大鼠体内米托蒽醌的血药浓度测定及药动学研究
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篇名: 大鼠体内米托蒽醌的血药浓度测定及药动学研究
TITLE:
摘要: 目的:建立测定大鼠体内米托蒽醌血药浓度的方法,研究米托蒽醌在大鼠体内的药动学。方法:取SD大鼠6只,尾静脉注射米托蒽醌5 mg/kg,分别于给药前和给药后5、10、20、40、60、120、240、480、720 min取尾静脉血0.3 mL,置于肝素化EP 管中,离心分离血浆,加入硅胶充分研磨混匀后,再加入含0.5 mol/L盐酸的甲醇溶液沉淀蛋白,研磨混匀,离心取上清液,氮气吹干后加流动相复溶。采用高效液相色谱法测定米托蒽醌的血药浓度,色谱柱为ZORBAX SB-C18,流动相为20 mmoL/L乙酸铵水溶液(用稀盐酸调pH至2.0)-甲醇(65 ∶ 35,V/V),流速为1.0 mL/min,检测波长为244 nm,柱温为30 ℃,进样量为20 μL,应用DAS 3.0软件计算药动学参数。结果:米托蒽醌检测质量浓度的线性范围为200~10 000 μg/L(r=0.999 6,n=6),定量下限为200 μg/L,检测限为150 μg/L;日内、日间精密度和稳定性试验的RSD均<8.0%(n分别为5、3、6);提取回收率为(85.64±3.93)%~(92.31±1.68)%(n=3);准确度试验中的回收率为(93.58±1.42)%~(113.92±2.74)%(n=6)。米托蒽醌在大鼠体内的药动学参数AUC0-720 min为(5 247.1±474.6) μg·h/L,t1/2z为(24.88±6.94) h,CLZ为(0.46±0.09) L/(h·kg),Vz为(11.07±2.64) L/kg。结论:该方法提取回收率高、重复性好,适用于米托蒽醌血药浓度的测定和药动学研究。
ABSTRACT: OBJECTIVE: To extablish the method for blood concentration determination of mitoxantrone in rats, and to study the pharamokinetics of mitoxantrone in rats. METHODS: Totally 6 SD rats were collected and given mitoxantrone 5 mg/kg via tail vein. The blood samples 0.3 mL were collected before medication and 5, 10, 20, 40, 60, 120, 240, 480, 720 min after medication. Blood samples were placed in heparinized EP tube, and the plasma was centrifuged and separated. After adding silica gel, the plasma were ground and mixed well, then added into methanol solution containing 0.5 mol/L hydrochloric acid to precipitate protein. After grinding and mixing, the supernatant was centrifuged and dried with nitrogen and then dissolved with mobile phase. HPLC method was adopted to determine the plasma concentration of mitoxantrone. The determination was performed on ZORBAX SB-C18 column with mobile phase consisted of 20 mmol/L ammonium acetate (pH adjusted to 2.0 with hydrochloric acid)-methanol (65 ∶ 35, V/V) at the flow rate of 1.0 mL/min. The detection wavelength was set at 244 nm, and column temperature was 30 ℃. The sample size was 20 μL. Pharmacokinetic parameters were calculated with DAS 3.0 software. RESULTS: The linear range of mitoxantrone were 200-10 000 μg/L (r=0.999 6, n=6). The lower limit of quantitation was 200   μg/L, and the limit of detection was 150 μg/L, respectively. RSDs of intra-day and inter-day precision and stability were all lower than 8.0% (n=5, 3, 6, respectively). The extraction recoveries were (85.64±3.93)%-(92.31±1.68)% (n=3). The recoveries of accuracy test were (93.58±1.42)%-(113.92±2.74)% (n=3). The pharmacokinetic parameters of mitoxantrone were as follows as AUC0-720 min was (5 247.1±474.6.0) μg·h/L; t1 /2z was (24.88±6.94) h; CLZ was (0.46±0.09) L/(h·kg); Vz was (11.07±2.64) L/kg. CONCLUSIONS: The method has recovery and good repeatability, and is suitable for the determination of blood concentration of mitoxantrone and its pharmacokinetic research.
期刊: 2019年第30卷第7期
作者: 荀桂洲,傅慧敏,胡敏,张全,叶静,张绍兰
AUTHORS: XUN Guizhou,FU Huimin,HU Min,ZHANG Quan,YE Jing,ZHANG Shaolan
关键字: 米托蒽醌;血药浓度测定;药动学;大鼠
KEYWORDS: Mitoxantrone; Blood concentration determination; Pharmacokinetics; Rat
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