).It is shown that the background ion beam intensities at m/z= 79 and 81 are typically in the range 70–335 and 600–7200 ions s–1, respectively, when de-ionised water is aspirated into the plasma. The corresponding range for 1.0 µg ml–1 of natural Br is 9700–18 500 ions s–1 at m/z= 79. The detection limit (3[graphic omitted]) for Br is in the range 2–5 ng ml–1. A method is given for automatic correction of the argon contribution at m/z= 81.Data are presented which show that the isotope ratio 81Br/79Br can be measured routinely with a precision (relative standard deviation) of 1% or better. The measured ratio is independent of the Br concentration in the range 3–20 µg ml–1. Linear regression equations are obtained for stable isotope calibration graphs over the range 0.997–5.322 (MIR81/79). However, the slopes of these plots deviate considerably from the expected value of one.Two chemical separation schemes are described, Scheme I, based on cation exchange and Scheme II, based on distillation from acidified solutions. The former is applicable to plasma (and possibly saliva) samples whereas the latter is successful for urine. The presence of large amounts of sulphate produces significant enhancement of the ion intensity at m/z= 81 (due to 32S16O31H+). Distillation permits the required separation of Br from sulphate, whereas precipitation with Ba(NO3)2 does not appear to be satisfactory.Application of the method of standard additions and stable isotope dilution analysis to samples of urine from several subjects indicates that this method permits quantitative analysis of bromine to be carried out with a precision (and accuracy) of about 2%.

Stable isotope dilution analysis of hydrologic samples by inductively coupled plasma mass spectrometry

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStable isotope dilution analysis of hydrologic samples by inductively coupled plasma mass spectrometryJohn R. Garbarino and Howard E. TaylorCite this: Anal. Chem. 1987, 59, 11, 1568–1575Publication Date (Print):June 1, 1987Publication History Published online1 May 2002Published inissue 1 June 1987https://doi.org/10.1021/ac00138a018RIGHTS & PERMISSIONSArticle Views90Altmetric-Citations60LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts Get e-Alerts

Stable isotope dilution analysis of isovalerylglycine in amniotic fluid and urine and its application for the prenatal diagnosis of isovaleric acidemia.

A stable isotope dilution method was developed to measure accurately small amounts of isovalerylglycine in amniotic fluid and urine for the prenatal diagnosis of isovaleric acidemia. [4,4,4-D3]Isovalerylglycine was synthesized and used as an internal standard. Samples were extracted, methylated, and analyzed by chemical ionization gas chromatography-mass spectrometry operated in the selected ion monitoring mode. This method is very sensitive (lower limit approximately 5 ng/ml), linear over three orders of magnitude above 10 ng/ml up to at least 10 micrograms/ml and reproducible. No isovalerylglycine was detected at all in amniotic fluids from eleven normal pregnant women with an exception of a single case which contained 6 ng/ml. Amniotic fluids from five pregnancies at risk were analyzed. Two of these samples had isovalerylglycine concentrations of 957 and 556 ng/ml. Three others contained 18, 18, and 17 ng/ml of isovalerylglycine. Postpartum diagnostic tests and/or in vitro assay of isovaleryl-CoA dehydrogenase of [1-14C] isovaleric acid oxidation using amniocytes confirmed that the first two fetuses were affected by isovaleric acidemia, whereas the latter three were unaffected. The method described in this report provides a highly accurate and reliable technique for the prenatal diagnosis of isovaleric acidemia.

Stable isotope dilution analysis of orotic acid and uracil in amniotic fluid

Rapid, sensitive and accurate stable isotope dilution assays were developed for the measurement of orotic acid and uracil in amniotic fluid. The method utilizes [ 15N 2]orotic acid and [ 15N 2]uracil as internal standards, isolation by liquid partition chromatography and quantitation by chemical ionization selected ion monitoring gas chromatography-mass spectrometry. Orotic acid at a concentration of 0.26 ± 0.05 μmol/1 and uracil at a concentration of 0.55 ± 0.13 μmol/l were detectable in normal amniotic fluid. As affected fetuses with argininosuccinate synthetase or ornithine carbamoyl transferase deficiency showed no significant elevation of orotic acid and/or uracil in their surrounding amniotic fluids, this method unfortunately seemed not to be useful for prenatal diagnosis of these inherited disorders. Nevertheless, it provides significant advantage over available methods for the quantitation of orotic acid and uracil in which the analysis of these compounds must be very accurate, highly specific and sensitive (e.g. detection of heterozygosity for omithine carbamoyl transferase deficiency).

Stable isotope dilution analysis of galactitol in amniotic fluid: an accurate approach to the prenatal diagnosis of galactosemia.

A stable isotope dilution assay for galactitol in amniotic fluid has been developed using selected ion monitoring chemical ionization gas chromatography-mass spectrometry of the hexaacetate derivative. [1,1-2H2]Galactitol was synthesized for use as the internal standard. Galactitol is a component of normal amniotic fluid with a mean concentration of 0.70 +/- 0.18 mumol/liter (n = 5). The amniotic fluid of a fetus with galactosemia had a concentration of 7.96 mumol/liter. Mannitol, sorbitol, and inositol were also found to be normal constituents of amniotic fluid. This stable isotope dilution assay is a rapid accurate method for measurement of galactitol in amniotic fluid for prenatal diagnosis of galactosemia.

Stable isotope dilution analysis by thermal ionization mass spectrometry (II): The determination of cadmium and copper

The combination of stable isotope dilution analysis (SIDA) and thermal ionization mass spectrometry (TIMS) is in use for lead and uranium determination at milligram per kilogram levels for over 20 years. However, several other elements can also be determined accurately by SIDA/TIMS. In this study the determinations of cadmium and copper are described. Details of the digestion, electrochemical and ion-exchange separations and the loading of the elements on a filament are given. The advantages of the SIDA/TIMS technique are shown and illustrated with results for several certified reference materials.

Stable isotope dilution analysis of 3-hydroxyisovaleric acid in amniotic fluid: contribution to the prenatal diagnosis of inherited disorders of leucine catabolism.

A quantitative assay for 3-hydroxyisovaleric acid in amniotic fluid was developed using D6-3-hydroxyisovaleric acid as an internal standard. 3-Hydroxyisovaleric acid was isolated by liquid partition chromatography and the amount determined by selected ion monitoring, ammonia chemical ionization gas chromatography-mass spectrometry of the trimethylsilyl derivatives. The concentration of 3-hydroxyisovaleric acid in ten normal amniotic fluid was 4.52 +/- 1.73 mumol/l. The level was elevated eight-fold in the amniotic fluid from a pregnancy resulting in the birth of a child with biotin-responsive multiple carboxylase deficiency. The stable isotope dilution assay of 3-hydroxyisovaleric acid in amniotic fluid is a rapid, sensitive and accurate method for the prenatal diagnosis of this disorder, and may be of value in the prenatal diagnosis of other inherited disorders of leucine catabolism.

Quantification of alkaline-earth metals in rabbit fetuses during the last two weeks of gestation by field desorption mass spectrometry

The fetal rabbit organs eye, brain, kidney, lung, heart and liver from the third and fourth weeks of gestation were investigated. Quantitative determination of the alkaline earth ions magnesium, calcium, strontium and barium was carried out using field desorption mass spectrometry and stable isotope dilution analysis. It was established that in the course of organ differentiation processes the metal concentrations fall markedly. This fact is related to the simultaneous fall in extracellular liquids. In the fourth week of gestation the concentrations of the alkaline earth ions reach a level in the rabbit fetus which is comparable to the physiologically normal level in other vertebrates.

Lead Poisoning From Retained Bullets

Lead intoxication (plumbism) from retained bullets has rarely been reported but may be fatal if unrecognized. Bullets lodged within joint spaces or pseudocysts are more likely to develop this complication, although patients with retained missiles in other locations may also be at risk. Subtle findings such as the occurrence of unexplained anemia, abdominal colic, nephropathy, or neurologic deterioration in patients with retained missiles may suggest consideration of plumbism. An intercurrent metabolic stress such as infection, endocrinopathy, or alcoholism may be a precipitating factor. Among the various diagnostic studies available, mass spectrometric stable isotope dilution analysis may be the most reliable. It is important to employ chelation therapy prior to any operative intervention. This will reduce the mobilization of lead from bone during or following the surgical procedure.

“Stable Isotope Mixing”, a Proposal to Analyze Stable Isotopes Using a Technique Similar to the Isotope Dilution Analysis

A proposal (shortly expressed as stable isotope mixing) similar to the stable isotope dilution analysis is described. It deals with the determination of the stable isotope relative abundances. Seve...

Long-term urinary excretion of methaqualone in a human subject.

The urinary excretion rates of methaqualone and of one of its metabolites, 6-hydroxymethaqualone (free and conjugated), were determined in a normal male subject over a 30-day period by stable isotope dilution analysis using field ionization mass spectrometry. The excretion rates for methaqualone were fitted by computer to three-and four-exponential functions. The estimated terminal halflife for the drug was approximately 74 hr. 6-Hydroxymethaqualone excretion in the elimination phase was fitted to a single exponential decay curve. Estimated halflives obtained for the free and total (primarily conjugated) metabolite were 78 and 70 hr, respectively. The apparent difference between the latter two values was not statistically significant. The close similarity between the halflives of methaqualone and 6-hydroxymethaqualone indicates that elimination of these compounds is ratelimited by the same pharmacokinetic process. A similarly long halflife, 50 hr, was estimated in a previous study (5) of another subject in which excretion of the compounds was followed over an 11-day period. These results demonstrate that the half-life of methaqualone can be much longer than has been indicated by relatively short-term investigations.

N-Hydroxylation of 1-(2,5-demethoxy-4-methylphenyl)-2-aminopropane by rabbit liver microsomes.

Metabolic N-hydroxylation of the potent psychotomimetic amine 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (5) by rabbit liver microsomal preparations has been investigated. Synthetic hydroxylamine 8 was obtained by sequential reduction of the corresponding nitropropene 10 with sodium borohydride followed by zinc reduction of the resulting nitropropane 11. Compound 8 in water (pH 7.4) was rapidly air oxidized to oxime 12; this oxidation was completely blocked by rabbit liver microsomes. Microsomal incubations of amine 5 or its bis(methoxy-d3)hexadeuterio analog 5-d6 resulted in the formation of 8 and 8-d6, respectively, identified as their bis(trifluoroacetyl) derivatives by GLC-MS. Quantitative estimations of metabolite formation employing selected ion monitoring with the aid of an accelerating voltage alternator were accomplished by stable isotope dilution analyses with 5-d6 as substrate and 8-d0 as internal standard. Similar analyses starting with "pseudoracemates" (R)-5-d0:(S)-5-d6 or (R)-5-d6:(S)-5-d0 as substrates established metabolite 8 to be enriched with its R enantiomer.

Luna 20 and Apollo 16 core fines: large-ion lithophile trace-element abundances

Li, K, Rb and Sr abundances have been determined by mass-spectrometric stable isotope dilution analysis for a sample of Luna 20 fines and for eight fines from the Apollo 16 deep drill core. Ba and rare-earth abundances have also been determined for the Luna 20 sample and two of the Apollo 16 samples. Luna 20 and Apollo 16 were the first missions to interior highlands sites. The trace-element similarity of the fines samples may indicate that the lunar highlands are fairly homogeneous. An abundant feldspathic component is indicated. However, the negative Eu anomalies indicate that the fines cannot have been made entirely from earthly feldspathic cumulates. As in the case of the Apollo 12 and 15 core samples, the abundance of the large-ion lithophile trace elements increases with depth in the Apollo 16 core. It is suggested that Apollo 16 core material was lost during separation of the drill sections on the Moon.

Atomic absorption spectrophotometry of rubidium in rocks and minerals - comparison with isotope dilution

Rubidium at a concentration of between ∼0.5 and ∼3 ppm has been determined in rocks and minerals by atomic absorption spectrophotometry. By comparison with external standards a precision of better than 3% has been attained without recourse to chemical separation of rubidium. Lanthanum and potassium buffers were added to the standards and samples to compensate for interferences. Very favourable agreement was obtained between the concentration of rubidium as determined by atomic absorption when compared to measurements made by stable isotope dilution analysis.

Isotopic Ages from Some Spitsbergen Rocks

ISOTOPIC ages by potassium – argon and rubidium – strontium methods have been measured on some Spitsbergen rocks, in the hope of contributing to the Mid-Palaegeozoic time-scale and to the understanding of local geological history1. Rubidium, strontium and argon measurements were made by stable isotope dilution analysis, except for York's figure, which was by total volume (argon) measurement. The potassium measurements were made by flame photometer.

Rb-Sr analyses and age determinations of certain lepidolites, including an international interlaboratory comparison suite

Rb, Sr and radiogenic ⁸⁷ SR concentrations, and radioactivity "ages" have been determined by stable isotope dilution for lepidolite samples from 8 pegmatite occurrences. Five of the samples analyzed comprise an "intercomparison suite" ranging in age from 100 X 10 ⁶ to 2600 X 10 ⁶ years. Portions of these samples were sent by us to several other laboratories for analysis, as a test of the interlaboratory reproducibility of stable isotope dilution analysis. In this paper analytical data for this suite from 4 laboratories are compared. Interlaboratory reproducibility and intralaboratory reproducibility are essentially identical for the age determinations; it is apparent that age ratios for lepidolite can be measured routinely with analytical accuracy better than + or - 4% (standard deviation). Rb was determined with a precision of 1 to 2%, and Sr with a precision of 1 to 3% within individual laboratories; difference between results obtained at the several laboratories may be due in part to small differences in Rb and Sr standard solution calibrations and in part to sample inhomogeneities; the good interlaboratory agreement in age determinations favors the latter interpretation. A comparison of stable isotope dilution, optical spectrographic, and neutron activation Rb/Sr data for sets of independently collected and analyzed samples from 6 localities is also given. For each pegmatite, there is good agreement (a range of a few percent) in the ages determined by isotope dilution and neutron activation, although Rb concentrations have ranges of up to 30%. The study gives insight into the sources of error in the optical spectrographic technique and provides standards which may make possible the improvement of this method of analysis.