Objective: To establish a fast and sensitive LC-MS/MS method for determination of pramipexole in human plasma and to investigate the bioequivalence between 2 formulations of sustained release tablets. Methods: After addition of internal standard and sodium hydroxide,plasma was extracted by ethyl acetate. The supernatant was transferred and evaporated to dryness under a stream of nitrogen. The residue was re-dissolved,and centrifuged before sample injection. UPLC-MS/MS was performed on an Waters ACQUITY UPLC® HSS T3（2.1 mm×50 mm, 1.8 μm） column with the mobile phase consisting of 20 mmol·L-1 ammonium formate-water（A） and acetonitrile （B） in gradient elution. The flow rate was controlled at 0.3 mL·min-1 and the column temperature was set at 40 ℃ . A mass spectrometer equipped with electrospray ionization source was used and pramipexole（m/z 212.2 → 153.0） was monitored in positive ion MRM mode,with pramipexole-d5dihydrochloride（m/z 217. 0 → 153.0） as internal standard. Results: A fast and sensitive UPLC-MS/MS method for determination of pramipexole in human plasma was established and validated and was applied to bioequivalence study of 2 kinds of sustained release tablets. The standard curves of pramipoxole were linear from 5 to 1 000 pg·mL-1 and the lower limit of quantification was 5 pg·mL-1. The intra-day and inter-day relative standard deviation of qunlity-control samples was less than 8.5%, and the accuracy was in the range of -7.67% and 7.35% in terms of relative error. Recovery,specificity,matrix effect and stability met the guiding principles and criteria of NMPA. The method was successfully applied to a bioequivalence study of pramipexole dihydrochloride sustained release tablets containing 0.375 mg in healthy volunteers. The average Cmax under fasting and fed condition of the reference tablet were 396.50 and 502.76 pg·mL-1. The average Cmax under fasting and fed condition of the test tablet were 412.56 and 472.36 pg·mL-1,separately. Conclusion: The method is sensitive and simple in process,producing well chromatographic performance. The test pramipexole tablet is bioequivalent to the reference tablets.
WEI Bo-ping, LI Sha, ZHANG Jing-yao, WEN Qi, LI Xin-xin, YUAN Jun, ZENG Shi
. Determination of pramipexole in human plasma by UPLC-MS/MS and the bioequivalence study of two sustained release tables[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(4)
: 619
-626
.
DOI: 10.16155/j.0254-1793.2021.04.08
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