Oral Pharmacokinetic Comparison of Different Genistein Tablets in Beagle Dogs

An accurate and sensitive analytical method has been developed for the quantification of genistein in dog plasma using high-perform-ance liquid chromatography/tandem mass spectrometry. Genistein and diclofenac (internal standard) were extracted from the plasma sample using methyl tert-butyl ether and then separated on an Agilent Zorbax C18 column using a gradient mobile phase. The de-tector was a Q-trap mass spectrometer with an electrospray ioniza-tion interface operating in the multiple reaction monitoring mode. The assay was linear over the concentration range of 0.10–500 ng/ mL with a lower limit of quantification of 0.10 ng/mL. The method was shown to be reproducible and reliable, with inter-day and intra-day accuracy and precision within +15%. The method was successfully applied to a pharmacokinetic comparison of immediate and extended release tablets in beagle dogs after oral administra-tion. Immediate release tablets showed rapid genistein absorption, with mean peak concentration of 726+ 199 ng/mL reached at 0.2+ 0.0 h. However, the absorption of genistein was considerably slower and more sustainable for extended release tablets. The rela-tive bioavailability of the extended release tablet over the immedi-ate release formulation was estimated to be 134+ 47 % based on the AUCInf values from non-compartmental analysis