An UPLC-MS/MS method for quantification of D-pinitol in rat plasma and its application to a pharmacokinetic and bioavailability study

D-pinitol could be a potential therapeutic agent for the treatment of diabetes mellitus (DM) type II. In this work, a sensitive and rapid ultra performance liquid chromatography coupled with tandem mass spectrometry method was firstly developed and validated for the determination and pharmacokinetic study of D-pinitol in rat plasma. D-pinitol and 5,7-dihydroxychromone (Internal Standard, IS) were completely separated on a BEH C18 column. The plasma samples were deproteinated with acetonitrile: ethanol (1:1). The MRM transitions for D-pinitol was m/z 179.125 -> 105.049, and for IS was m/z 195.085 -> 109.031. The method linearity ranges was 5-200 ng/mL. The precision, accuracy, recovery, matrix effect, stability under different conditions, were all within the required criteria. After intragastric (50 mg/kg) administration of D-pinitol to the rats, the maximum plasma concentration (C-max) was 77.8 +/- 19.5 ng/mL. The time to reach the maximum plasma concentration (T-max) was 2.2 +/- 0.98 h. Apparent distribution volume (V-z) was 1557.5 +/- 1329.1 L/kg and the plasma centration time curve (AUC(0-t)) was 1265.5 +/- 479.3 mu g/L*h. After intravenous (5.0 mg/kg) administration, V-z was 325.2 +/- 107.8 L/kg and AUC((0-t)) was 693.0 +/- 89.9 mu g/L*h. Our study indicated D-pinitol had a slow elimination phase and might be the high affinity binding to blood protein in vivo, which are helpful for its further drug development and clinical application.

Automated summary

This study developed a sensitive and rapid method for determining and studying the pharmacokinetics of D-pinitol in rat plasma, showing that D-pinitol has a slow elimination phase and a potential high affinity binding to blood protein in vivo.