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Development of LC-MS/MS method for cyanoenone triterpenoid determination to support CNS tissue distribution study
Lynn Tian1, William Lafon1, Qingguo Tian1
1Reata Pharmaceuticals, Inc., 2801 Gateway Dr., Suite 150, Irving, TX 75063, USA.
Abstract:
Aims: Cyanoenone triterpenoids penetrate the CNS, exhibiting biological activity via the nuclear factor E2-related factor (Nrf2) pathway. This is the first report on methods for the quantification of cyanonenone triterpenoids' distribution in various CNS tissues by LC-MS/MS. Materials & methods: The analyte was extracted from brain tissue homogenate using protein precipitation and supported liquid extraction. Results & conclusion: The assay validated a quantification range of 3.00-3000 ng/g in brain tissue samples as low as 5 mg. All parameters, including interference (≤20% at LLOQ) and accuracy/precision (15%, with 20% at LLOQ), met acceptance criteria. This assay supported a CNS distribution study, analyzing more than 10 mouse brain regions successfully.
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