高效液相色谱-串联质谱法测定犬血浆中的普瑞巴林及在药代动力学中的应用

发布时间：2018-05-11 09:50

本文选题：普瑞巴林 + LC-MS/MS　；参考：《中国临床药理学与治疗学》2016年07期

【摘要】：目的:建立并验证一种测定犬血浆中普瑞巴林浓度的高效、灵敏、快速的液相色谱串联质谱(LC-MS/MS)检测方法,并应用于Beagle犬单次口服给予普瑞巴林胶囊后体内的药代动力学研究。方法:犬血浆样品经甲醇沉淀蛋白后,使用Agilent ZORBAX-C18(2.1 mm×150 mm,3.5μm)色谱柱,以含0.1%甲酸的水和甲醇作为流动相进行梯度洗脱。采用电喷雾离子源(ESI)正离子模式下多反应监测模式(MRM)分析测定,普瑞巴林及非那西汀的离子对分别为[M+H]+m/z 160.4→83.3和[M+H]+m/z 180.3→110.2。6只Beagle犬口服给予150 mg普瑞巴林胶囊后采集不同时间点血样,用建立的LC-MS/MS分析方法进行测定。结果:普瑞巴林在30~10 000 ng/m L范围内线性良好(r=0.999 5),提取回收率为101.2%~102.9%,批内与批间精密度符合生物样品的分析要求。Beagle犬口服给予150 mg普瑞巴林胶囊后,Cmax为(25 637.5±2 571.8)ng/m L,Tmax为(1.0±0.5)h,t1/2为(4.4±0.6)h,MRT为(6.7±0.7)h。结论:此方法成功地应用于单次口服给予Beagle犬150 mg普瑞巴林胶囊的药代动力学研究。
[Abstract]:Objective: to establish and verify a high efficient, sensitive and rapid LC-MS / MS method for the determination of PreBahrain in canine plasma, and to study the pharmacokinetics of PreBahrain capsules in Beagle dogs after single oral administration. Methods: the plasma samples of dogs were precipitated by methanol. The chromatographic column was Agilent ZORBAX-C18(2.1 mm 脳 150mm ~ 3. 5 渭 m. The gradient elution was carried out with water containing 0.1% formic acid and methanol as the mobile phase. The multiple reaction monitoring mode (MRM) was used to analyze and determine the electrospray ion source (ESI) positive ion mode. The ion pairs of PreBahrain and Fenaxetine were [M H] m / z 160.4 ~ 83.3 and [M _ H] m / z 180.3 ~ 110.2.6 Beagle dogs respectively. Blood samples were collected at different time points after oral administration of 150mg PreBahrain capsule. The results were determined by the established LC-MS/MS analysis method. Results: the calibration curve was linear in the range of 30 ~ 10 000 ng/m / L, and the recovery rate was 101.2% and 102.9% respectively. The precision of intra- and inter-assay was in line with the analytical requirements of biological samples. After oral administration of 150mg Pregabin capsule, the Cmax of Pregabin was 25 637.5 卤2 571.8)ng/m LTmax 1.0 卤0.5ht1.2 was 4.4 卤0.6hmt1.The MRT was 6.7 卤0.7h. Conclusion: this method has been successfully used to study the pharmacokinetics of Beagle canine 150mg PreBahrain capsule.
【作者单位】：中国药科大学药物代谢动力学重点实验室;中国药科大学药物制剂实验室;皖南医学院第一附属医院弋矶山医院临床药学部;
【基金】：十三五重大专项(2014ZX0950Y004-002) 安徽省教育厅2016年高校优秀青年人才支持计划重点项目(gxyq ZD2016178,gxyq ZD2016179)
【分类号】：R965

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