摘要:
AIM: To develop a specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the pharmacokinetic study of magnesium lithospermate B (MLB), and study the pharmacokinetics of MLB after iv administration in beagle dogs.. METHODS: Each beagle dog was iv administered MLB 3, 6, and 12 mg/kg random. The serum drug concentration was determined by specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays. The pharmacokinetic parameters were calculated by Drug and Statistics version 1.0 program.RESULTS: The calibration curve for MLB was linear over a range of 16-4096 μg/L with coefficients of correlation>0.999. The intra- and inter-day precisions (CV) of analysis were <10 %, and accuracy ranged from 90 % to 113%. After iv administration of MLB at the doses of 3, 6, and 12 mg/kg, the Co values for MLB were estimated to be of 24, 47, and 107 mg/L, respectively. The AUC increased with the increasing doses for iv administration, and the mean AUC0-t values were 109.3,247.9, and 582.4 mg.min.L-1, respectively. MLB was distributed and eliminated quickly from central compartment, the mean T1/2α values for MLB at doses of 3, 6, 12 mg/kg were 2.2, 2.7, and 2.9 min,and the mean T1/2β values were 43, 42, and 42 min, respectively. CONCLUSION: This LC-MS/MS method is rapid, sensitive, and specific for the pharmacokinetic study of MLB. The kinetic process of MLB in beagle dogs in vivo was best fitted to a two-compartment model. For iv administration, the pharmacokinetic parameters of Co and AUC have good linearity among the doses, and MLB was distributed and eliminated quickly in beagle dogs.