液相色谱-质谱/质谱联用法比较苦参碱注射剂腹腔注射大鼠的药动学一致性

Comparison of pharmacokinetics of different matrine injections intraperitoneally injected to rats by LC-MS/MS method

目的:建立大鼠血浆中苦参碱浓度的LC-MS/MS测定法,研究苦参碱注射液、注射用苦参碱和苦参碱氯化钠注射液腹腔注射的体内药动学一致性。方法:SD大鼠30只,随机分为3组:苦参碱注射液组、注射用苦参碱组,苦参碱氯化钠注射液组,每组10只,分别单剂量(15 mg·m L-1)腹腔给药3个厂家苦参碱注射剂后,不同时间点眼内眦取血,LC-MS/MS法测定苦参碱血浆药物浓度,采用DAS 3.0软件计算药动学参数,以药动学参数为评价指标,采用SPSS 17.0软件进行一致性比较分析。结果:腹腔注射15 mg·kg-1的苦参碱注射液、注射用苦参碱和苦参碱氯化钠注射液后AUC(0-t)分别为(10 166±2 426),(12 064±3 854)ng·m L-1和(9 963±3 159)ng·m L-1·h;AUC(0-∞)分别为(10 230±2 432),(12 158±3 910)ng·m L-1·h和(10 037±3 631)ng·m L-1·h;MRT(0-t)分别为(1.91±0.41),(2.16±0.56)h和(2.15±0.45)h;MRT(0-∞)分别为(2.01±0.41),(2.26±0.5870)h和(2.37±0.68)h;t1/2分别为(2.26±0.89),(2.05±0.75)h和(2.63±2.44)h;Vd分别为(4.90±2.10),(4.82±1.32)L和(6.52±1.10)L;CL分别为(1.53±0.32),(1.35±0.42)L·h-1·kg-1和(1.63±0.41)L·h-1·kg-1;Cmax分别为(5 246±1 187),(5 160±1 517)ng·m L-1和(4 680±1 088)ng·m L-1。结论:苦参碱注射液、注射用苦参碱和苦参碱氯化钠注射液3个厂家药品腹腔给药后药动学参数AUC、MRT、t1/2、Vd、CL和Cmax均无统计学差异。

OBJECTIVE To establish a method for determination of matrine plasma concentration,and evaluate pharmacokinetics consistency of different matrine injections in vivo. METHODS Thirty healthy SD rats were enrolled and randomly divided into three groups to receive intraperitoneal administration of matrine injection,matrine for injection and matrine and sodium chloride injection at the dose of 15 mg·kg-1,respectively. Blood samples were immediately collected into heparinized tubes before injection and at different times after injection. Plasma sample concentrations were determined by a validated LC-MS/MS method. The pharmacokinetic parameters were calculated by DAS 3. 0 software. The pharmacokinetics parameters were analyzed by SPSS 17. 0. RESULTS The main pharmacokinetic parameters for matrine injection and matrine for injection after intraperitoneal administration at dose of 15 mg·kg-1 were as follows: AUC(0-t)(10 166 ± 2 426),(12 064 ± 3 854) ng·m L-1·h and(9 963 ± 3 159) ng·m L-1·h; AUC(0-∞)(10 230 ±2 432),(12 158 ± 3 910) ng·m L-1·h and(10 037 ± 3 631) ng·m L-1·h; MRT(0-t)(1. 91 ± 0. 41),(2. 16 ± 0. 56) h and(2. 15 ±0. 45) h; MRT(0-∞)(2. 01 ± 0. 41),(2. 26 ± 0. 587 0) h and(2. 37 ± 0. 68) h; t1/2(2. 26 ± 0. 89),(2. 05 ± 0. 75) h and(2. 63 ±2. 44) h; Vd(4. 90 ± 2. 10),(4. 82 ± 1. 32) L and(6. 52 ± 1. 10) L; CL(1. 53 ± 0. 32),(1. 35 ± 0. 42) L·h-1·kg-1 and(1. 63 ±0. 41) L·kg-1·h-1; Cmax(5 246 ± 1 187),(5 160 ± 1 517) ng·m L-1 and(4 680 ± 1 088) ng·m L-1. CONCLUSION No significant difference has been observed in AUC,MRT,t1/2,Vd,CL or Cmaxvalue of matrine between different manufactures.