High‐performance liquid chromatography analysis of curcumin in rat plasma: application to pharmacokinetics of polymeric micellar formulation of curcumin

Abstract A simple, rapid and reliable high‐performance liquid chromatographic (HPLC) method was developed and validated for the determination of curcumin in rat plasma. Plasma was precipitated with acetonitrile after addition of the internal standard (IS), 4‐hydroxybenzophenone. Separation was achieved on a Waters µBondapak™ C 18 column (3.9 × 300 mm, 5 µm) using acetonitrile (55%) and citric buffer, pH 3.0 (45%) as the mobile phase (flow rate = 1.0 mL/min). The UV detection wavelength was 300 and 428 nm for IS and curcumin, respectively. The extraction efficiencies were 97.08, 95.69 and 94.90% for 50, 200 and 1000 ng/mL of curcumin in rat plasma, respectively. The calibration curve was linear over the range 0.02–1 µg/mL with a correlation coefficient of r 2 > 0.999. The intra‐ and inter‐day coefficients of variation were less than 13%, and mean intra‐ and inter‐day errors were less than ±6% at 50, 200 and 1000 ng/mL of curcumin. This assay was successfully applied to the pharmacokinetic studies of both solubilized curcumin and its polymeric micellar formulation in rats. It was found that polymeric micelles increased the half‐life of curcumin 162‐fold that of solubilized curcumin and increased the volume of distribution (Vd ss ) by 70‐fold. Copyright © 2007 John Wiley & Sons, Ltd.