Objective: To establish a sensitive and rapid liquid chromatography-mass spectrometry (LC-MS/ MS) method for the determination of rasagiline in human plasma and apply to bioequivalence evaluation of two rasagiline mesylate tablets in healthy Chinese subjects. Methods: Liquid-liquid extraction was used to separate rasagiline from plasma in 96-well plate. Separation was performed on ACE C18 (2.1 mm ×100 mm,5 μm) column with the mobile phase of 5 mmol·L-1 ammonium acetate aqueous solution and acetonitrile contained 0.1% formic acid at a flow rate of 0.5 mL·min-1.Under the positive electrospray ionization interface, the multiple reaction monitoring transitions of m/z 172.1→117.0 and m/z 175.1→117.0 were used to measure rasagiline and rasagiline-13C3, respectively. Results: The lower limit of quantification (LOQ) was identifiable and reproducible at 0.020 ng·mL-1, using 150 μL plasma sample. The intra-run and inter-run precision were less than 12.8%, and the accuracy was within ±4.7%. The main pharmacokinetic parameters of rasagiline after a single oral dose of rasagiline tablet under fasting condition for T and R were as follows: Cmax were (8.528±3.595) ng·mL-1 and (8.873±4.128) ng·mL-1; AUC0-t were (5.838±1.660) ng·h·mL-1 and (5.911±1.797) ng·h·mL-1, and AUC0-∞ were (5.990±1.716) ng·h·mL-1 and (6.104±1.895) ng·h·mL-1, respectively. The 90% CIs for the geometric mean ratios of Cmax, AUC0-t and AUC0-∞ of T and R under fasting condition were 88.26%-108.46%, 94.16%-105.35% and 93.55%-105.01%, respectively. The main pharmacokinetic parameters of rasagiline under fed condition for T and R were as follows: Cmax were (4.333±2.434) ng·mL-1 and (4.359±2.980) ng·mL-1, AUC0-t (4.931±1.361) ng·h·mL-1 and (4.807±1.382) ng·h·mL-1, and AUC0-∞ (5.011±1.386) ng·h·mL-1 and (4.893±1.403) ng·h·mL-1. The 90% CIs for the geometric mean ratios of Cmax, AUC0-t and AUC0-∞ of T and R under fed condition were 89.54%-118.23%, 99.88%-107.07% and 99.59%-107.05%, respectively. The results demonstrated the bioequivalence of the rasagiline tablets between T and R. Conclusion: This method has high sensitivity and simple pre-processing procedure, which is suitable for the high-throughput analysis of rasagiline biological samples. The validated method has been successfully applied to a clinical bioequivalence study of two rasagiline mesylate tablets in healthy human subjects, and provides the data support of generic drugs for clinical application.
YU Jing, FENG Xiao-hui, QI Qi, WANG Ju-xiang, DONG Jing, LI Li, ZHANG Peng
. Determination of rasagiline concentration in human plasma by LC-MS/MS and application to bioequivalence study[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(11)
: 1914
-1922
.
DOI: 10.16155/j.0254-1793.2021.11.08
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