目的 建立比格犬血浆中芬太尼的液相色谱-串联质谱（LC-MS/MS）测定方法，并用于药动学研究。方法 采用固相萃取（SPE）法从血浆中提取芬太尼和内标芬太尼-d5，建立比格犬血浆中芬太尼的LC-MS/MS测定方法，进行特异性、准确度、精密度、基质效应、灵敏度、稀释可靠性、稳定性方法学验证；8只比格犬，分别单次iv给予芬太尼的生理盐水溶液400 mg/只，用LC-MS/MS测定给药后血浆中芬太尼浓度，并用WinNonLin软件计算药动学参数。结果 芬太尼的线性范围为2～1 000 pg/mL，精密度、准确度、基质效应、灵敏度、稀释可靠性、稳定性均符合生物样品分析要求。比格犬体内芬太尼药动学参数：t_1/2为（4.53±0.748）h，AUC_0-t为（19 659±3 889）h·ng/mL，CL为（2 259±284）mL/（h·kg），符合二室开放模型。结论 建立的LC-MS/MS分析方法准确灵敏，适用于芬太尼的药动学研究。

Objective To establish a LC-MS/MS method to determine fentanyl in beagle dog's plasma and study their pharmacokinetics. Method A solid phase extraction (SPE) method was used to extract fentanyl and fentanyl -d5 from the plasma to establish a LC-MS/MS determination method for fentanyl in the plasma of beagle dogs. The specificity, accuracy, precision, matrix effect, sensitivity, dilution reliability, and stability methods were tested. Eight beagle dogs were iv injected with 400 mg of normal saline solution of fentanyl, respectively. Their drug plasma concentration was determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by WinNonLin. Results The liner concentration ranges of fentanyl was 2 - 1 000 pg/mL. Precision, accuracy, matrix effect, sensitivity, dilution reliability, and stability meet the requirements of biological sample analysis. For fentanyl, the pharmacokinetic parameter t_1/2, AUC_0-t, and CL were (4.53 ±0.748) h, (19 659 ±3 889) h·ng/mL, and (2 259 ±284) mL/h/kg, respectively. Conclusion The LC-MS/MS analysis method established in this study was proved to be so accurate and sensitive that it can be applied to the pharmacokinetic study of fentanyl.