液相色谱-串联质谱法测定大鼠血浆中靛蓝的浓度及药动学研究
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篇名: 液相色谱-串联质谱法测定大鼠血浆中靛蓝的浓度及药动学研究
TITLE:
摘要: 目的:建立测定大鼠血浆中靛蓝浓度的方法,研究靛蓝在大鼠体内的药动学特征。方法:将18只大鼠随机分为低、中、高剂量组,每组6只,分别ig 10、20、40 mg/kg的靛蓝溶液。分别于给药前和给药后0.083、0.25、0.5、0.75、1、2、4、6、8、10、12、16、24、48、72 h眼眶采全血0.3 mL,分离血浆,甲醇沉淀后采用液相色谱-串联质谱(LC-MS/MS)法测定靛蓝的血药浓度。色谱柱为Agilent Poroshell EC-C18,流动相为甲醇-5 mmol/L乙酸铵溶液(95 ∶ 5,V/V),流速为0.4 mL/min;以多反应监测(MRM)模式进行定量分析,用于监测的离子对(m/z)为263.1~218.8(靛蓝)和237.2~194.1(卡马西平,内标);采用DAS 3.0软件计算药动学参数。结果:靛蓝检测质量浓度的线性范围为0.5~100 ng/mL(r=0.999 9),日内、日间RSD均小于9%(n=5),低、中、高质量浓度的质控样品的基质效应分别为(98.25±3.71)%、(102.23±2.64)%、(102.29±3.79)%(n=5)。靛蓝在低、中、高剂量组大鼠体内的tmax分别为(8.6±1.1)、(9.2±0.8)、(9.5±0.8) h,cmax分别为(30.9±8.6)、(44.9±10.1)、(96.1±17.4) ng/mL,t1/2分别为(14.9±2.1)、(16.3±2.9)、(15.3±3.7) h,AUC0-72 h分别为(366.6±83.4)、(694.9±105.8)、(1 223.42±108.7) ng·h/mL。结论:本方法灵敏度高、特异性好,可用于大鼠血浆样品中靛蓝的含量测定;靛蓝在大鼠体内药动学特征符合非房室模型。
ABSTRACT: OBJECTIVE: To establish a method for the concentration determination of indigo in rats’ plasma, and study the pharmacokinetic characteristics in rats in vivo. METHODS: 18 rats were randomly divided into low-dose, medium-dose, high-dose groups, 6 in each group, which were intragastrically administrated 10, 20, 40 mg/kg of indigo solution. The sample blood 0.3 mL was taken from eye socket before administration and 0.083, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72 h after administration, separating the plasma, then LC-MS/MS was used to determine the plasma concentration of indigo after methanol precipitation. The column was Agilent Poroshell EC-C18 with mobile phase consisting of methanol-5 mmol/L ammonium acetate solution (95 ∶ 5,V/V) at a flow rate of 0.4 mL/min; multiple reaction monitoring was conducted for the quantitative analysis, with ion pair of 263.1-218.8 (indigo) and 237.2-194.1 (carbamazepine, internal standard). Pharmacokinetic parameters were calculated by DAS 3.0 software. RESULTS: The linear range of indigo was 0.5-100 ng/mL (r=0.999 9), intra-day and inter-day RSDs were lower than 9% (n=5); matrix effects of low, medium and high does quality control samples were (98.25±3.71)%, (102.23±2.64)%, (102.29±3.79)% (n=5). The pharmacokinetic parameters of indigo in low-dose, medium-dose, high-dose groups were tmax of (8.6±1.1), (9.2±0.8) and (9.5±0.8) h; cmax of (30.9±8.6), (44.9±10.1), (96.1±17.4) ng/mL; t1/2 of (14.9±2.1), (16.3±2.9), (15.3±3.7) h; AUC0-72 h of (366.6±83.4), (694.9±105.8), (1 223.42±108.7) ng·h/mL, respectively. CONCLUSIONS: The method shows high sensitivity, good specificity, and can be used for the content determination of indigo in plasma samples of rats. The pharmacokinetics of indigo in rats in vivo fits non-compartment model.
期刊: 2017年第28卷第7期
作者: 孔树佳,李砚文
AUTHORS: KONG Shujia,LI Yanwen
关键字: 靛蓝;液相色谱-串联质谱法;大鼠;血浆;药动学
KEYWORDS: Indigo; LC-MS/MS; Rats; Plasma; Pharmacokinetics
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