孕三烯酮胶囊多次给药在巴马小型猪体内的药代动力学研究

发布时间：2018-06-25 01:47

  本文选题：孕三烯酮(三烯高诺酮) + 液相色谱-质谱联用　； 参考：《药物分析杂志》2017年07期

【摘要】：目的:建立快速灵敏的HPLC-MS/MS法测定巴马小型猪血浆中孕三烯酮的浓度,并研究孕三烯酮胶囊在巴马小型猪体内的药代动力学特征。方法:以巴马小型猪为实验动物,连续给药12周,每周给药2次,于给药后不同时间点采集血样。通过测定多次给药后小型猪血浆中孕三烯酮的浓度,计算其药代动力学参数。测定血浆样品以孕二烯酮为内标,经环己烷液液萃取后进行LC-MS/MS分析。色谱柱:Agilent ZORBAX Extend-C_(18)(2.1 mm×50 mm,5μm);流动相:水(含0.1%甲酸)-乙腈(含0.1%甲酸),梯度洗脱;流速:0.40 m L·min~(-1);进样量:20μL;柱温:35℃。质谱检测采用ESI正离子模式,扫描方式为多重反应监测(MRM)模式,选择检测离子反应对为m/z 309.2→241.1(孕三烯酮),m/z 311.2→109.1(孕二烯酮)。结果:孕三烯酮在0.1~10 ng·mL~(-1)浓度范围内线性良好(r=0.999 9),定量下限为0.1 ng·mL~(-1)。提取回收率均高于83.1%,日间、日内RSD均小于11.3%,专属性良好,在本实验涉及的条件下样品稳定。8只小型猪首次给药后C_(max)为(2.85±0.96)μg·L~(-1),T_(max)为(2.06±0.62)h,t_(1/2)为(8.43±4.13)h,AUC_(0-85)为(23.81±8.62)μg·L·h~(-1),AUC_(0-∞)为(24.36±8.73)μg·L·h~(-1),MRT_(0-85)为(8.40±2.44)h,MRT_(0-∞)为(9.81±3.88)h;末次给药后C_(max)为(2.70±0.55)μg·L~(-1),T_(max)为(1.69±0.65)h,t_(1/2)为(8.51±3.72)h,AUC_(0-85)为(17.71±4.89)μg·L·h~(-1),AUC_(0-∞)为(18.51±4.48)μg·L·h~(-1),MRT_(0-85)为(8.54±3.50)h,MRT_(0-∞)为(9.98±4.41)h。结论:该方法准确、快速、灵敏,专属性强,适用于动物实验及临床上测定血浆中孕三烯酮的浓度及其药代动力学研究。多次给予孕三烯酮胶囊后2 h血药浓度相差不大,且用药后无不良反应,安全性较高。
[Abstract]:Aim: to establish a rapid and sensitive HPLC-MS / MS method for the determination of pregnenone in plasma of Bama miniature pigs and to study the pharmacokinetics of pregnenone capsules in Bama miniature pigs. Methods: Bama miniature pigs were used as experimental animals for 12 weeks, twice a week. Blood samples were collected at different time points after administration. The pharmacokinetic parameters were calculated by determining the concentration of pregnenone in plasma of miniature pigs after repeated administration. The plasma samples were analyzed by LC-MS / MS after extraction of cyclohexane liquid with pregnenone as internal standard. The mobile phase consisted of water (0.1% formic acid) -acetonitrile (0.1% formic acid) and acetonitrile (0.1% formic acid), gradient elution; flow rate: 0.40 mL 路min ~ (-1); injection volume: 20 渭 L; column temperature: 35 鈩，

本文编号：2063958