Pharmacokinetics of oxymatrine and its metabolite in beagle dogs by LC-MS

Objective: To establish LC-MS method in the determination of oxymatrine and its metabolite in plasma and investigate their pharmacokinetics in beagle dogs. Method: Lichrospher C18 column (4.6 mm × 250 mm, 5 μm) was used as the analytical column maintained at 25°C. The mobile phase was consisted of 10 mmol·L^-1 CH₃COONH₄ and CH₃OH (25:75). Flow rate was 1mL·min^-1. Electrospray ionization (ESI) was carried out. The ESI ion source was set in positive ion polasity mode. The selective ion monitoring (SIM) was set at m/z 265.1 and 249.2. Result: The linearity ranged from 2 to 5 000 ng·mL^-1(r = 0.999 1). The detection of oxymatrine and its metabolite were 0.6 and 0.3 ng·mL ^-1. The RSD(%) within day and between day was less than 4.7%. The recovery of this method was more than 96.5%. The disposition was conformed to a two-compartment model. The T_1/2, T_max, C_max, MRT, AUC_0→24h of oxymatrine were (5.5 ± 1.58) h, (1.0 ± 0.30) h, (2 418.3 ± 970.78) ng·mL^-1, (3.2 ± 0.64) h, (5 797.4 ± 908.16) ng·mL^-1·h accordingly. The corresponding T_1/2, T_max, C _max, MRT, AUC_0→24h of matrine were (9.8 ± 2.77) h, (1.9 ± 1.09) h, (1 532.4 ± 494.86) ng·mL ^-1, (4.4 ± 1.97) h, (5 530.5 ± 1 042.65) ng·mL^-1·h. Conclusion: This assay was highly sensitive, rapid, simple and specific enough for determining concentrations of oxymatrine and its metabolite matrine in plasma of beagle dog.