Production and certification of BOTS-1: bovine muscle-certified reference material for incurred veterinary drug residues.

A freeze-dried bovine muscle-certified reference material (CRM), known as BOTS-1 (DOI: https://doi.org/10.4224/crm.2018.bots-1 ), containing incurred residues of commonly used veterinary drugs was produced and certified for the mass fraction of eight veterinary drug residues. Value assignment was carried out using liquid chromatography tandem mass spectrometry (LC-MS/MS) methods in conjunction with isotope dilution and standard addition approaches involving stable isotope internal standards. Data from the National Research Council of Canada (NRC), Canadian Food Inspection Agency (CFIA), United States Department of Agriculture (USDA), and the Federal Office of Consumer Protection and Food Safety in Germany (BVL) were used for value assignment. Results for two drug residues were also obtained through an international inter-laboratory comparison CCQM-K141/P178 organized under the auspices of the International Bureau of Weights and Measures (BIPM). Quantitative NMR (1H-qNMR) was used to characterize primary standards of all veterinary drugs certified. The certified mass fractions of the veterinary drug residues were 490 ± 100 µg/kg for chlorpromazine, 44 ± 4.4 µg/kg for ciprofloxacin, 3.3 ± 1.4 µg/kg for clenbuterol, 9.5 ± 0.8 µg/kg for dexamethasone, 57 ± 4.8 µg/kg for enrofloxacin, 3.0 ± 0.4 µg/kg for meloxicam, 12.4 ± 1.2 µg/kg for ractopamine, and 2290 ± 120 µg/kg for sulfadiazine with expanded uncertainties quoted (95% confidence) which include the effects due to between-bottle inhomogeneity, instability during long-term storage and transportation, and characterization.

Isotopic measurements of carbon dioxide: the role of measurement science and standards.

Isotopic measurements provide valuable information about the origin of greenhouse gases - as carbon dioxide levels increase, there is a corresponding shift towards lighter isotopic composition similar to that of fossil fuels. Detecting such isotopic shifts, however, requires extremely precise measurements, which must also be globally reproducible in order to make reliable policy decisions. This feature article outlines the collective search for the ideal standard for carbon isotope measurements since the 1950s. This tragicomedy of errors, if you wish, has strengthened the reliability of today's measurements and has taken us from fictional oceans, to toilet seat marbles, and complex mathematical conventions that separate data from reliable results.

Comparison of Carbon Isotope Ratio Measurement of the Vanillin Methoxy Group by GC-IRMS and 13C-qNMR.

Site-specific carbon isotope ratio measurements by quantitative 13C NMR (13C-qNMR), Orbitrap-MS, and GC-IRMS offer a new dimension to conventional bulk carbon isotope ratio measurements used in food provenance, forensics, and a number of other applications. While the site-specific measurements of carbon isotope ratios in vanillin by 13C-qNMR or Orbitrap-MS are powerful new tools in food analysis, there are a limited number of studies regarding the validity of these measurement results. Here we present carbon site-specific measurements of vanillin by GC-IRMS and 13C-qNMR for methoxy carbon. Carbon isotope delta (δ13C) values obtained by these different measurement approaches demonstrate remarkable agreement; in five vanillin samples whose bulk δ13C values ranged from -31‰ to -26‰, their δ13C values of the methoxy carbon ranged from -62.4‰ to -30.6‰, yet the difference between the results of the two analytical approaches was within ±0.6‰. While the GC-IRMS approach afforded up to 9-fold lower uncertainties and required 100-fold less sample compared to the 13C-qNMR, the 13C-qNMR is able to assign δ13C values to all carbon atoms in the molecule, not just the cleavable methoxy group.

Preparation of 18O-labelled azaspiracids for accurate quantitation using liquid chromatography-mass spectrometry.

Azaspiracids (AZAs) are a group of polyether marine algal toxins known to accumulate in shellfish, posing a risk to human health and the seafood industry. Analysis of AZAs is typically performed using LC-MS, which can suffer from matrix effects that significantly impact the accuracy of measurement results. While the use of isotopic internal standards is an effective approach to correct for these effects, isotopically labelled standards for AZAs are not currently available. In this study, 18O-labelled AZA1, AZA2, and AZA3 were prepared by reaction with H218O under acidic conditions, and the reaction kinetics and sites of incorporation were studied using LC-HRMS/MS aided by mathematical analysis of their isotope patterns. Analysis of the isotopic incorporation in AZA1 and AZA3 indicated the presence of four exchangeable oxygen atoms. Excessive isomerization occurred during preparation of 18O-labelled AZA2, suggesting a role for the 8-methyl group in the thermodynamic stability of AZAs. Neutralized mixtures of 18O-labelled AZA1 and AZA3 were found to maintain their isotopic and isomeric integrities when stored at -20 °C and were used to develop an isotope-dilution LC-MS method which was applied to reference materials of shellfish matrices containing AZAs, demonstrating high accuracy and excellent reproducibility. Preparation of isotopically labelled compounds using the isotopic exchange method, combined with the kinetic analysis, offers a feasible way to obtain isotopically labelled internal standards for a wide variety of biomolecules to support reliable quantitation.

Characterization of vanillin carbon isotope delta reference materials.

Stable carbon isotope ratio measurements are used to investigate the provenance of vanillin. In this study, a variety of commercial vanillin samples and vanilla products were analyzed to provide a frame of reference for the variability of carbon isotope delta values in various vanillin samples, with the results ranging from -20.6 to -36.7‰ relative to the Vienna Peedee Belemnite (VPDB). We present information on the development of two synthetic vanillin reference materials, VANA-1 and VANB-1, prepared in 0.75 g units in glass vials, to be used for the calibration of carbon isotope delta measurements of vanillin and other easily combustible organic materials. Characterization of 40 vials each of VANA-1 and VANB-1 was performed by three laboratories over several measurement sequences. The certified carbon isotope delta values are -31.30 ± 0.06‰ (VANA-1) and -25.85 ± 0.05‰ (VANB-1). These uncertainties, for the 95% confidence level, include considerations for measurement uncertainty, coherence of the reference materials used for calibration, batch homogeneity, and stability during storage and transportation. The results are traceable to the VPDB through a set of nine reference materials (IAEA-CH-6, USGS65, IAEA-600, NBS22, USGS61, IAEA-603, IAEA-610, IAEA-611, and IAEA-612). For up to date certified values, users should refer to doi.org/10.4224/crm.2022.vana-1 and doi.org/10.4224/crm.2022.vanb-1.

Site-specific carbon isotope measurements of vanillin reference materials by nuclear magnetic resonance spectrometry.

Vanillin, one of the world's most popular flavor used in food and pharmaceutical industries, is extracted from vanilla beans or obtained (bio)-synthetically. The price of natural vanillin is considerably higher than that of its synthetic alternative which leads increasingly to counterfeit vanillin. Here, we describe the workflow of combining carbon isotope ratio combustion mass spectrometry with quantitative carbon nuclear magnetic resonance spectrometry (13C-qNMR) to obtain carbon isotope measurements traceable to the Vienna Peedee Belemnite (VPDB) with 0.7‰ combined standard uncertainty (or expanded uncertainty of 1.4‰ at 95% confidence level). We perform these measurements on qualified Bruker 400 MHz instruments to certify site-specific carbon isotope delta values in two vanillin materials, VANA-1 and VANB-1, believed to be the first intramolecular isotopic certified reference material (CRMs).

Production and stability of Oxygen-18 labeled Caribbean ciguatoxins and gambierones.

Ciguatoxins (CTXs) and gambierones are ladder-shaped polyethers associated with ciguatera poisoning and Gambierdiscus spp. Several of these compounds contain carbonyl or hemiketal groups, which have the potential to exchange with 18O-labeled water under acidic conditions. The effects of solvent composition and acid on the rate of exchange and on the stability of the labels at various pH values were assessed to optimize the incorporation of 18O into Caribbean ciguatoxin-1 and -2 (C-CTX1/2), gambierone, and 44-methylgambierone. LC-HRMS results showed that 18O-labeling occurred at the hydroxy group of the hemiketal at C-56 in C-CTX1/2, and at the hydroxy group of the hemiketal at C-4 and the ketone at C-40 in gambierones. Labeling occurred very rapidly (complete in <30 min) for C-CTX1/2, and more slowly (complete in ca. 16 h) for both gambierones. Labeled C-CTX1/2 was reduced with sodium borohydride to produce 18O-labeled C-CTX3/4. The incorporated 18O labels in the gambierones and C-CTXs were retained in aqueous solvent mixtures under neutral conditions in a short-term stability study, demonstrating that these 18O-labeled toxins have the potential to be used in isotope dilution and metabolism studies.

Thermal stability of cannabinoids in dried cannabis: a kinetic study.

This study was undertaken to quantitatively explore the effect of temperature on the degradation of cannabinoids in dried cannabis flower. A total of 14 cannabinoids were monitored using liquid chromatography and tandem mass spectrometry in temperature environments from - 20 to + 40 ∘C lasting up to 1 year. We find that a network of first-order degradation reactions is well-suited to model the observed changes for all cannabinoids. While most studies focus on high-temperature effects on the cannabinoids, this study provides high-precision quantitative assessment of room temperature kinetics with applications to shelf-life predictions and age estimates of cannabis products.

Discontinuity in the Realization of the Vienna Peedee Belemnite Carbon Isotope Ratio Scale.

By convention, carbon isotope ratios are expressed relative to VPDB defined by the calcite standard NBS19 in the 1980s. [See T. Coplen, Pure Appl. Chem. 1994, 66, 273-276.] To improve the realization of the VPDB scale, a second fixed point (lithium carbonate, LSVEC) was introduced in 2006 [T. Coplen et al. Anal. Chem. 2006, 78, 2439-2441], which is now known to be isotopically unstable. [Assonov, S. Rapid Commun. Mass Spectrom., 2018, 32, 827-830.] With the high-quality reference materials made available in 2020, it is now possible to realize the VPDB scale with high confidence. [Assonov, S. et al. Rapid Commun. Mass Spectrom., 2020, 34, e8867; Assonov, S. Rapid Commun. Mass Spectrom. 2021, 35, e9014; Qi, H. et al. Rapid Commun. Mass Spectrosc. 2021, 35, e9006.] Here, we report the analysis of 25 reference materials using isotope ratio combustion mass spectrometry, show the discontinuity between the values measured against the new IAEA reference materials and the values currently assigned to these reference materials on the VPDB2006, and provide a link bringing these materials onto the new VPDB2020.

Determination of the Isotopic Composition of Zirconium Using MC-ICPMS and a Regression Model for Mass Bias Correction.

Measurements of zirconium isotopes provide insights into the formation of planetary bodies, dating nuclear explosions, or maintenance of nuclear reactors. Although many comparative measurements for the isotopic composition of zirconium have been performed using mass spectrometry, there is a lack of zirconium isotopic reference materials and only a single calibrated measurement has been reported to date by total evaporation thermal ionization mass spectrometry (TE-TIMS). In this study, we report an independent measurement of full zirconium isotopic composition in a new zirconium isotopic reference material by multicollector inductively coupled plasma MS using the regression method and two independent certified isotopic reference materials, NIST SRM 984 Rb and NIST SRM 987 Sr. Our results agree well with the recent TE-TIMS measurements and suggest a revision of the standard atomic weight of zirconium.