An improved LC-MS/MS method for the determination of mangiferin in rat plasma and its application in nonlinear pharmacokinetics

A rapid and sensitive LC-MS/MS method was developed and validated for the determination of mangiferin in rat plasma. After simple protein precipitation of the plasma sample (100 mu L) with 120 mu L acetonitrile containing the internal standard rutin (500 ng/mL), the analytes were separated on a Zorbax SB-C-18 column (150 x 2.1 mm, 3.5 mu m) using an eluent of acetonitrile-0.05% formic acid in water (18:82, v/v), and then detected by electrospray ionization mass spectrometry in the negative multiple reaction monitoring mode with a chromatographic run time of 3.0 min. The method was sensitive, with a lower limit of quantification of 1 ng/mL and good linearity (r>0.998) over the range of 1-250 ng/mL. It was also specific, precise and accurate when it was used to measure mangiferin levels in plasma and to characterize the pharmacokinetic properties following oral administration of mangiferin at a single dose of 5, 15, 45 and 90 mg/kg in rats. In addition, the pharmacokinetics of mangiferin were found to be nonlinear over the above dose range, which provides insight into dose regimen design of this potent compound in new drug development.