Tissue distribution study of mangiferin after intragastric administration of mangiferin monomer, Rhizoma Anemarrhenae, and Rhizoma Anemarrhenae-Phellodendron decoctions in normal or type 2 diabetic rats by LC-MS/MS.

A simple, accurate, and reliable liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for the determination of mangiferin in rat plasma and tissue homogenates using rutin as an internal standard (IS). Chromatographic separation was achieved on a Shiseido CAPCELL PAK C18 column (150 × 2.0 mm, 5 μm) using a gradient elution of 1% acetic acid in water and methanol at a flow rate of 300 μL·min−1. Quantification was performed on an API 4000+ triple-quadrupole mass spectrometer equipped with a turbo electrospray ionization (ESI) source in positive ion multiple reaction monitoring (MRM) mode. Selected ion monitoring transitions of 423.1 → 273.1 and 611.4 → 303.3 were chosen to quantify mangiferin and IS. Biological samples were pretreated via protein precipitation with acetonitrile-acetic acid. The standard calibration curves were above the ranges of 2 to 500 ng·mL−1 and 5 to 2000 ng·mL−1 for tissues, and 1 to 600 ng·mL−1 for plasma. All calibration curves for tissue and plasma samples showed good linearity (r ≥ 0.9974) over the concentration ranges. Intra- and inter-day precisions were <14.0%, and accuracy ranged from 97.2% to 111.7%. The established method was successfully applied on mangiferin tissue distribution following the intragastric administration of mangiferin, Rhizoma Anemarrhenae (A. Rhizoma) decoction, or Rhizoma Anemarrhenae-Phellodendron (herb pair, HP) decoction under healthy or diabetic conditions. Mangiferin was detected from all the tested tissues (except for brain) after monomer administration, and the concentrations were lower compared with the decoction groups. Distributions in the HP group were lower than those in the A. Rhizoma group, but mangiferin content in pancreas was obviously higher than in other tissues and in the A. Rhizoma group. Compared with healthy rats, mangiferin distributions in pancreas and intestine were lower in diabetic rats administered with the same dose of the herb pair, but still higher than those in other tissues. In addition, distributions in liver, spleen, lung, kidney, stomach, and plasma were higher than those in the normal group.