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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.

Cody j Peer

A sensitive and selective ultra-high performance liquid chromatography- Tandem mass spectrometric method was introduced for the quantification of temozolomide (TMZ) in nonhuman primate (NHP) plasma, cerebrospinal fluid (CSF), and brain extracellular fluid (ECF) - microdialysis. Ethyl acetate was to extract the plasma and CSF samples, using theophylline because the internal standard (IS). ECF samples were diluted with acetonitrile prior analysis. TMZ was separated on Waters UPLC® BEH C18 column with an isocratic mobile phase ammonium acetate (10 mM)-0.1% formic acid/ acetonitrile (30:70, v/v) during a positive-ion multiple reaction monitoring mode (m/z 195.5→137.6 for TMZ; m/z 181.5→124.2 for IS). And retention time of TMZ and theophylline has been 0.45 min with a complete time of two .5 min. The method was validated over the various range from 5–2000 ng/mL in NHP plasma, CSF, and ECF with regard to linearity, accuracy, precision, selectivity, and stability. This method was successfully applied towards the measurement of pharmacokinetic samples, various routes of drug administration.