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目的建立猪血浆中格拉司琼质量浓度液相色谱-串联质谱(LC-MS/MS)检测方法,考察格拉司琼经皮给药后药物动力学行为。方法色谱柱:Diamonsil C18柱(150 mm×4.6 mm,5μm),流动相:甲醇-5 mmol·L-1醋酸铵-甲酸(体积比为45∶55∶0.1),采用液液萃取法,以多反应监测(multiple reaction monitoring,MRM)扫描方式,测定巴马小型猪经皮给予格拉司琼贴剂后血浆中药物的质量浓度。结果猪血浆中格拉司琼质量浓度在0.020~20.0μg·L-1内线性关系良好,r=0.995 9;日内和日间精密度RSD≤13.4%;格拉司琼的平均提取回收率为63.8%~66.7%(n=6),基质效应为101.4%~105.8%(n=6);格拉司琼在巴马小型猪血浆中主要药物动力学参数:t1/2为(18.0±1.4)h,ρmax为(15.3±4.0)μg·L-1,MRT为(91.9±4.9)h,Ke为(0.04±0.00)h-1,AUC0-216为(1.22±0.35)mg·h·L-1,AUC0-∞为(1.23±0.35)mg·h·L-1。结论该方法适用于格拉司琼贴剂在巴马小型猪体内药物动力学行为的研究,贴剂可延长格拉司琼作用时间。
Objective To establish a method for the determination of granisetron hydrochloride in pig plasma by liquid chromatography-tandem mass spectrometry (LC-MS / MS) and investigate the pharmacokinetics of granisetron after transdermal administration. Methods The mobile phase was Diamonsil C18 column (150 mm × 4.6 mm, 5 μm). The mobile phase was methanol-5 mmol·L -1 ammonium acetate-formic acid (volume ratio 45:55:0.1) Multiple reaction monitoring (MRM) scanning was used to determine the plasma concentration of the drug in the Bama miniature pigs after percutaneous administration of granisetron patch. Results The concentration of granisetron in pig plasma was linear within the range of 0.020 ~ 20.0 μg · L-1, r = 0.995 9. The intra-and inter-day RSD was less than 13.4%. The average recovery of granisetron was 63.8% (N = 6). The main pharmacokinetic parameters of granisetron in Bama miniature pigs were: t1 / 2 (18.0 ± 1.4) h, The mean ρmax was (15.3 ± 4.0) μg · L -1, MRT was (91.9 ± 4.9) h, Ke was (0.04 ± 0.00) h-1 and AUC0-216 was (1.22 ± 0.35) mg · h · L -1, AUC0-∞ was (1.23 ± 0.35) mg · h · L-1. Conclusion This method is suitable for the study of pharmacokinetics of granisetron in Bama miniature pigs. The patch can prolong the action time of granisetron.