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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。
OBJECTIVE: To establish and validate a rapid, sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS / MS) method for the determination of pregabalin in canine plasma and apply it to single oral administration of pregabalin capsules Post-pharmacokinetic study. METHODS: The plasma samples of dogs were precipitated with methanol and eluted with a gradient of 0.1% formic acid in water and methanol as the mobile phase using an Agilent ZORBAX-C18 (2.1 mm × 150 mm, 3.5 μm) column. The ion pair pairs of pregabalin and phenacetin were determined by MRM in electrospray ionization (ESI) positive ion mode, respectively [M + H] + m / z 160.4 → 83.3 and [M + H] + m / z 180.3 → 110.2.6 Beagle dogs were orally administered with 150 mg pregabalin capsules and blood samples were collected at different time points and determined by LC-MS / MS. RESULTS: Pregabalin had a good linearity (r = 0.999 5) in the range of 30 to 10 000 ng / mL with an extraction recovery of 101.2% -102.9%. Intra-assay and inter-batch precision met the analytical requirements of biological samples. After oral administration of 150 mg pregabalin capsules to Beagle dogs, the Cmax was (25 637.5 ± 2 571.8) ng / m L, the Tmax was (1.0 ± 0.5) h and the t 1/2 was (4.4 ± 0.6) h. The MRT was (6.7 ± 0.7) h. Conclusion: This method was successfully applied to the pharmacokinetics study of pregabalin 150mg Beagle dogs administered orally once a day.