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LC-MS/MS analysis of pramipexole in mouse plasma and tissues: elimination of lipid matrix effects using weak cation exchange mode based solid-phase extraction.

Abstract
Intranasal delivery is emerging as a promising alternative for oral or intravenous administration of central nervous system (CNS) drugs, such as pramipexole which is widely used for the treatment of Parkinson's disease. To evaluate the effectiveness of intranasal delivery of pramipexole, preclinical pharmacokinetic and tissue distribution studies following intranasal administration need to be investigated. In this paper, we developed and validated a robust and sensitive LC-MS/MS assay without matrix effect for accurate measurements of pramipexole in mouse plasma and tissue samples. Pramipexole and its stable isotope labeled internal standard (d3-pramipexole) were extracted from biological samples by protein precipitation (PPT) coupled with solid phase extraction (SPE) using weak cation exchange SPE cartridges. Matrix effects were studied using post-column infusion and post-extraction addition experiments by direct monitoring of typical phospholipids including glycerophosphocholines (GPChos) and lysoglycerophosphocholines (Lyso-GPChos). Chromatographic separation was achieved on a Welch Ultimate(®) XB-CN column using isocratic elution with a run time of 3.0 min. The assay was linear in the concentration range of 0.05-100 ng/mL and the intra- and inter-day precision and accuracy met the acceptance criteria. Compared with previous reported assays, the current sample preparation approach exhibited significant reduction of matrix effects due to the dramatically decreased levels of residual matrix components such as GPChos and Lyso-GPChos. This method has been successfully applied to pharmacokinetic and tissue distribution studies of pramipexole in mice following a single intravenous or intranasal dose of 50 μg/kg.
AuthorsWeilin Guo, Gao Li, Yanxia Yang, Conglian Yang, Luqin Si, Jiangeng Huang
JournalJournal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 988 Pg. 157-65 (Apr 15 2015) ISSN: 1873-376X [Electronic] Netherlands
PMID25777479 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier B.V. All rights reserved.
Chemical References
  • Benzothiazoles
  • pramipexole
Topics
  • Administration, Intranasal
  • Animals
  • Benzothiazoles (administration & dosage, analysis, blood, pharmacokinetics)
  • Brain Chemistry
  • Chromatography, Ion Exchange (methods)
  • Limit of Detection
  • Linear Models
  • Mice
  • Reproducibility of Results
  • Solid Phase Extraction (methods)
  • Tandem Mass Spectrometry (methods)
  • Tissue Distribution

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