Measurement of intact sulfate and glucuronide phytoestrogen conjugates in human urine using isotope dilution liquid chromatography-tandem mass spectrometry with [13C3]isoflavone internal standards

Clarke, Don; Lloyd, Antony S.; Botting, Nigel P.; Oldfield, Mark F.; Needs, Paul W.; Wiseman, Helen

doi:10.1016/s0003-2697(02)00275-0

Cited by 101 publications

(76 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have shown that the main metabolites of isoflavone are 7-glucuronides followed by 4Ј-glucuronides and that there are also small proportions of sulfate esters (Doerge et al, 2000;Clarke et al, 2002). The aim of this study was to directly measure the isoflavone metabolites simultaneously, without any sample treatment process affecting the ratios of glycosides and their aglycones and conjugates using an HPLC-UV-DAD method combined with solid-phase extraction.…”

Section: Discussionmentioning

confidence: 99%

“…The resulting estimates based on the enzymatically released aglycones do not provide detailed information on the type of conjugates or on the conjugation position(s) on the flavone skeleton for conjugated compounds circulating in plasma. Intact phytoestrogen sulfates and glucuronides in human urine have been measured using an isotope dilution LC-MS method (Clarke et al, 2002), but there have been no similar reports for human plasma.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Plasma Profiling of Intact Isoflavone Metabolites by High-Performance Liquid Chromatography and Mass Spectrometric Identification of Flavone Glycosides Daidzin and Genistin in Human Plasma after Administration of Kinako

Hosoda¹,

Furuta²,

Yokokawa³

et al. 2008

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:The roles of isoflavones in the prevention of several hormonedependent cancers and osteoporosis are of great interest. Despite many pharmacokinetics studies of the isoflavones, the actual types of conjugates circulating in the body and the position(s) of conjugation sites on the flavone skeleton are still uncertain because, in general, conjugated compounds in biological fluids have been evaluated by measuring the free aglycones obtained after selective enzymatic hydrolysis. Using an high-performance (HPLC)-UV-diode-array detector (DAD) method combined with solid-phase extraction, we have obtained HPLC profiles of isoflavone glycosides [daidzin (Din) and genistin (Gin)] and of intact isoflavone metabolites in human plasma: daidzein, genistein, daizein-7-glucuronide, daidzein-4-glucuronide, genistein-7-glucuronide, genistein-4-glucuronide, daidzein-7-sulfate, daidzein-4-sulfate, genistein-7-sulfate, and genistein-4-sulfate. We investigated the plasma profile of intact isoflavone metabolites in plasma obtained 1 to-7 h after orally administration of 50 g of kinako (baked soybean powder) to two healthy volunteers. The results of DAD analysis indicated that the main isoflavone metabolite peaks were identified on the HPLC chromatogram. Furthermore, the intact glycosides Din and Gin were detected in 1-h plasma samples by their positive electrospray ionization mass spectra, demonstrating that the glycosides Din and Gin can be absorbed from the gut.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Plasma Profiling of Intact Isoflavone Metabolites by High-Performance Liquid Chromatography and Mass Spectrometric Identification of Flavone Glycosides Daidzin and Genistin in Human Plasma after Administration of Kinako

Hosoda¹,

Furuta²,

Yokokawa³

et al. 2008

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…For example, studies with quercetin have shown that various factors influence the amount absorbed, including the plant source and the type and linkage position of sugar(s) (Hollman et al, 1997(Hollman et al, , 1999Erlund et al, 2000;Graefe et al, 2001). Further, recent studies have shown that quercetin (and other flavonoids and isoflavones) are present in plasma and urine as a mixture of conjugated forms (methylated/glucuronidated/sulphated) Clark et al, 2002). Therefore, in order to understand mechanisms and perform meaningful in vitro studies concerning potential health effects of flavonoids, it is critical to know how much is absorbed, what concentrations are relevant in vivo and the structures of the metabolites.…”

Section: Introductionmentioning

confidence: 99%

Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans

et al. 2004

View full text Add to dashboard Cite

Objective: To determine the absorption, excretion and metabolism of kaempferol in humans. Design: A pharmacokinetic study of kaempferol from endive over 24 h. Subjects: Four healthy males and four healthy females. Results: Kaempferol, from a relatively low dose (9 mg), was absorbed from endive with a mean maximum plasma concentration of 0.1 mM, at a time of 5.8 h, indicating absorption from the distal section of the small intestine and/or the colon. Although a 7.5-fold interindividual variation between the highest and lowest maximum plasma concentration was observed, most individuals showed remarkably consistent pharmacokinetic profiles. This contrasts with profiles for other flavonoids that are absorbed predominantly from the large intestine (eg rutin). An average of 1.9% of the kaempferol dose was excreted in 24 h. Most subjects also showed an early absorption peak, probably corresponding to kaempferol-3-glucoside, present at a level of 14% in the endive. Kaempferol-3-glucuronide was the major compound detected in plasma and urine. Quercetin was not detected in plasma or urine indicating a lack of phase I hydroxylation of kaempferol. Conclusions: Kaempferol is absorbed more efficiently than quercetin in humans even at low oral doses. The predominant form in plasma is a 3-glucuronide conjugate, and interindividual variation in absorption and excretion is low, suggesting that urinary kaempferol could be used as a biomarker for exposure. Sponsorship: Biotechnology and Biological Sciences Research council for core strategic funding and the University of Leeds for a departmental fellowship (AJD).

show abstract

“…In the present study, we examined transport of nine quercetin and isoflavone metabolites found in vivo in A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 16 glucuronides are the main metabolites in humans [10], OAT3 may contribute to the urinary excretion of isoflavones by mediating the uptake of glucuronide conjugates from blood into proximal tubules. Hence, OAT3-mediated transport could be one factor limiting the systemic availability of isoflavones.…”

Section: Discussionmentioning

confidence: 99%

“…Quercetin is metabolized into quercetin-3-O-glucuronide, 3′-methylquercetin-3-O-glucuronide and quercetin-3′-O-sulfate following consumption of onions [9]. After soy ingestion, soy isoflavones such as daidzein and genistein are present in the circulation predominantly as their 7-O-glucuronide and 4′-O-glucuronide, and sulfates were minor metabolites [10]. Concentrations of these metabolites in human plasma is typically low after intake of 50 mg aglycone equivalent and it rarely exceeds 10 μM even at much higher ingested doses [11].…”

Section: Introductionmentioning

confidence: 99%

Flavonoid conjugates interact with organic anion transporters (OATs) and attenuate cytotoxicity of adefovir mediated by organic anion transporter 1 (OAT1/SLC22A6)

Wong

Botting

Orfila

et al. 2011

Biochemical Pharmacology

View full text Add to dashboard Cite

. Flavonoid conjugates interact with organic anion transporters (OATs) and attenuate cytotoxicity of adefovir mediated by organic anion transporter 1 (OAT1/SLC22A6). Biochemical Pharmacology, Elsevier, 2011, 81 (7) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 of 37A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 may be a mechanism of food-drug interaction via inhibition of renal uptake.

show abstract

Measurement of intact sulfate and glucuronide phytoestrogen conjugates in human urine using isotope dilution liquid chromatography-tandem mass spectrometry with [13C3]isoflavone internal standards

Cited by 101 publications

References 21 publications

Plasma Profiling of Intact Isoflavone Metabolites by High-Performance Liquid Chromatography and Mass Spectrometric Identification of Flavone Glycosides Daidzin and Genistin in Human Plasma after Administration of Kinako

Plasma Profiling of Intact Isoflavone Metabolites by High-Performance Liquid Chromatography and Mass Spectrometric Identification of Flavone Glycosides Daidzin and Genistin in Human Plasma after Administration of Kinako

Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans

Flavonoid conjugates interact with organic anion transporters (OATs) and attenuate cytotoxicity of adefovir mediated by organic anion transporter 1 (OAT1/SLC22A6)

Contact Info

Product

Resources

About