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

ABSTRACT

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 microL) with 120 microL acetonitrile containing the internal standard rutin (500 ng/mL), the analytes were separated on a Zorbax SB-C18 column (150 x 2.1 mm, 3.5 microm) using an eluent of acetonitrile-0.05% formic acid in water (1882, 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.