Quantitative analysis by liquid chromatography–tandem mass spectrometry of glycidamide using the cob(I)alamin trapping method: Validation and application to in vitro metabolism of acrylamide

Motwani, Hitesh V.; Törnqvist, Margareta

doi:10.1016/j.chroma.2011.05.008

Cited by 13 publications

(9 citation statements)

References 36 publications

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“…LOQs for AA and GA were reported as 0.5 µg/mL for the analysed matrices. Motwani and Törnqvist (2011) used cob(I)alamin, (Cbl(I)) for trapping of GA. The trapping of GA by Cbl(I) results in the formation of an alkylcobalamin (GA-Cbl) that was used for quantitative analysis of the epoxide.…”

Section: Biological Matricesmentioning

confidence: 99%

Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

342

170

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EFSA was asked to deliver a scientific opinion on acrylamide (AA) in food. AA has widespread uses as an industrial chemical. It is also formed when certain foods are prepared at temperatures above 120 °C and low moisture, especially in foods containing asparagine and reducing sugars. The CONTAM Panel evaluated 43 419 analytical results from food commodities. AA was found at the highest levels in solid coffee substitutes and coffee, and in potato fried products. Mean and 95th percentile dietary AA exposures across surveys and age groups were estimated at 0.4 to 1.9 µg/kg body weight (b.w.) per day and 0.6 to 3.4 µg/kg b.w. per day, respectively. The main contributor to total dietary exposure was generally the category 'Potato fried products (except potato crisps and snacks)'. Preferences in home-cooking can have a substantial impact on human dietary AA exposure. Upon oral intake, AA is absorbed from the gastrointestinal tract and distributed to all organs. AA is extensively metabolised, mostly by conjugation with glutathione but also by epoxidation to glycidamide (GA). Formation of GA is considered to represent the route underlying the genotoxicity and carcinogenicity of AA. Neurotoxicity, adverse effects on male reproduction, developmental toxicity and carcinogenicity were identified as possible critical endpoints for AA toxicity from experimental animal studies. The data from human studies were inadequate for dose-response assessment. The CONTAM Panel selected BMDL 10 values of 0.43 mg/kg b.w. per day for peripheral neuropathy in rats and of 0.17 mg/kg b.w. per day for neoplastic effects in mice. The Panel concluded that the current levels of dietary exposure to AA are not of concern with respect to non-neoplastic effects. However, although the epidemiological associations have not demonstrated AA to be a human carcinogen, the margins of exposure (MOEs) indicate a concern for neoplastic effects based on animal evidence. © European Food SUMMARYFollowing a request from the European Commission, the Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on acrylamide (AA) in food. The Panel developed the draft scientific opinion which underwent a public consultation from 1 July 2014 to 15 September 2014. The comments received and how they were taken into account when finalising the scientific opinion were published in an EFSA Technical Report (EFSA, 2015).AA is a low molecular weight, highly water soluble, organic compound. It is used inter alia as an industrial chemical and in the production of polyacrylamides. Heightened concerns about exposure to AA arose in 2002 when it was discovered that it forms when certain foods are prepared at temperatures usually above 120 °C and low moisture. It forms, at least in part, due to a Maillard reaction between certain amino acids, such as asparagine, and reducing sugars. However, several other pathways and precursors have also been proposed to contribute to AA formation. AA forms in numerous baked or fried carbohydrate-rich f...

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Section: Biological Matricesmentioning

confidence: 99%

Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

342

170

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“…We previously validated the cob(I)alamin trapping method for analyzing epoxides (Haglund et al, 2006;Motwani and Törnqvist, 2011), and we applied the method for enzyme kinetic measurements, leading to good reproducibility and high yields in terms of trapping epoxides with cob(I)alamin (Motwani et al, 2009). The same conditions were used in the present study, yielding an analytical epoxide recovery from liver S9 N 90% and an LOQ (limit of quantitation) of 1 μM (Haglund et al, 2006;Motwani et al, 2009).…”

Section: A Quantification Methods For Bd Epoxides In In Vitro Metabolismmentioning

confidence: 89%

In vivo doses of butadiene epoxides as estimated from in vitro enzyme kinetics by using cob(I)alamin and measured hemoglobin adducts: An inter-species extrapolation approach

Motwani

Törnqvist

2014

Toxicology and Applied Pharmacology

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“…2 ), which was characterized by LC-MS/MS (Supplementary information Notes 3 – 4 ). Earlier, the cobalamin method has been validated for analysis of GA from S9 matrix, where it was shown that the calibration curve was linear over a GA concentration from 200 μM down to 0.01 μM with coefficient of variation in the range 1.68–16.7% 8 .

Figure 2 Scheme showing metabolism of acrylamide (AA) and formation of corresponding adducts.…”

Section: Resultsmentioning

confidence: 99%

“…GA, is formed by oxidative metabolic transformation of AA by cytochrome P450 (P450) 2E1 (Fig. 2 ) 8 – 10 . Both AA and GA undergo glutathione conjugation, and GA can be hydrolyzed by epoxide hydrolase.…”

Section: Introductionmentioning

confidence: 99%

“…1 ). For accurate measurements of an electrophilic compound we have earlier developed a method where the electrophile is trapped with the reduced form of vitamin B 12 , cob(I)alamin, which results in formation of an alkylcobalamin, a stable derivative form of the electrophilic species 8 , 19 , 20 . This so called cobalamin-adduct method was employed in the present study for measuring the metabolic formation of GA from AA, and to follow disappearance of the epoxide in an in vitro metabolic system.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Parallelogram based approach for in vivo dose estimation of genotoxic metabolites in humans with relevance to reduction of animal experiments

Motwani

Frostne

Törnqvist

2017

Sci Rep

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When employing metabolism studies of genotoxic compounds/metabolites and cancer tests for risk estimation, low exposure doses in humans are roughly extrapolated from high exposure doses in animals. An improvement is to measure the in vivo dose, i.e. area under concentration-time curve (AUC), of the causative genotoxic agent. In the present work, we propose and evaluate a parallelogram based approach for estimation of the AUC of genotoxic metabolites that incorporates in vitro metabolic data and existing knowledge from published in vivo data on hemoglobin (Hb) adduct levels, using glycidamide (GA) as a case study compound that is the genotoxic metabolite of acrylamide (AA). The estimated value of AUC of GA per AUC of AA from the parallelogram approach vs. that from Hb adduct levels measured in vivo were in good agreement; 0.087 vs. 0.23 in human and 1.4 vs. 0.53 in rat, respectively. The described parallelogram approach is simple, and can be useful to provide an approximate estimation of the AUC of metabolites in humans at low exposure levels for which sensitive methods for analyzing the metabolites are not available, as well as aid in reduction of animal experiments for metabolism studies that are to be used for cancer risk assessment.

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Quantitative analysis by liquid chromatography–tandem mass spectrometry of glycidamide using the cob(I)alamin trapping method: Validation and application to in vitro metabolism of acrylamide

Cited by 13 publications

References 36 publications

Scientific Opinion on acrylamide in food

Scientific Opinion on acrylamide in food

In vivo doses of butadiene epoxides as estimated from in vitro enzyme kinetics by using cob(I)alamin and measured hemoglobin adducts: An inter-species extrapolation approach

Parallelogram based approach for in vivo dose estimation of genotoxic metabolites in humans with relevance to reduction of animal experiments

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