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目的:建立灵敏稳定的HPLC-MS/MS方法,用于测定Beagle犬血浆中的曲美布汀(TM)及N-去甲基曲美布汀(N-TM)含量,并研究曲美布汀片剂在健康Beagle犬体内的药代动力学。方法:样品处理采用液液萃取方法,选择西布曲明(IS)为内标。进行HPLC-MS/MS分析,采用ESI源,MRM离子检测模式,TM、N-TM和IS的检测离子对分别为m/z 388.2→343.2,m/z 374.2→195.2,m/z 280.3→125.1。单剂量给药300 mg后,测定犬血浆中TM及N-TM的浓度,并计算药代动力学参数。结果:血浆中TM及N-TM检测的线性范围分别为1～500 ng.mL-1(r=0.9959),0.2～100 ng.mL-1(r=0.9951),萃取回收率均高于85%,日内、日间RSD均小于10%。犬血浆中TM及N-TM Cmax分别为(192±32.1)ng.mL-1和(47.1±22.6)ng.mL-1,Tmax均为(0.667±0.258)h和(1.08±0.492)h,T1/2分别为为(10.8±4.27)h和(7.06±2.53)h。结论:该方法可简便、高效地测定犬血浆中TM及N-TM浓度,并应用于药代动力学研究。
OBJECTIVE: To establish a sensitive and stable HPLC-MS / MS method for the determination of trimebutine (TM) and N-demethyl trimebutine (N-TM) in Beagle dog plasma and to study the effect of trimebutine Pharmacokinetics of Ting tablet in healthy Beagle dogs. Methods: The samples were treated by liquid-liquid extraction and sibutramine (IS) was selected as internal standard. Analytical HPLC-MS / MS analyzes using ESI source, MRM ion detection mode, TM, N-TM and IS ion pairs were m / z 388.2 → 343.2, m / z 374.2 → 195.2, m / z 280.3 → 125.1 . After single-dose administration of 300 mg, the concentrations of TM and N-TM in plasma of dogs were measured and the pharmacokinetic parameters were calculated. Results: The linear ranges of TM and N-TM in plasma were 1 ~ 500 ng.mL-1 (r = 0.9959) and 0.2-100 ng.mL-1 (r = 0.9951) %, Day, day RSD were less than 10%. The values of TM and N-TM Cmax in dogs were (192 ± 32.1) ng.mL-1 and (47.1 ± 22.6) ng.mL-1, respectively, and the Tmax values were 0.667 ± 0.258 h and 1.08 ± 0.492 h, T1 / 2 were (10.8 ± 4.27) h and (7.06 ± 2.53) h, respectively. Conclusion: This method can be used to determine TM and N-TM concentrations in canine plasma easily and efficiently and to be used in pharmacokinetic studies.