Application of Liquid Chromatography−Tandem Mass SpectrometryTo Determine Urinary Concentrations of Five Commonly Used Low-Calorie Sweeteners: A Novel Biomarker Approach for Assessing Recent Intakes?

Research output: Other contribution

Abstract

Although the use of low-calorie sweeteners (LCSs) is widespread, methods of assessing consumption within free-living populations have inherent limitations. Five commonly consumed LCSs, namely, acesulfame-K, saccharin, sucralose, cyclamate, and steviol glycosides, are excreted via the urine, and therefore a urinary biomarker approach may provide more objective LCS intake data. A LC-ESI-MS/MS method of simultaneously determining acesulfame-K, saccharin, sucralose, cyclamate, and the excretory metabolite of steviol glycosides, steviol glucuronide, in human urine was developed and validated. Linearity was observed over a concentration range of 10−1000 ng/mL with coefficients of determination ranging from 0.9969 to0.9997. Accuracy ranged from 92 to 104%, and intrabatch and interday precisions were within acceptable limits with %CV below 8% for all compounds. A double-blind, randomized crossover dose−response study was conducted to assess the usefulness of urinary LCS excretions (from both fasting spot and a full 24-h urine collection) for investigating recent intakes. Both modes ofsampling were useful for distinguishing between the three short-term intakes of acesulfame-K, saccharin, cyclamates, and steviol glycosides (p <0.001), whereas for sucralose, urinary concentrations were useful for distinguishing between low (0.1% ADI) and high doses (10% ADI) only (p <0.001). In summary, this biomarker approach may be useful for assessing intakes of fivecommonly consumed LCSs.
LanguageEnglish
TypeThe item being deposited is an original research paper describing the development and validation of an analytical method for the simultaneous analysis of five low-calorie sweeteners in urine as well as details on validation of urinary excretions as m...
Publication statusE-pub ahead of print - 16 May 2017

Fingerprint

trichlorosucrose
Sweetening Agents
Liquid Chromatography
Cyclamates
Saccharin
Biomarkers
Glycosides
Urine
Urine Specimen Collection
Glucuronides
Fasting
steviol
Population
acetosulfame

Keywords

  • low-calorie sweeteners
  • intense sweeteners
  • biomarkers
  • urinary biomarkers
  • exposure
  • food additives
  • human urine

Cite this

@misc{71c1ee6c015d4a76b41cc1052d1feb12,
title = "Application of Liquid Chromatography−Tandem Mass SpectrometryTo Determine Urinary Concentrations of Five Commonly Used Low-Calorie Sweeteners: A Novel Biomarker Approach for Assessing Recent Intakes?",
abstract = "Although the use of low-calorie sweeteners (LCSs) is widespread, methods of assessing consumption within free-living populations have inherent limitations. Five commonly consumed LCSs, namely, acesulfame-K, saccharin, sucralose, cyclamate, and steviol glycosides, are excreted via the urine, and therefore a urinary biomarker approach may provide more objective LCS intake data. A LC-ESI-MS/MS method of simultaneously determining acesulfame-K, saccharin, sucralose, cyclamate, and the excretory metabolite of steviol glycosides, steviol glucuronide, in human urine was developed and validated. Linearity was observed over a concentration range of 10−1000 ng/mL with coefficients of determination ranging from 0.9969 to0.9997. Accuracy ranged from 92 to 104{\%}, and intrabatch and interday precisions were within acceptable limits with {\%}CV below 8{\%} for all compounds. A double-blind, randomized crossover dose−response study was conducted to assess the usefulness of urinary LCS excretions (from both fasting spot and a full 24-h urine collection) for investigating recent intakes. Both modes ofsampling were useful for distinguishing between the three short-term intakes of acesulfame-K, saccharin, cyclamates, and steviol glycosides (p <0.001), whereas for sucralose, urinary concentrations were useful for distinguishing between low (0.1{\%} ADI) and high doses (10{\%} ADI) only (p <0.001). In summary, this biomarker approach may be useful for assessing intakes of fivecommonly consumed LCSs.",
keywords = "low-calorie sweeteners, intense sweeteners, biomarkers, urinary biomarkers, exposure, food additives, human urine",
author = "Caomhan Logue and Dowey, {Le Roy} and JJ Strain and Hans Verhagen and Stephen Mcclean and Alison Gallagher",
note = "Reference text: (1) Butland, B.; Jebb, S.; Kopelman, P.; McPherson, K.; Thomas, S.; Mardell, J.; Parry, V. Foresight, Tackling Obesities: Future Choices- Project Report, 2nd ed.; U.K. Government for Science, 2007. (2) Finucane, M. M.; Stevens, G. A.; Cowan, M. J.; Danaei, G.; Lin, J. K.; Paciorek, C. J.; Singh, G. M.; Gutierrez, H. R.; Lu, Y.; Bahalim, A. N.; Farzadfar, F.; Riley, L. M.; Ezzati, M. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 countryyears and 9.1 million participants. Lancet 2011, 377, 557−567. (3) Fryar, C. D.; Carroll, M. D.; Ogden, C. L. Prevalence of Overweight, Obesity, and Extreme Obesity among Adults: United States, 1960−1962 through 2011−2012 [online]; National Center for Health Statistics, Division of Health and Nutrition Examination Surveys, 2014; http://www.cdc.gov/nchs/data/hestat/obesity_adult_11_12/ obesity_adult_11_12.htm (accessed March 4, 2015). (4) World Health Organisation. Obesity and Overweight Fact sheet No. 311 [online]; WHO Media Centre, 2015; http://www.who.int/ mediacentre/factsheets/fs311/en/ (accessed May 15, 2015). (5) World Health Organisation. Guideline: Sugars intake for adults and children [online]; 2015; http://apps.who.int/iris/bitstream/ 10665/149782/1/9789241549028_eng.pdf (accessed Oct 2, 2016). (6) Scientific Advisory Committee on Nutrition (SACN) Carbohydrates and Health [online]; 2015; https://www.gov.uk/government/ uploads/system/uploads/attachment_data/file/445503/SACN_ Carbohydrates_and_Health.pdf (accessed Jan 11, 2016). (7) Grenby, T. H. Update on low-calorie sweeteners to benefit dental health. Int. Dent. J. 1991, 41, 217−224. (8) Rodgers, P. J.; Hognkamp, P. S.; de Graaf, C.; Higgs, S.; Lluch, A.; Ness, A. R.; Penfold, C.; Perry, R.; Putz, P.; Yeomans, M. R.; Mela, D. J. Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies. Int. J. Obes. 2016, 40, 387− 394. (9) Swithers, S. E. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol. Metab. 2013, 24, 431−441. (10) Imamura, F.; O’Connor, L.; Ye, Z.; Mursu, J.; Hayashino, Y.; Bhupathiraju, S. N.; Forouhi, N. G. Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. Br. J. Sports Med. 2016, 50, 496−504. (11) Romo-Romo, A.; Aguilar-Salinas, C. A.; Brito-Córdova, G.; Gómez D{\'i}az, R. A.; Valentin, D. V.; Almeda-Valdes, P. Effects of nonnutritive sweeteners on glucose metabolism and appetite regulating hormones: systematic review of observational prospective studies and clinical trials. PLoS One 2016, 11, e0161264. (12) Gardner, C.; Wylie-Rosett, J.; Gidding, S. S.; Steffen, L. M.; Johnson, R. K.; Reader, D.; Lichtenstein, A. H. Nonnutritive sweeteners: current use and health perspectives. Diabetes Care 2012, 35, 1798−1808. (13) Burke, M. V.; Small, D. M. Physiological mechanisms by which non-nutritive sweeteners may impact body weight and metabolism. Physiol. Behav. 2015, 152 (Part B), 381−388. (14) French Agency for Food, Environmental and Occupational Health and Safety (ANSES). Opinion on the assessment of the nutritional benefits and risks related to intense sweeteners. [online]; 2015; https://www.anses.fr/en/system/files/NUT2011sa0161RaEN. pdf (accessed Feb 23, 2015). (15) Lange, T.; Scheurer, M.; Brauch, H. J. Artificial sweeteners- a recently recognised class of emerging environmental contaminants: a review. Anal. Bioanal. Chem. 2012, 403, 2503−2518. (16) Bingham, S. A. Biomarkers in nutritional epidemiology. Public Health Nutr. 2002, 5, 821−827. (17) Landberg, R.; Aman, P.; Friberg, L. E.; Vessby, B.; Adlercreutz, H.; Kamal-Eldin, A. Dose-response of whole-grain biomarkers: alkylresorcinols in human plasma and their metabolites in urine in relation to intake. Am. J. Clin. Nutr. 2009, 89, 290−296. (18) Renwick, A. G. The metabolism of intense sweeteners. Xenobiotica 1986, 16 (10/11), 1057−1071. (19) Wilson, L. A.; Wilkinson, K.; Crews, H. M.; Davies, A. M.; Dick, C. S.; Dumsday, V. L. Urinary monitoring of saccharin and acesulfame- K as biomarkers of exposure to these additives. Food Addit. Contam. 1999, 16 (6), 227−238. (20) Roberts, A.; Renwick, A. G.; Sims, J.; Snodin, D. J. Sucralose metabolism and pharmacokinetics in man. Food Chem. Toxicol. 2000, 38 (Suppl. 2), S31−S41. (21) Geuns, J. M. C.; Buyse, J.; Vankeirsbilck, A.; Temme, E. H. M.; Compernolle, F.; Toppet, S. Identification of steviol glucuronide in human urine. J. Agric. Food Chem. 2006, 54, 2794−2798. (22) Logue, C.; Dowey, L.C.; Strain, J. J.; Verhagen, H.; Gallagher, A. M. The potential application of a biomarker approach to investigate low-calorie sweetener exposure. Proc. Nutr. Soc. 2016, 75 (2), 216− 225. (23) Jenab, M.; Slimani, N.; Bictash, M.; Ferrari, P.; Bingham, S. A. Biomarkers in nutritional epidemiology: applications, needs and new horizons. Hum. Genet. 2009, 125, 507−525. (24) Scheurer, M.; Brauch, H. J.; Lange, F. T. Analysis and occurrence of seven artificial sweeteners in German waste water and surface water and in soil aquifer treatment (SAT). Anal. Bioanal. Chem. 2009, 394 (6), 1585−1594. (25) Zygler, A.; Wasik, A.; Namiesnik, J. Analytical methodologies for determination of artificial sweeteners in foodstuffs. TrAC, Trends Anal. Chem. 2009, 28 (9), 1082−1102. (26) Ordonez, E. Y.; Quintana, J. B.; Rodil, R.; Cela, R. Determination of artificial sweeteners in water samples by solidphase extraction and liquid chromatography-tandem mass spectrometry. J. Chromatogr. A 2012, 1256, 197−205. (27) Ens, W.; Senner, F.; Gygax, B. Development, validation and application of a novel LC-MS/MS trace analysis method for the simultaneous quantification of seven iodinated X-ray contrast media and three artificial sweeteners in surface, ground, and drinking water. Anal. Bioanal. Chem. 2014, 406, 2789−2798. (28) Kuhnle, G. Nutritional biomarkers for objective dietary assessment. J. Sci. Food Agric. 2012, 92, 1145−1149. (29) Bingham, S.; Cummings, J. H. The use of 4-aminobenzoic acid as a marker to validate the completeness of 24 h urine collections in man. Clin. Sci. 1983, 64, 629−635. (30) Jakobsen, J.; Ovesen, L.; Fagt, S.; Pedersen, A. N. Paraaminobenzoic acid used as a marker for completeness of 24 h urine: Journal of Agricultural and Food Chemistry Article DOI: 10.1021/acs.jafc.7b00404 J. Agric. Food Chem. 2017, 65, 4516−4525 4524 assessment of control limits for a specific HPLC method. Eur. J. Clin. Nutr. 1997, 51, 514−519. (31) Agilent Technologies. Analysing Synthetic Sweeteners in Waste Water with Robust Sample Preparation. Application Note (Environmental) [online]; 2011; http://www.chem.agilent.com/Library/ applications/5990-8248EN.pdf (accessed March 23, 2013). (32) U.S. Food and Drug Administration (FDA). Guidance for Industry, Bioanalytical Method Validation, 2001. (33) Renwick, A. G. The intake of intense sweeteners − an update review. Food Addit. Contam. 2006, 23 (4), 327−338. (34) Yang, D. J.; Chen, B. Simultaneous determination of nonnutritive sweeteners in foods by HPLC/ESI-MS. J. Agric. Food Chem. 2009, 57, 3022−3027. (35) Christ, O.; Rupp, W. Human experiments with Acetosulfam- 14C. Pharmacokinetics after oral administration of 30 mg to three healthy male probands. 1976, Unpublished report. In Acesulfame Potassium. WHO Food Additives Series 28 [online]; http://www. inchem.org/documents/jecfa/jecmono/v28je13.htm (accessed June 3, 2015). (36) Ball, L. M.; Renwick, A. G.; Williams, A. G. The fate of [14C] saccharin in man, rat and rabbit and of 2-sulphamoyl[14C]benzoic acid in the rat. Xenobiotica 1977, 7, 189−203. (37) Sweatman, T. W.; Renwick, A. G.; Burgess, C. D. The pharmacokinetics of saccharin in man. Xenobiotica 1981, 11, 531−540. (38) Renwick, A. G.; Thompson, J. P.; O’Shaughnessy, M.; Walter, E. J. The metabolism of cyclamate to cyclohexylamine in humans during long-term administration. Toxicol. Appl. Pharmacol. 2004, 196, 367− 380. (39) Bopp, B. A.; Sonders, R. C.; Kesterson, J. W. Toxicological aspects of cyclamate and cyclohexylamine. Crit. Rev. Toxicol. 1986, 16 (3), 213−306. (40) Wheeler, A.; Boileau, A. C.; Winkler, P. C.; Compton, J. C.; Jiang, X.; Mandarino, D. A. Pharmacokinetics of rebaudioside A and stevioside after single oral doses in healthy men. Food Chem. Toxicol. 2008, 46, S54−S60. (41) Geuns, J. M. C.; Buyse, J.; Vankeirsbilck, A.; Temme, E. H. M. Metabolism of stevioside by healthy subjects. Exp. Biol. Med. 2007, 232, 164−173.",
year = "2017",
month = "5",
day = "16",
language = "English",
type = "Other",

}

Application of Liquid Chromatography−Tandem Mass SpectrometryTo Determine Urinary Concentrations of Five Commonly Used Low-Calorie Sweeteners: A Novel Biomarker Approach for Assessing Recent Intakes? / Logue, Caomhan; Dowey, Le Roy; Strain, JJ; Verhagen, Hans; Mcclean, Stephen; Gallagher, Alison.

2017, The item being deposited is an original research paper describing the development and validation of an analytical method for the simultaneous analysis of five low-calorie sweeteners in urine as well as details on validation of urinary excretions as m....

Research output: Other contribution

TY - GEN

T1 - Application of Liquid Chromatography−Tandem Mass SpectrometryTo Determine Urinary Concentrations of Five Commonly Used Low-Calorie Sweeteners: A Novel Biomarker Approach for Assessing Recent Intakes?

AU - Logue, Caomhan

AU - Dowey, Le Roy

AU - Strain, JJ

AU - Verhagen, Hans

AU - Mcclean, Stephen

AU - Gallagher, Alison

N1 - Reference text: (1) Butland, B.; Jebb, S.; Kopelman, P.; McPherson, K.; Thomas, S.; Mardell, J.; Parry, V. Foresight, Tackling Obesities: Future Choices- Project Report, 2nd ed.; U.K. Government for Science, 2007. (2) Finucane, M. M.; Stevens, G. A.; Cowan, M. J.; Danaei, G.; Lin, J. K.; Paciorek, C. J.; Singh, G. M.; Gutierrez, H. R.; Lu, Y.; Bahalim, A. N.; Farzadfar, F.; Riley, L. M.; Ezzati, M. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 countryyears and 9.1 million participants. Lancet 2011, 377, 557−567. (3) Fryar, C. D.; Carroll, M. D.; Ogden, C. L. Prevalence of Overweight, Obesity, and Extreme Obesity among Adults: United States, 1960−1962 through 2011−2012 [online]; National Center for Health Statistics, Division of Health and Nutrition Examination Surveys, 2014; http://www.cdc.gov/nchs/data/hestat/obesity_adult_11_12/ obesity_adult_11_12.htm (accessed March 4, 2015). (4) World Health Organisation. Obesity and Overweight Fact sheet No. 311 [online]; WHO Media Centre, 2015; http://www.who.int/ mediacentre/factsheets/fs311/en/ (accessed May 15, 2015). (5) World Health Organisation. Guideline: Sugars intake for adults and children [online]; 2015; http://apps.who.int/iris/bitstream/ 10665/149782/1/9789241549028_eng.pdf (accessed Oct 2, 2016). (6) Scientific Advisory Committee on Nutrition (SACN) Carbohydrates and Health [online]; 2015; https://www.gov.uk/government/ uploads/system/uploads/attachment_data/file/445503/SACN_ Carbohydrates_and_Health.pdf (accessed Jan 11, 2016). (7) Grenby, T. H. Update on low-calorie sweeteners to benefit dental health. Int. Dent. J. 1991, 41, 217−224. (8) Rodgers, P. J.; Hognkamp, P. S.; de Graaf, C.; Higgs, S.; Lluch, A.; Ness, A. R.; Penfold, C.; Perry, R.; Putz, P.; Yeomans, M. R.; Mela, D. J. Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies. Int. J. Obes. 2016, 40, 387− 394. (9) Swithers, S. E. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol. Metab. 2013, 24, 431−441. (10) Imamura, F.; O’Connor, L.; Ye, Z.; Mursu, J.; Hayashino, Y.; Bhupathiraju, S. N.; Forouhi, N. G. Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. Br. J. Sports Med. 2016, 50, 496−504. (11) Romo-Romo, A.; Aguilar-Salinas, C. A.; Brito-Córdova, G.; Gómez Díaz, R. A.; Valentin, D. V.; Almeda-Valdes, P. Effects of nonnutritive sweeteners on glucose metabolism and appetite regulating hormones: systematic review of observational prospective studies and clinical trials. PLoS One 2016, 11, e0161264. (12) Gardner, C.; Wylie-Rosett, J.; Gidding, S. S.; Steffen, L. M.; Johnson, R. K.; Reader, D.; Lichtenstein, A. H. Nonnutritive sweeteners: current use and health perspectives. Diabetes Care 2012, 35, 1798−1808. (13) Burke, M. V.; Small, D. M. Physiological mechanisms by which non-nutritive sweeteners may impact body weight and metabolism. Physiol. Behav. 2015, 152 (Part B), 381−388. (14) French Agency for Food, Environmental and Occupational Health and Safety (ANSES). Opinion on the assessment of the nutritional benefits and risks related to intense sweeteners. [online]; 2015; https://www.anses.fr/en/system/files/NUT2011sa0161RaEN. pdf (accessed Feb 23, 2015). (15) Lange, T.; Scheurer, M.; Brauch, H. J. Artificial sweeteners- a recently recognised class of emerging environmental contaminants: a review. Anal. Bioanal. Chem. 2012, 403, 2503−2518. (16) Bingham, S. A. Biomarkers in nutritional epidemiology. Public Health Nutr. 2002, 5, 821−827. (17) Landberg, R.; Aman, P.; Friberg, L. E.; Vessby, B.; Adlercreutz, H.; Kamal-Eldin, A. Dose-response of whole-grain biomarkers: alkylresorcinols in human plasma and their metabolites in urine in relation to intake. Am. J. Clin. Nutr. 2009, 89, 290−296. (18) Renwick, A. G. The metabolism of intense sweeteners. Xenobiotica 1986, 16 (10/11), 1057−1071. (19) Wilson, L. A.; Wilkinson, K.; Crews, H. M.; Davies, A. M.; Dick, C. S.; Dumsday, V. L. Urinary monitoring of saccharin and acesulfame- K as biomarkers of exposure to these additives. Food Addit. Contam. 1999, 16 (6), 227−238. (20) Roberts, A.; Renwick, A. G.; Sims, J.; Snodin, D. J. Sucralose metabolism and pharmacokinetics in man. Food Chem. Toxicol. 2000, 38 (Suppl. 2), S31−S41. (21) Geuns, J. M. C.; Buyse, J.; Vankeirsbilck, A.; Temme, E. H. M.; Compernolle, F.; Toppet, S. Identification of steviol glucuronide in human urine. J. Agric. Food Chem. 2006, 54, 2794−2798. (22) Logue, C.; Dowey, L.C.; Strain, J. J.; Verhagen, H.; Gallagher, A. M. The potential application of a biomarker approach to investigate low-calorie sweetener exposure. Proc. Nutr. Soc. 2016, 75 (2), 216− 225. (23) Jenab, M.; Slimani, N.; Bictash, M.; Ferrari, P.; Bingham, S. A. Biomarkers in nutritional epidemiology: applications, needs and new horizons. Hum. Genet. 2009, 125, 507−525. (24) Scheurer, M.; Brauch, H. J.; Lange, F. T. Analysis and occurrence of seven artificial sweeteners in German waste water and surface water and in soil aquifer treatment (SAT). Anal. Bioanal. Chem. 2009, 394 (6), 1585−1594. (25) Zygler, A.; Wasik, A.; Namiesnik, J. Analytical methodologies for determination of artificial sweeteners in foodstuffs. TrAC, Trends Anal. Chem. 2009, 28 (9), 1082−1102. (26) Ordonez, E. Y.; Quintana, J. B.; Rodil, R.; Cela, R. Determination of artificial sweeteners in water samples by solidphase extraction and liquid chromatography-tandem mass spectrometry. J. Chromatogr. A 2012, 1256, 197−205. (27) Ens, W.; Senner, F.; Gygax, B. Development, validation and application of a novel LC-MS/MS trace analysis method for the simultaneous quantification of seven iodinated X-ray contrast media and three artificial sweeteners in surface, ground, and drinking water. Anal. Bioanal. Chem. 2014, 406, 2789−2798. (28) Kuhnle, G. Nutritional biomarkers for objective dietary assessment. J. Sci. Food Agric. 2012, 92, 1145−1149. (29) Bingham, S.; Cummings, J. H. The use of 4-aminobenzoic acid as a marker to validate the completeness of 24 h urine collections in man. Clin. Sci. 1983, 64, 629−635. (30) Jakobsen, J.; Ovesen, L.; Fagt, S.; Pedersen, A. N. Paraaminobenzoic acid used as a marker for completeness of 24 h urine: Journal of Agricultural and Food Chemistry Article DOI: 10.1021/acs.jafc.7b00404 J. Agric. Food Chem. 2017, 65, 4516−4525 4524 assessment of control limits for a specific HPLC method. Eur. J. Clin. Nutr. 1997, 51, 514−519. (31) Agilent Technologies. Analysing Synthetic Sweeteners in Waste Water with Robust Sample Preparation. Application Note (Environmental) [online]; 2011; http://www.chem.agilent.com/Library/ applications/5990-8248EN.pdf (accessed March 23, 2013). (32) U.S. Food and Drug Administration (FDA). Guidance for Industry, Bioanalytical Method Validation, 2001. (33) Renwick, A. G. The intake of intense sweeteners − an update review. Food Addit. Contam. 2006, 23 (4), 327−338. (34) Yang, D. J.; Chen, B. Simultaneous determination of nonnutritive sweeteners in foods by HPLC/ESI-MS. J. Agric. Food Chem. 2009, 57, 3022−3027. (35) Christ, O.; Rupp, W. Human experiments with Acetosulfam- 14C. Pharmacokinetics after oral administration of 30 mg to three healthy male probands. 1976, Unpublished report. In Acesulfame Potassium. WHO Food Additives Series 28 [online]; http://www. inchem.org/documents/jecfa/jecmono/v28je13.htm (accessed June 3, 2015). (36) Ball, L. M.; Renwick, A. G.; Williams, A. G. The fate of [14C] saccharin in man, rat and rabbit and of 2-sulphamoyl[14C]benzoic acid in the rat. Xenobiotica 1977, 7, 189−203. (37) Sweatman, T. W.; Renwick, A. G.; Burgess, C. D. The pharmacokinetics of saccharin in man. Xenobiotica 1981, 11, 531−540. (38) Renwick, A. G.; Thompson, J. P.; O’Shaughnessy, M.; Walter, E. J. The metabolism of cyclamate to cyclohexylamine in humans during long-term administration. Toxicol. Appl. Pharmacol. 2004, 196, 367− 380. (39) Bopp, B. A.; Sonders, R. C.; Kesterson, J. W. Toxicological aspects of cyclamate and cyclohexylamine. Crit. Rev. Toxicol. 1986, 16 (3), 213−306. (40) Wheeler, A.; Boileau, A. C.; Winkler, P. C.; Compton, J. C.; Jiang, X.; Mandarino, D. A. Pharmacokinetics of rebaudioside A and stevioside after single oral doses in healthy men. Food Chem. Toxicol. 2008, 46, S54−S60. (41) Geuns, J. M. C.; Buyse, J.; Vankeirsbilck, A.; Temme, E. H. M. Metabolism of stevioside by healthy subjects. Exp. Biol. Med. 2007, 232, 164−173.

PY - 2017/5/16

Y1 - 2017/5/16

N2 - Although the use of low-calorie sweeteners (LCSs) is widespread, methods of assessing consumption within free-living populations have inherent limitations. Five commonly consumed LCSs, namely, acesulfame-K, saccharin, sucralose, cyclamate, and steviol glycosides, are excreted via the urine, and therefore a urinary biomarker approach may provide more objective LCS intake data. A LC-ESI-MS/MS method of simultaneously determining acesulfame-K, saccharin, sucralose, cyclamate, and the excretory metabolite of steviol glycosides, steviol glucuronide, in human urine was developed and validated. Linearity was observed over a concentration range of 10−1000 ng/mL with coefficients of determination ranging from 0.9969 to0.9997. Accuracy ranged from 92 to 104%, and intrabatch and interday precisions were within acceptable limits with %CV below 8% for all compounds. A double-blind, randomized crossover dose−response study was conducted to assess the usefulness of urinary LCS excretions (from both fasting spot and a full 24-h urine collection) for investigating recent intakes. Both modes ofsampling were useful for distinguishing between the three short-term intakes of acesulfame-K, saccharin, cyclamates, and steviol glycosides (p <0.001), whereas for sucralose, urinary concentrations were useful for distinguishing between low (0.1% ADI) and high doses (10% ADI) only (p <0.001). In summary, this biomarker approach may be useful for assessing intakes of fivecommonly consumed LCSs.

AB - Although the use of low-calorie sweeteners (LCSs) is widespread, methods of assessing consumption within free-living populations have inherent limitations. Five commonly consumed LCSs, namely, acesulfame-K, saccharin, sucralose, cyclamate, and steviol glycosides, are excreted via the urine, and therefore a urinary biomarker approach may provide more objective LCS intake data. A LC-ESI-MS/MS method of simultaneously determining acesulfame-K, saccharin, sucralose, cyclamate, and the excretory metabolite of steviol glycosides, steviol glucuronide, in human urine was developed and validated. Linearity was observed over a concentration range of 10−1000 ng/mL with coefficients of determination ranging from 0.9969 to0.9997. Accuracy ranged from 92 to 104%, and intrabatch and interday precisions were within acceptable limits with %CV below 8% for all compounds. A double-blind, randomized crossover dose−response study was conducted to assess the usefulness of urinary LCS excretions (from both fasting spot and a full 24-h urine collection) for investigating recent intakes. Both modes ofsampling were useful for distinguishing between the three short-term intakes of acesulfame-K, saccharin, cyclamates, and steviol glycosides (p <0.001), whereas for sucralose, urinary concentrations were useful for distinguishing between low (0.1% ADI) and high doses (10% ADI) only (p <0.001). In summary, this biomarker approach may be useful for assessing intakes of fivecommonly consumed LCSs.

KW - low-calorie sweeteners

KW - intense sweeteners

KW - biomarkers

KW - urinary biomarkers

KW - exposure

KW - food additives

KW - human urine

M3 - Other contribution

ER -