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1.
Anal Bioanal Chem ; 405(26): 8487-503, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23982107

RESUMO

Habitual consumption of medium amounts of coffee over the whole life-span is hypothesized to reduce the risk to develop diabetes type 2 (DM2) and Alzheimer's disease (AD). To identify putative bioactive coffee-derived metabolites, first, pooled urine from coffee drinkers and non-coffee drinkers were screened by UPLC-HDMS. After statistical data analysis, trigonelline, dimethylxanthines and monomethylxanthines, and ferulic acid conjugates were identified as the major metabolites found after coffee consumption. For quantitative analysis of these markers in body fluids, targeted methods based on stable-isotope dilution and UPLC-MS/MS were developed and applied to plasma samples from a coffee intervention study (n = 13 volunteers) who consumed a single cup of caffeinated coffee brew after a 10-day washout period. Chlorogenic acid-derived metabolites were found to be separated into two groups showing different pharmacokinetic properties. The first group comprised, e.g., ferulic acid and feruloyl sulfate and showed early appearance in the plasma (~1 h). The second group contained particularly chlorogenic acid metabolites formed by the intestinal microflora, appearing late and persisting in the plasma (>6 h). Trigonelline appeared early but persisted with calculated half-life times ~5 h. The plasma levels of caffeine metabolites significantly and progressively increased 2-4 h after coffee consumption and did not reach c max within the time frame of the study. The pharmacokinetic profiles suggest that particularly trigonelline, caffeine, its metabolites, as well as late appearing dihydroferulic acid, feruloylglycine and dihydroferulic acid sulfate formed from chlorogenic acid by the intestinal microflora accumulate in the plasma due to their long half-life times during habitual consumption of several cups of coffee distributed over the day. Since some of these metabolites have been reported to show antioxidant effects in vivo, antioxidant-response-element activating potential, and neuroprotective properties, respectively, some of these key metabolites might account for the inflammation- and DM2/AD risk reducing effects reported for habitual life time consumption of coffee.


Assuntos
Alcaloides/metabolismo , Cafeína/metabolismo , Ácido Clorogênico/metabolismo , Café/metabolismo , Ácidos Cumáricos/metabolismo , Xantinas/metabolismo , Adulto , Alcaloides/sangue , Alcaloides/urina , Cafeína/sangue , Cafeína/urina , Ácido Clorogênico/sangue , Ácido Clorogênico/urina , Ácidos Cumáricos/sangue , Ácidos Cumáricos/urina , Feminino , Humanos , Masculino , Espectrometria de Massas em Tandem , Xantinas/sangue , Xantinas/urina , Adulto Jovem
2.
Mol Nutr Food Res ; 55(11): 1613-23, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21618426

RESUMO

SCOPE: In order to validate the in vivo function of putatively healthy molecules in foods, human intervention studies are required. As the subject's compliance concerning intake or abstinence of a given food is considered mandatory to be monitored by biomarkers, the objective was to identify analytical markers for coffee consumption. METHODS AND RESULTS: Urine samples collected from coffee drinkers were compared with those of non-coffee drinkers using hydrophilic liquid interaction chromatography (HILIC)/time-of-flight mass spectrometry-based metabolite profiling. Two urinary molecules, found to be contributing most to the dissimilarities between both groups, were identified as N-methylpyridinium (NMP) and trigonelline and their suitability as coffee-specific biomarkers was validated by means of a coffee intervention study. After the volunteers (five females and four males) consumed a single dose of coffee, morning urine was collected for 10 days while staying abstinent from any coffee. HILIC-MS/MS-stable isotope dilution analysis (SIDA) revealed elevated urinary concentrations of trigonelline and NMP for up to 48 (p=0.001) and 72 h (p=0.002), respectively, after coffee consumption when compared with non-coffee drinkers. CONCLUSION: Analysis of urinary NMP allows to check for coffee consumption within a period of 3 days and is proposed as a dietary biomarker which might be used as an analytical probe to control compliance in human intervention studies on coffee.


Assuntos
Alcaloides/urina , Café , Compostos de Piridínio/urina , Adulto , Alcaloides/química , Biomarcadores/química , Biomarcadores/urina , Calibragem , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Estrutura Molecular , Cooperação do Paciente , Projetos Piloto , Compostos de Piridínio/química , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Fatores de Tempo , Adulto Jovem
3.
Anal Chem ; 82(4): 1486-97, 2010 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-20073472

RESUMO

The paper reports on the development of an accurate hydrophilic liquid interaction chromatography tandem mass spectrometry (HILIC-MS/MS) based stable isotope dilution analysis for the simultaneous quantitation of the food-derived bioactive pyridines trigonelline, nicotinic acid, nicotinamide, and N-methylpyridinium, as well as their key metabolites nicotinamide-N-oxide, N-methylnicotinamide, N-methyl-2-pyridone-5-carboxamide, N-methyl-4-pyridone-5-carboxamide, and N-methyl-2-pyridone-5-carboxylic acid in human plasma and urine. Precision of the stable isotope dilution analysis (SIDA) was 1.9% and 11.9% relative standard deviation (n = 6), and accuracy was between 92.4% and 113.0%. The lower limit of quantitation (LLOQ) was 50 fmol (10 pmol/mL) injected onto the column for all analytes with the exception of N-methyl-2-pyridone-5-carboxylic acid and N-methyl-2-pyridone-5-carboxamide, for which an LLOQ of 100 fmol (20 pmol/mL) was found. The method was applied to monitor the plasma appearance and urinary excretion and to determine pharmacokinetic parameters of the bioactive pyridines as well as their metabolites in a clinical human intervention study with healthy volunteers (six women, seven men) after oral administration of 350 mL of a standard coffee beverage. Trigonelline plasma levels increased from 160 nmol/L to maximum concentrations of 5479 (males) or 6547 nmol/L (females), and N-methylpyridinium plasma levels raised from virtually complete absence to maximum values of 777 (females) or 804 nmol/L (males) within 2-3 and 1-2 h after coffee consumption, respectively. The high plasma levels of N-methylpyridinium found after coffee consumption clearly demonstrate for the first time that this cation is entering the vascular system, which is the prerequisite for biological in vivo effects claimed for that compound. In contrast, the coffee intervention did not significantly influence the plasma concentrations of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-5-carboxamide, the major niacin metabolites. Within 8 h after coffee intervention, an urinary excretion of 57.4 +/- 6.9% of trigonelline and 69.1 +/- 6.2% of N-methylpyridinium was found for the male volunteers, whereas females excreted slightly less with 46.2 +/- 7.4% and 61.9 +/- 12.2% of these pyridines.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Café , Ingestão de Líquidos , Interações Hidrofóbicas e Hidrofílicas , Piridinas/metabolismo , Piridinas/farmacocinética , Espectrometria de Massas em Tandem/métodos , Administração Oral , Adulto , Alcaloides/sangue , Alcaloides/metabolismo , Alcaloides/farmacocinética , Alcaloides/urina , Cromatografia Líquida de Alta Pressão/normas , Café/metabolismo , Feminino , Humanos , Isótopos , Masculino , Piridinas/sangue , Piridinas/urina , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/normas , Adulto Jovem
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