The measuring procedure and corrections for the high-precision mass-spectrometric analysis of isotopic abundance ratios, especially referring to carbon, oxygen and nitrogen

doi:10.1016/0020-7381(73)80044-0

International Journal of Mass Spectrometry and Ion Physics

Volume 12, Issue 3, October 1973, Pages 273-298

https://doi.org/10.1016/0020-7381(73)80044-0 Get rights and content

Abstract

In order to determine isotopic abundance ratios such as ¹³C/¹²C, ¹⁸O/¹⁶O or ¹⁵N/¹⁴N, a mass spectrometer reads the ratio of the voltages which are generated by the isotopic ion beams, trapped by a double collector system.

The effect of the gas inlet pressure on the voltage ratio in the case of nitrogen and carbon dioxide is determined experimentally, using a Varian M86. A knowledge of this pressure dependence provides a method of determining the voltage ratio, which is independent of the inlet pressure.

This paper partly reviews the work of Craig and gives a detailed treatment of the measuring procedure, of the corrections to be applied to the voltage ratios, viz. for pressure effects, of the way in which the voltage ratios are transformed into isotopic abundances, and of disturbing factors such as spectrometer background and sample contamination.

The corrections will be discussed successively in the order in which they are to be applied. In every case the exact equation is deduced, while often an approximation is given for use with natural samples.

The major contributions to the technique of mass-spectrometric analysis of isotopic abundance ratios are due to Craig (1957) and Dansgaard (1961). The original choice of the latter to use absolute differences between a sample and standard, rather than relative, has been abandoned. Craig made in his correction formula approximations applicable to samples deviating not more than a few percent from the standard and based on an accuracy of 0.1‰, while nowadays the precision is often better than that. Consequently, we thought it necessary to review the whole procedure and make revisions, where necessary.

Although the stable isotopes of carbon, oxygen and nitrogen in CO₂ and N₂ respectively are specifically dealt with, the general equations also apply to isotopic analyses on other gases, such as argon (³⁶Ar/⁴⁰Ar) and SO₂ (³⁴S/³²S).

References (14)

J. Kistemaker
Physica
(1952)
A.J.H. Boerboom et al.
Physica
(1958)
H. Craig
Geochim. Cosmochim. Acta
(1957)
C. Brunnée et al.
(1964)
P.M. Grootes and W.G. Mook, Int. J. Mass Spectrom. Ion Phys., to be...
W. Dansgaard
Meddel. Grønl.
(1961)
H. Friedrichsen, personal communication,...

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The test meal consisted of 20 g of fat and 200 mg of 13C-labeled mixed triglycerides consisting of naturally occurring long-chain fatty acids (Chlorella Industry Co., LTD, Tokyo, Japan). Enrichment of 13CO2/12CO2 in the collected breath samples was measured by infrared spectrophotometry with an Otsuka Ubit-IR 300 (Otsuka Electronics, Osaka, Japan), and the results were expressed in accordance with the Pee Dee Belemnite international standard, as described previously.26,27 Cumulative percentages of label recovery (% dose 13C cum) were calculated using the trapezoidal rule.
Pancreatectomy, including pancreatoduodenectomy and distal pancreatectomy, often causes postoperative pancreatic exocrine insufficiency (PEI). Our aim was to clarify a relationship between remnant pancreatic volume and postoperative PEI.
A total of 227 patients who underwent pancreatoduodenectomy or distal pancreatectomy were enrolled in this study. All patients underwent a ¹³C-labeled mixed triglyceride breath test to assess pancreatic exocrine function and abdominal dynamic computed tomography for assessing remnant pancreatic volume after pancreatectomy at a median of 7 months postoperatively. The percent ¹³CO₂ cumulative dose at 7 hours (% dose ¹³C cum 7 h) < 5% on the ¹³C-labeled mixed triglyceride breath test was considered diagnostic of postoperative PEI. Relationships between postoperative PEI and clinicopathologic factors including remnant pancreatic volume were analyzed.
Pancreatoduodenectomy and distal pancreatectomy were performed in 174 (76.7%) and 53 (23.3%) patients, respectively. Of the 227 patients, 128 (56.3%) developed postoperative PEI. Postoperative % dose ¹³C cum 7 h was strongly correlated with remnant pancreatic volume (r = .509, P < .001). The cut-off value of remnant pancreatic volume for predicting postoperative PEI was 24.1 mL by receiver operating characteristic curve analysis. Multivariate analysis revealed that remnant pancreatic volume < 24.1 mL was the only independent predictive factor for the development of postoperative PEI in patients who underwent pancreatectomy (P < .001, hazard ratio; 5.94, 95% confidence interval; 2.96–12.3).
Remnant pancreatic volume is associated closely with postoperative PEI after pancreatectomy. Remnant pancreatic volume may predict postoperative PEI in patients who undergo pancreatectomy.
The Stable Isotopic Composition of Atmospheric CO2
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About half of the CO₂ emitted by fossil fuel combustion currently remains in the atmosphere. The other half is removed by CO₂ uptake on land and in the ocean. Prediction of future CO₂ concentrations relies critically on the understanding of these sources and sinks and their potential variability over time. While such understanding requires quantification of individual carbon fluxes, the means to achieve this in direct measurements are very limited. The isotopic composition of atmospheric CO₂ provides a powerful and indispensable tool in that respect. This chapter reviews the methodological and observational basis underlying the use of the isotopic composition of atmospheric CO₂ in tracing and interpreting the changes in sources and sinks of CO₂ over seasonal, annual, and longer timescales, as well as over different spatial scales. The processes influencing the isotopic ‘signatures’ associated with specific processes in the contemporary carbon cycle and the usefulness of such signals are discussed. For example: How can annual-scale variations in ¹³C observations be used to partition CO₂ uptake between land and ocean? Why does the decreasing trend in the ¹³C of atmospheric CO₂ over the past 150 years (due to the addition of ¹³C-depleted CO₂ to the atmosphere through fossil fuel combustion) provide an indicator of the carbon turnover rate in the biosphere? Why does the ¹⁸O in atmospheric CO₂ reflect variability in the plant versus soil fluxes within the land biosphere? Finally, the new frontiers in the application of isotopic analysis of atmospheric CO₂, such as the use of laser spectroscopy, our ability to identify variations in the rare, isotopically doubly labeled CO₂ molecules (e.g., containing both ¹³C and ¹⁸O), and the measurement of the ¹⁷O anomaly in CO₂, are explored.
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Although numerous non-invasive tests are currently available to explore liver function and disease activity in patients with HCV-related chronic diseases, none of these indicate the likelihood of disease progression in the individual patient.
We aimed at assessing the prognostic ability of ¹³C₂-aminopyrine breath test (¹³C-ABT) in the prediction of liver fibrosis progression in patients with HCV chronic hepatitis who prospectively entered a long-term follow-up.
Fifty patients with HCV-related chronic disease who underwent paired liver biopsy (at baseline and after a mean period of 86 months) were included in the study. ¹³C-ABT was carried out at baseline and every 3 years. Histological progression was defined as increase of at least 2 fibrosis units according to Ishak score.
Fourteen patients progressed of at least 2 fibrosis units during the follow-up. These patients were more frequently infected with a HCV-1b genotype and had, at baseline, a significantly older age, higher BMI, AST levels, and AST to platelet ratio index (APRI). ¹³C-ABT was altered in 57% of cases at baseline and in 100% of the cases at 3-year follow-up. In the univariate analysis, age (p = 0.005), BMI (p = 0.006), platelet count (p = 0.03), AST (p = 0.012) and ALT (p = 0.04) levels, APRI (p = 0.03), and baseline ¹³C-ABT results (p <0.0001) were all independently associated with progression of liver fibrosis. By Cox’s multiple regression analysis, the ¹³C-ABT was the only covariate that significantly predicted liver fibrosis progression (HR 6.7; 95% CI 2.3–20.1; p <0.001).
¹³C-ABT accurately predicts the risk of disease progression in patients with HCV-related chronic hepatitis.
Reduced pancreatic parenchymal thickness indicates exocrine pancreatic insufficiency after pancreatoduodenectomy
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Citation Excerpt :
It is 97.3% uniformly labeled, thereby facilitating the use of small tracer doses for generating 13CO2 abundances in the breath that are within the detectable range. All subjects were studied under resting conditions after an overnight fast of at least 12 h. Baseline breath samples were obtained before the meals into a specially designed collection bag (retention volume 1300 mL, supplied by Otsuka Pharmaceutical, Tokyo, Japan), and postprandial breath samples were taken in the collection bag (retention volume 250 mL) every hour after the meal for 7 h. Enrichment of 13CO2/12CO2 in the breath samples was measured by infrared spectrophotometry using POCone (Otuka Electronics, Tokyo, Japan), and results were expressed as values (referring to the Pee Dee Belemnite International Standard), as described previously [9, 10]. Results were expressed as parts per thousand excess of δ13CO2 (Δ13CO2).
The aim of this study was to investigate whether perioperative morphologic characteristics are predictive of exocrine pancreatic function after pylorus-preserving pancreatoduodenectomy (PPPD) with pancreaticogastrostomy.
A ¹³C-labeled mixed triglyceride breath test was performed in 52 patients after PPPD to assess postoperative exocrine pancreatic function. A value of percent ¹³CO₂ cumulative dose at 7 h (%CD-7h) of less than 5% was considered diagnostic of exocrine pancreatic insufficiency. Pre- and postoperative pancreatic parenchymal thicknesses were calculated using computed tomography (CT) scans, and compared by means of receiver operating characteristic (ROC) analysis.
Thirty-four (65.4%) of 52 patients were found to have exocrine pancreatic insufficiency based on the breath test. With ROC analysis for identification of exocrine pancreatic insufficiency, the areas under the ROC curve for the postoperative pancreatic parenchymal thickness were higher than those for the preoperative pancreatic parenchymal thickness (0.904 and 0.702, respectively, P = 0.009). When the cut-off value of the postoperative pancreatic parenchymal thickness was set at 13.0 mm, the sensitivity and specificity for identifying exocrine pancreatic insufficiency were 88.2% and 88.9%, respectively.
Reduced postoperative pancreatic parenchymal thickness is a reliable indicator of exocrine pancreatic insufficiency after PPPD.
Usefulness of a 13C-labeled mixed triglyceride breath test for assessing pancreatic exocrine function after pancreatic surgery
2009, Surgery
Citation Excerpt :
The patients fasted for 7 hours, and they returned to their normal diet after 7 hours. Enrichment of 13CO2/12CO2 in breath was measured by infrared spectrometry using an Otsuka Ubit-IR 300 (Otuka Electronics), and results were expressed as values (referring to the international standard Pee Dee Belemnite), as described previously.16,17 Results were expressed as parts per thousand excess of δ13CO2 (Δ13CO2).
Although the fecal elastase-1 test is a satisfactory pancreatic exocrine function test, breath tests that use stable isotopes have been developed recently as alternatives. We evaluated the usefulness of a ¹³C-labeled mixed triglyceride breath test for assessing pancreatic exocrine function after pancreatic surgery.
The breath test and the fecal elastase-1 test were performed on 7 healthy volunteers, 10 patients with chronic pancreatitis, and 95 patients after pancreatic surgery. The breath test was analyzed with isotope ratio mass spectrometry and the cumulative recovery of ¹³CO₂ at 7 hours (% dose ¹³C cum 7h) was calculated. The fecal elastase-1 concentration was determined immunoenzymatically.
Both the fecal elastase-1 concentration and the % dose ¹³C cum 7h of chronic pancreatitis patients and pancreatic resection patients were less than those of healthy volunteers. In all subjects, % dose ¹³C cum 7h correlated with the fecal elastase-1 concentration (n = 112, R² = 0.14, P < .01). Accuracy rates for clinical symptoms, including clinical steatorrhea, for the fecal test and the breath test were 62 and 88%, respectively.
The ¹³C-labeled mixed triglyceride breath test might be more useful than the fecal elastase-1 test for evaluating pancreatic exocrine function after pancreatic resection.
Reformulated 17O correction of mass spectrometric stable isotope measurements in carbon dioxide and a critical appraisal of historic 'absolute' carbon and oxygen isotope ratios
2008, Geochimica et Cosmochimica Acta
Mass-spectrometric stable isotope measurements of CO₂ use molecular ion currents at mass-to-charge ratios m/z 44, 45 and 46 to derive the elemental isotope ratios n(¹³C)/n(¹²C) and n(¹⁸O)/n(¹⁶O), abbreviated ¹³C/¹²C and ¹⁸O/¹⁶O, relative to a reference. The ion currents have to be corrected for the contribution of ¹⁷O-bearing isotopologues, the so-called ‘¹⁷O correction’. The magnitude of this correction depends on the calibrated isotope ratios of the reference. Isotope ratio calibrations are difficult and are therefore a matter of debate. Here, I provide a comprehensive evaluation of the existing ¹³C/¹²C (¹³R), ¹⁷O/¹⁶O (¹⁷R) and ¹⁸O/¹⁶O (¹⁸R) calibrations of the reference material Vienna Standard Mean Ocean Water (VSMOW) and CO₂ generated from the reference material Vienna Pee Dee Belemnite (VPDB) by reaction with 100% H₃PO₄ at 25 °C (VPDB-CO₂). I find $^{17} R_{VSMOW} / 10^{- 6} = {382.7}_{- 2.1}^{+ 1.7}$ , ¹⁸R_VSMOW/10⁻⁶ = 2005.20 ± 0.45, $^{13} R_{VPDB- {CO}_{2}} / 10^{- 6} =$ 11124 ± 45, $^{17} R_{VPDB- {CO}_{2}} / 10^{- 6} = {391.1}_{- 2.1}^{+ 1.7}$ and $^{18} R_{VPDB- {CO}_{2}} / 10^{- 6} = 2088.37 \pm 0.90$ . I also rephrase the calculation scheme for the ¹⁷O correction completely in terms of relative isotope ratio differences (δ values). This reveals that only ratios of isotope ratios (namely, ¹⁷R/¹³R and ¹³R¹⁷R/¹⁸R) are required for the ¹⁷O correction. These can be, and have been, measured on conventional stable isotope mass spectrometers. I then show that the remaining error for these ratios of isotope ratios can lead to significant uncertainty in the derived relative ¹³C/¹²C difference, but not for¹⁸O/¹⁶O. Even though inter-laboratory differences can be corrected for by a common ‘ratio assumption set’ and/or normalisation, the ultimate accuracy of the ¹⁷O correction is hereby limited. Errors of similar magnitude can be introduced by the assumed mass-dependent relationship between ¹⁷O/¹⁶O and ¹⁸O/¹⁶O isotope ratios. For highest accuracy in the ¹³C/¹²C ratio, independent triple oxygen isotope measurements are required. Finally, I propose an experiment that allows direct measurement of ¹³R¹⁷R/¹⁸R.

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International Journal of Mass Spectrometry and Ion Physics

Abstract

References (14)

Physica

Physica

Geochim. Cosmochim. Acta

Meddel. Grønl.

Cited by (145)

Remnant pancreatic parenchymal volume predicts postoperative pancreatic exocrine insufficiency after pancreatectomy

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Reduced pancreatic parenchymal thickness indicates exocrine pancreatic insufficiency after pancreatoduodenectomy

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Reformulated <sup>17</sup>O correction of mass spectrometric stable isotope measurements in carbon dioxide and a critical appraisal of historic 'absolute' carbon and oxygen isotope ratios