Review of the article „A Sensitive HPLC-MS/MS Method for the Quantification of Selegiline in Beagle Dog Plasma: Application to a Pharmacokinetic Study“, verified by Publons, Web of Science

Abstract

Abstract：Objective：To develop a reliable and sensitive high-performance liquid chromatography - tandem mass spectrometry (HPLC–MS/MS) method for the quantification of selegiline in Beagle dog plasma and apply the validated method to study the pharmacokinetic and bioavailability of selegiline oral lyophilisate in Beagle dogs. Methods: Following alkalization with 1M sodium hydroxide solution, the analyte and zolmitriptan (internal standard, IS) were extracted using tert-butyl methyl ether and separated on the CAPCELL PAK C18 column under isocratic conditions. Mass spectrometer was performed using electrospray ionization (ESI) source in the positive mode. The 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 0.2103 ng/mL. The matrix effect of dog plasma on selegiline signal ranged from 98.8 to 105.6% with mean extraction recovery ranging from 79.0% to 81.4%. Intra- day precision was lower than 6.86% and inter-day precision was lower than 4.63%. Conclusion: The validation results demonstrated the reliability of this bioanalytical method, which had been successfully applied to study the pharmacokinetic and bioavailability of 1.25 mg selegiline oral lyophilisate in Beagle dogs. The pharmacokinetic results were also compared with that following intragastric (i.g) administration. It was found that buccal delivery of selegiline could significantly increase its bioavailability.