Serum concentrations of rutoside metabolites after oral administration of a rutoside formulation to humans.

In the present study a highly specific and sensitive method by gas chromatography-mass spectrometry has been established for the determination of the blood levels of four metabolites of 5,7,3',4'-tetrahydroxyflavonol-3-rutinoside (rutoside, rutin), i.e. 3,4-dihydroxytoluene (DHT), 3-hydroxyphenylacetic acid (mPHAA), 3,4-dihydroxyphenylacetic acid (DHPAA), and 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid, HVA) after the oral administration of rutoside to healthy volunteers. By the established method the pharmacokinetics in the blood and the urinary excretion of those metabolites were investigated. Blood levels of DHT, mHPAA, DHPAA, and HVA started to increase at 4 to 8 h after the oral dosage of the rutoside formulation, Esberiven (further active ingredient: coumarin). At 8 to 12 h post-administration, blood levels reached a maximum level which was 2- to 3-fold the time 0 level. Blood levels decreased gradually afterwards and returned to the original level at 20 to 35 h. The sum of the four metabolites was at a maximum value at 8 h which then returned to the initial levels at 35 h yielding a half-life of 11 h. Total urinary excretion of metabolites was 50.5% of the dose in 48 h.