Distribution of furanocoumarins in grapefruit juice fractions.
The reported effects of grapefruit (Citrus paradisi Macf.) juice on oral bioavailability of certain prescription drugs have led to the discovery of the inhibition by compounds in grapefruit of cytochrome P450 3A4 (CYP3A4) in the intestinal wall and liver. Recent evidence indicates that furanocoumarins related to bergamottin [5-[(3',7'-dimethyl-2',6'-octadienyl)oxy]psoralen] are primarily responsible for the grapefruit effect, yet the exact mechanisms and roles that specific compounds play in this effect are still uncertain. In the current experiments freshly extracted grapefruit juice was separated into four fractions, consisting of raw finished juice (approximately 5% fine pulp), centrifugal retentate (approximately 35% fine pulp), centrifuged supernatant (<1% pulp), and coarse finisher pulp. The relative concentrations of furanocoumarins in each of these grapefruit juice fractions were measured by HPLC-MS. These measurements showed that the centrifugal retentate had the highest furanocoumarin content, containing 892 ppm of bergamottin, 628 ppm of 6',7'-dihydroxybergamottin, 116 ppm of 6',7'-epoxybergamottin, 105 ppm of 7-geranyloxycoumarin, and approximately 467 ppm of furanocoumarin dimers. These high furanocoumarin concentrations make this fraction a useful starting material for preparative-scale isolations of these compounds. MS analysis of this furanocoumarin-enriched fraction provided evidence of additional furanocoumarins in grapefruit juice that remain to be fully characterized and evaluated for their roles in the grapefruit-drug interactions.
Manthey
John A
JA
Citrus and Subtropical Products Laboratory, Agricultural Research Service, US Department of Agriculture, Winter Haven, Florida 33881, USA. jmanthey@citrus.usda.gov
Buslig
Béla S
BS
D001628:Beverages / Q000032:analysis*; D002498:Centrifugation; D002851:Chromatography, High Pressure Liquid; D032083:Citrus paradisi / Q000737:chemistry*; D019281:Dimerization; D005638:Fruit / Q000737:chemistry*; D011564:Furocoumarins / Q000032:analysis*; D013058:Mass Spectrometry
D011564:Furocoumarins