title: Rapid Quantitation of Furanocoumarins and Flavonoids in Grapefruit Juice using Ultra-Performance Liquid Chromatography.
abstract: BACKGROUND
  Grapefruit juice can increase or decrease the systemic exposure of myriad oral medications, leading to untoward effects or reduced efficacy. Furanocoumarins in grapefruit juice have been established as inhibitors of cytochrome P450 3A (CYP3A)-mediated metabolism and P-glycoprotein (P-gp)-mediated efflux, while flavonoids have been implicated as inhibitors of organic anion transporting polypeptide (OATP)-mediated absorptive uptake in the intestine. The potential for drug interactions with a food product necessitates an understanding of the expected concentrations of a suite of structurally diverse and potentially bioactive compounds.
  
  
  OBJECTIVE
  Develop methods for the rapid quantitation of two furanocoumarins (bergamottin and 6',7'-dihydroxybergamottin) and four flavonoids (naringin, naringenin, narirutin and hesperidin) in five grapefruit juice products using ultra-performance liquid chromatography (UPLC).
  
  
  METHODS
  Grapefruit juice products were extracted with ethyl acetate; the concentrated extract was analysed by UPLC using acetonitrile:water gradients and a C18 -column. Analytes were detected using a photodiode array detector, set at 250 nm (furanocoumarins) and 310 nm (flavonoids). Intraday and interday precision and accuracy and limits of detection and quantitation were determined.
  
  
  RESULTS
  Rapid (< 5.0 min) UPLC methods were developed to measure the aforementioned furanocoumarins and flavonoids. R(2) values for the calibration curves of all analytes were >0.999. Considerable between-juice variation in the concentrations of these compounds was observed, and the quantities measured were in agreement with the concentrations published in HPLC studies.
  
  
  CONCLUSIONS
  These analytical methods provide an expedient means to quantitate key furanocoumarins and flavonoids in grapefruit juice and other foods used in dietary substance-drug interaction studies.
authors.affiliation: Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Patricia A. Sullivan Science Building, PO Box 26170, Greensboro, NC, 27402, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Vandermolen
authors.forename: Nadja B
authors.initials: NB
authors.lastname: Cech
authors.forename: Mary F
authors.initials: MF
authors.lastname: Paine
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Oberlies
mesh_terms: D001628:Beverages / Q000032:analysis*; D002853:Chromatography, Liquid / Q000379:methods*; D032083:Citrus paradisi / Q000737:chemistry*; D005419:Flavonoids / Q000032:analysis*; D011564:Furocoumarins / Q000032:analysis*; D016018:Least-Squares Analysis; D015203:Reproducibility of Results
chemical_list: D005419:Flavonoids; D011564:Furocoumarins
keywords: UPLC; flavonoid; furanocoumarin; grapefruit; quantitation