Objective: To develop a reliable and sensitive high-performance liquid chromatographytandem mass spectrometry (HPLC-MS/MS) method for the quantification of selegiline in Beagle dog plasma and apply the validated method to study the pharmacokinetics and bioavailability of oral selegiline lyophilizate in Beagle dogs.

Methods: Following alkalization with 1 M sodium hydroxide solution, selegiline and the Internal Standard (IS) zolmitriptan were extracted using tert-butyl methyl ether and separated on a CAPCELL PAK C18 column under isocratic conditions. They were detected by MS/MS using electrospray ionization (ESI) in the positive mode. Quantification was performed using multiple reaction monitoring (MRM) with transitions of m/z 188.05→90.9 for selegiline and m/z 288.05→57.95 for IS.

Results: Calibration curves were constructed in the concentration range of 0.2–200 ng/mL with a lower limit of quantification (LLOQ) of 0.21 ng/mL. The matrix effect of dog plasma on the selegiline signal ranged from 98.8 to 105.6%, and the mean extraction recovery ranged from 79.0% to 81.4% at concentrations of 1.04, 20.8, and 166 ng/mL. The intra-day precision was lower than 6.86% and the inter-day precisions were lower than 4.63%.

Conclusion: The validation results demonstrated the reliability of this bioanalytical method, which was successfully applied to study the pharmacokinetics and bioavailability of 1.25 mg of orally administered selegiline lyophilizate in Beagle dogs. The pharmacokinetic results were also compared with those obtained following intragastric (i.g.) and intravenous (i.v.) administration. Buccal delivery of selegiline was found to significantly increase its bioavailability.

目的：建立可靠，灵敏的高效液相色谱串联质谱（HPLC-MS / MS）方法定量测定比格犬血浆中司来吉兰的含量，并将验证的方法用于研究口服比色犬血清司来吉兰冻干剂的药代动力学和生物利用度。 。

方法：用1 M氢氧化钠溶液碱化后，使用叔丁基甲基醚萃取司来吉兰和内标（IS）佐米曲普坦，并在等度条件下在CAPCELL PAK C18柱上分离。使用正离子模式下的电喷雾电离（ESI）通过MS / MS检测它们。使用多反应监测（MRM）对司来吉兰进行m / z 188.05→90.9转换，对IS进行m / z 288.05→57.95转换进行定量。

结果：在0.2–200 ng / mL的浓度范围内建立了校正曲线，定量下限（LLOQ）为0.21 ng / mL。在血浆浓度为1.04、20.8和166 ng / mL时，狗血浆对司来吉兰信号的基质作用范围为98.8％至105.6％，平均提取回收率范围为79.0％至81.4％。日内精度低于6.86％，日间精度低于4.63％。

结论：验证结果证明了该生物分析方法的可靠性，该方法已成功用于研究1.25 mg口服司来吉兰冻干物在比格犬中的药代动力学和生物利用度。药代动力学结果也与胃内（ig）和静脉内（iv）给药后获得的结果进行了比较。人们发现，司来吉兰的经颊递送可显着提高其生物利用度。