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Pharmacokinetics of magnesium lithospermate B after intravenous administration in beagle dogs.

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 i.v. 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 microg/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 i.v. administration of MLB at the doses of 3, 6, and 12 mg/kg, the C(0) 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 AUC(0-t) values were 109.3, 247.9, and 582.4 mg x min x L(-1), respectively. MLB was distributed and eliminated quickly from central compartment, the mean T(1/2alpha) values for MLB at doses of 3, 6, 12 mg/kg were 2.2, 2.7, and 2.9 min, and the mean T(1/2beta) 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 i.v. administration, the pharmacokinetic parameters of C(0) and AUC have good linearity among the doses, and MLB was distributed and eliminated quickly in beagle dogs.[1]

References

  1. Pharmacokinetics of magnesium lithospermate B after intravenous administration in beagle dogs. Li, X.C., Yu, C., Sun, W.K., Liu, G.Y., Jia, J.Y., Wang, Y.P. Acta Pharmacol. Sin. (2004) [Pubmed]
 
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