Résumé
A high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the determination of mizoribine in human serum using thiamphenicol as internal standard (IS). The serum samples of mizoribine were precipitated with acetonitrile and separated by HPLC on a reversed phase C18 column with a mobile phase of 0.1% ammonium acetate water solution-methanol (47:53, v/v). Mizoribine and IS were detected in the multiple reaction monitoring mode with precursor/product ion transitions of m/z 258.2/126.0 and 354.1/185.2, respectively. The calibration curves were linear over the range of 0.02-2 microg mL(-1) for mizoribine. The limit of quantification (LOQ) was 0.02 microg mL(-1) with acceptable precision and accuracy. The validated method was successfully applied for the evaluation of a bioequivalence study on Chinese healthy volunteers. The main pharmacokinetics parameters after oral administration of 100 mg mizoribine test or reference formulation were as follows: Cmax (1.00 +/- 0.21), (1.00 +/- 0.22) microg mL(-1); AUC(0-infinity) (6.72 +/- 1.39), (6.48 +/- 1.44) microg h mL(-1); t1/2 (2.77 +/- 0.26), (2.66 +/- 0.29) h; tmax (2.95 +/- 0.78), (2.84 +/- 0.50) h.
Sujets)
Adulte , Humains , Mâle , Jeune adulte , Aire sous la courbe , Asiatiques , Chromatographie en phase liquide à haute performance , Méthodes , Intervalles de confiance , Antienzymes , Sang , Pharmacocinétique , Immunosuppresseurs , Sang , Pharmacocinétique , Ribonucléosides , Sang , Pharmacocinétique , Spectrométrie de masse ESI , Méthodes , Équivalence thérapeutiqueRésumé
To investigate the absorption mechanism of diammonium glycyrrhizinate (GL) for oral use in rat intestine as well as the effect of phospholipids on GL and its metabolite glycyrrhetic acid (GA), in situ single pass intestinal perfusion model and the rat single-pass intestinal perfusion with mesenteric cannulation model were used and the concentrations of GL and GA in perfusate and blood were determined by HPLC. The apparent permeability values (Papp) of GA with or without phospholipids are 7.98 and 5.73 cm x min(-1), respectively, whereas the permeability of GL had no significant statistical difference. The results showed that phospholipids can increase the absorption extent and speed of GA. This action can be used in the research and development of the new drugs of the glycyrrhiza.