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Specific and sensitive ultra-high performance liquid chromatography-quadrupole time of flight-mass spectroscopy (UPLC-QTOF-MS) methods have been developed for the determination of curcuminoids and curcumin metabolites in human blood plasma. The UPLC-QTOF-MS method used a binary solvent delivery system and the chromatographic separation was performed on a C-18 (2.1 × 50 mm; 1.7 µm) column. Mass spectra were obtained on a Waters Xevo G2S Q-TOF mass spectrometer. The developed methods to characterize the pharmacokinetics of curcuminoids and curcumin metabolites in human blood plasma after an oral administration of bioavailable curcumin—Cureit™—were validated. It was found that the complete turmeric matrix enhances the concentration of tetrahydrocurcumin (THC), hexahydrocurcumin (HHC), octahydrocurcumin (OHC), curcumin-O-glucuronide (COG) and curcumin-O-sulfate (COS) in the blood plasma once the product is administrated.