Li Xiao-chuan, Yu Chen, Sun Wei-kang, Liu Gang-yi, Jia Jing-ying, Wang Yi-ping
Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Acta Pharmacol Sin. 2004 Nov;25(11):1402-7.
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.
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.
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.
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.
建立一种用于丹参素镁B（MLB）药代动力学研究的特异性液相色谱 - 串联质谱（LC-MS/MS）方法，并研究比格犬静脉注射MLB后的药代动力学。
每只比格犬随机静脉注射3、6和12mg/kg的MLB。采用特异性液相色谱 - 串联质谱（LC-MS/MS）分析法测定血清药物浓度。通过Drug and Statistics 1.0程序计算药代动力学参数。
MLB的校准曲线在16 - 4096μg/L范围内呈线性，相关系数>0.999。分析的日内和日间精密度（CV）<10%，准确度范围为90%至113%。静脉注射3、6和12mg/kg剂量的MLB后，MLB的C(0)值分别估计为24、47和107mg/L。静脉注射时AUC随剂量增加而增加，平均AUC(0-t)值分别为109.3、247.9和582.4mg·min·L(-1)。MLB从中央室快速分布和消除，3、6、12mg/kg剂量的MLB平均T(1/2α)值分别为2.2、2.7和2.9分钟，平均T(1/2β)值分别为43、42和42分钟。
该LC-MS/MS方法对于MLB的药代动力学研究快速、灵敏且特异。MLB在比格犬体内的动力学过程最适合二室模型。静脉注射时，C(0)和AUC的药代动力学参数在剂量间具有良好的线性关系，且MLB在比格犬体内分布和消除迅速。
