Context: 1 D is a novel derivative of curcumin and shows very promising antitumor activities in various cancer cell lines. Objective: To characterize its preclinical pharmacokinetic profiles, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of 1 D in rat plasma. Materials and methods: An aliquot of 50 mu L plasma sample was processed by protein precipitation with methanol. Chromatographic separation was accomplished on a Zorbax Eclipse Plus C-18 column (2.1 mm x 50 mm, 1.8 mu m) with a gradient elution system (water/0.1% formic acid and methanol). Detection was performed by multiple reaction monitoring (MRM) mode using electrospray ionization in the positive ion mode. The optimized fragmentation transition for 1 D was m/z 491.2 -> 361.2. Results: The method was linear over the concentration range of 5-1000 ng/mL. The intra- and inter-day precisions were less than 9.8% and the accuracy was within +/- 14.5%. The mean recovery of 1 D ranged from 102.5 to 105.9%. No matrix effects and significant sample loss during sample processing were observed. The validated method has been successfully applied to a pharmacokinetic study in rats after intravenous administration of 1 D. Non-compartmental pharmacokinetic parameters, including half-life (t(1/2)), apparent volume of distribution (V-z), clearance (CLz), and area under the concentration-time curve (AUC((0-t))) were 4.92 h, 46.56 L/kg, 6.33 L/h/kg, and 806.70 mu g/L/h, respectively. Discussion and conclusions: Results demonstrated that 1 D displayed favourable pharmacokinetic properties for further in vivo pharmacologic evaluation, which could be facilitated by the validated LC-MS/MS method.