Stereoselective pharmacokinetics of dyphylline in rats
Objective To establish a novel chiral HPLC method to separate the enantiomers of dyphylline for the first time,and then successfully apply it to the stereoselective pharmacokinetic study in rats after intragastric administration of dyphylline racemate.Methods The chromatographic column was Chiralpak IG,acetonitrile-water(60:40,V/V)was used as the mobile phase,and the enantiomers of dyphylline were completely separated in less than 8 min at the optimal conditions.Six male SD rats were administrated by intragastric administration with racemic dyphylline.Plasma samples were treated with the protein precipitation method.The concentrations of dyphylline enantiomers in plasma were determined by LC-MS/MS method.Multiple reaction monitoring(MRM)scanning in positive ion mode was performed by electrospray ion source triple quadrupole mass spectrometry.Results The linear range of the single enantiomer of dyphylline in plasma was50.0-2 000.0 ng·mL-1,and the lower limit of quantitation was 50.0 ng·mL-1.The accuracy of the method ranged from-14.21％to 6.83％,the intra-day and inter-day precision(RSD)were less than 14.97％,and the recovery rate was from 104.19％to 110.20％.Pharmacokinetic parameters Tmax,t1/2 and Cmaxshowed no significant difference in stereoselectivity,CLz/F and AUC0-t showed significant difference(*P<0.05),AUC0-∞ showed extremely significant difference(**P<0.01).Conclusion The chiral HPLC method can be used to study the stereoselective pharmacokinetics of dyphylline in rats,and its pharmacokinetic process is stereoselective.
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