ABSTRACT
Objective: To compare the differences in pharmacokinetic behavior of six ingredients in Qikui Sustained-release Tablets in rabbit plasma. Qikui Granules was taken as reference. Methods: Diazepam was used as internal standard. LC-MS/MS detection methods of astragaloside, hyperin, isoquercitrin, rutin, morroniside, and loganin in rabbit plasma were established, and pharmacokinetic parameters of six components were calculated. Results: Six active ingredients’ equation of linear regressions were: astragaloside Y = 1.0 × 10-4 X - 0.009 9 (r = 0.999 7), morroniside Y = 1.0 × 10-4 X + 0.038 7 (r = 0.999 4), loganin Y = 3.0 × 10-5 X + 0.008 7 (r = 0.999 3), hyperin Y = 1.0 × 10-3 X - 0.016 1 (r = 0.999 0), rutin Y = 5.0 × 10-4 X - 0.011 5 (r = 0.999 4), isoquercitrin Y = 1.7 × 10-3X - 0.307 5(r = 0.999 2). Intra-day and inter-day precision and accuracy and recovery rate were up to the mustard. After Qikui Sustained-release Tablets and Qikui Granules being given by gavege, the maximal concentration (Cmax) of morroniside, loganin, astragaloside, rutin, hyperin, and isoquerctirin in Qikui Granules were (1.333 ± 0.051), (1.238 ± 0.164), (0.83 ± 0.079), (0.127 ± 0.017),(0.444 ± 0.048), and (0.223 ± 0.048) mg/L, t1/2 were (3.848 ± 0.311), (3.822 ± 0.757), (4.982 ± 1.14), (3.73 ± 0.298), (4.732 ± 0.642), and (5.132 ± 0.901) h, respectively, AUC(0-t) were (3.069 ± 0.307), (2.891 ± 0.943), (2.079 ± 0.306), (0.313 ± 0.068), (1.087 ± 0.177), (0.496 ± 0.129) mg∙h/L, respectively, Cmax of morroniside, loganin, astragaloside, rutin, hyperin, and isoquerctirin in Qikui Sustained-release Tablets were (0.985 ± 0.13), (0.961 ± 0.175), (0.693 ± 0.101), (0.094 ± 0.012), (0.354 ± 0.045), (0.201 ± 0.037) mg/L, t1/2 were (4.691 ± 0.337), (5.62 ± 1.64), (6.408 ± 0.707), (4.103 ± 0.341), (6.048 ± 0.882), (5.803 ± 0.59) h, AUC(0-t) were (5.191 ± 1.046), (6.168 ± 1.25), (4.293 ± 0.823), (0.485 ± 0.103), (1.84 ± 0.432), (0.924 ± 0.19) mg∙h/L. Contrast with Qikui Granules, relative bioavailability of morroniside, loganin, astragaloside, rutin, hyperin, and isoquerctirin in Qikui Sustained-release Tablets were 169.1%, 213.3%, 206.5%, 156.0%, 169.3%, and 186.3%, respectively. Conclusion: Qikui Sustained-release Tablets can significantly improve the bioavailability of each active ingredient in rabbit.