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目的:建立HPLC-MS/MS法测定Beagle犬血浆中盐酸格拉司琼的浓度,用于盐酸格拉司琼的浓度测定及药代动力学研究。方法:采用8只健康Beagle犬分别交叉给予0.3 mg.kg-1盐酸格拉司琼片剂和盐酸格拉司琼贴剂,2次给药间隔为2周,不同时间点取血,血浆样品采用液-液萃取法处理。流动相为甲醇-乙腈-pH 4.5醋酸铵缓冲液(12.5 mmol.mL-1)(42∶18∶40),用Zorbax Eclipse XB-C18柱(5μm,150 mm×4.6 mm)色谱柱分离;以盐酸伪麻黄碱为内标。流速0.5 mL.min-1;进样量25μL,柱温为室温。质谱检测采用ESI正离子模式,扫描方式为多反应监测,扫描离子对m/z格拉斯琼313.2/138.1,伪麻黄碱166.1/148.1,用DAS2.1药代动力学软件计算药代动力学参数。结果:盐酸格拉司琼的线性范围为0.005～4 ng.mL-1,线性关系良好(r2=0.9986),最低定量限为0.005 ng.mL-1,回收率在95.3%～107.7%间,变异系数均小于7%。结论:本文所建立的HPLC-MS/MS法灵敏、准确、可靠,可用于犬血浆中盐酸格拉司琼的浓度测定及药代动力学研究。
OBJECTIVE: To establish a HPLC-MS / MS method for the determination of granisetron hydrochloride in plasma of beagle dogs for the determination of concentration and the pharmacokinetics of granisetron hydrochloride. Methods: Eight healthy Beagle dogs were given crossover with 0.3 mg.kg-1 granisetron hydrochloride tablets and granisetron hydrochloride patch respectively. The interval between the two doses was 2 weeks. The blood samples were collected at different time points. - Liquid extraction method. The mobile phase was methanol-acetonitrile-pH 4.5 ammonium acetate buffer (12.5 mmol.mL-1) (42:18:40) and was separated on a Zorbax Eclipse XB-C18 column (5 μm, 150 mm × 4.6 mm) Pseudoephedrine hydrochloride as an internal standard. Flow rate 0.5 mL.min-1; injection volume 25μL, the column temperature was room temperature. Mass spectrometry was performed with ESI positive mode and multi-reaction scanning. Scanning ion pair m / z grasqin 313.2 / 138.1 and pseudoephedrine 166.1 / 148.1 were used to calculate the pharmacokinetic parameters using the DAS 2.1 pharmacokinetic software. Results: Granisetron hydrochloride had a linear range of 0.005 ~ 4 ng.mL-1 with a good linearity (r2 = 0.9986), the lowest limit of quantification was 0.005 ng.mL-1, and the recoveries ranged from 95.3% to 107.7% Coefficients are less than 7%. Conclusion: The established HPLC-MS / MS method is sensitive, accurate and reliable and can be used to determine the concentration and the pharmacokinetics of granisetron hydrochloride in canine plasma.