目的 建立比格犬血漿中芬太尼的液相色譜-串聯(lián)質(zhì)譜（LC-MS/MS）測定方法，并用于藥動學(xué)研究。方法 采用固相萃取（SPE）法從血漿中提取芬太尼和內(nèi)標(biāo)芬太尼-d5，建立比格犬血漿中芬太尼的LC-MS/MS測定方法，進行特異性、準(zhǔn)確度、精密度、基質(zhì)效應(yīng)、靈敏度、稀釋可靠性、穩(wěn)定性方法學(xué)驗證；8只比格犬，分別單次iv給予芬太尼的生理鹽水溶液400 mg/只，用LC-MS/MS測定給藥后血漿中芬太尼濃度，并用WinNonLin軟件計算藥動學(xué)參數(shù)。結(jié)果 芬太尼的線性范圍為2～1 000 pg/mL，精密度、準(zhǔn)確度、基質(zhì)效應(yīng)、靈敏度、稀釋可靠性、穩(wěn)定性均符合生物樣品分析要求。比格犬體內(nèi)芬太尼藥動學(xué)參數(shù)：t_1/2為（4.53±0.748）h，AUC_0-t為（19 659±3 889）h·ng/mL，CL為（2 259±284）mL/（h·kg），符合二室開放模型。結(jié)論 建立的LC-MS/MS分析方法準(zhǔn)確靈敏，適用于芬太尼的藥動學(xué)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.