Mass Spectrometry 2017 Quantification of Temozolomide in Nonhuman Primate Fluids by Isocratic Ultra-High Performance Liquid Chromatography Tandem Mass Spectrometry to Study Brain Tissue Penetration Following Intranasal or Intravenous Delivery – Cody j Peer - National Cancer Institute NIH.

摘要

A sensitive and selective ultra-highperformance liquid chromatography-Tandem mass spectrometric method wasintroduced for the quantification oftemozolomide (TMZ) in nonhuman primate(NHP) plasma, cerebrospinal fluid (CSF),and brain extracellular fluid (ECF) -microdialysis. Ethyl acetate was to extractthe plasma and CSF samples, usingtheophylline because the internal standard(IS). ECF samples were diluted withacetonitrile prior analysis. TMZ wasseparated on Waters UPLC? BEH C18column with an isocratic mobile phaseammonium acetate (10 mM)-0.1% formicacid/ acetonitrile (30:70, v/v) during apositive-ion multiple reaction monitoringmode (m/z 195.5→137.6 for TMZ; m/z181.5→124.2 for IS). And retention time ofTMZ and theophylline has been 0.45 minwith a complete time of two .5 min. Themethod was validated over the various rangefrom 5–2000 ng/mL in NHP plasma, CSF,and ECF with regard to linearity, accuracy,precision, selectivity, and stability. Thismethod was successfully applied towardsthe measurement of pharmacokineticsamples, various routes of drugadministration.