Pharmacokinetics and liver distribution study of unbound curdione and curcumol in rats by microdialysis coupled with rapid resolution liquid chromatography (RRLC) and tandem mass spectrometry

•An in vivo microdialysis system was successfully established for simultaneous biological fluid sampling in the blood and liver of a rat.•RRLC–MS was utilized to achieve rapid resolution, high sensitivity and low analytical costs.•It is the first investigation on the simultaneous analysis of curdione and curcumol in biological fluids of rat.•The results provided a meaningful basis for better understanding of the intracorporal process of Rhizoma Curcumae. A sensitive, specific, convenient and endogenous interference-free microdialysis sampling method coupled with RRLC–MS was successfully developed and applied to the determination of protein-unbound curdione and curcumol in biological samples. Microdialysis probes were simultaneously inserted into the jugular vein toward heart and the median lobe near the center of liver of rats under anesthesia. The separation was accomplished on a Zorbax SB-C18 column (2.1mm×50mm, 1.8μm) with a gradient elution and chromatography was conducted with RRLC system. Analytes were detected by positive ion electrospray tandem mass spectrometry and quantified on the basis of extracted ion chromatography (EIC) peak area signal. The calibration curves were linear over the range of 3.3–213.2ng/mL for curdione and 8.1–519.2ng/mL for curcumol. All the validation data, such as accuracy, precision, stability and matrix effect were satisfactory and within the required limits. The validated method was successfully applied to the pharmacokinetic study of curdione and curcumol in rat blood and liver after oral administration of Rhizoma Curcumae extracts. The results could provide a meaningful basis for better understanding of the intracorporal process of Rhizoma Curcumae, which would be helpful for further study both in clinic and laboratory.