2. Academic Validation
  3. A validated UPLC-MS/MS method for pharmacokinetic study of inflachromene, a novel microglia inhibitor

A validated UPLC-MS/MS method for pharmacokinetic study of inflachromene, a novel microglia inhibitor

  • J Pharm Biomed Anal. 2019 Mar 20;166:183-188. doi: 10.1016/j.jpba.2019.01.013.
Hwan Hee Lee 1,  So Hee Im 2,  Sunjoo Ahn 2,  Myung Ae Bae 2,  Seung Bum Park 3,  Sang Kyum Kim 4,  Jin Sook Song 5
Affiliations

Affiliations

  • 1 Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea; College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
  • 2 Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
  • 3 Department of Chemistry, Seoul National University, Seoul, Republic of Korea.
  • 4 College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
  • 5 Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea. Electronic address: [email protected].
PMID: 30654206 DOI: 10.1016/j.jpba.2019.01.013
Abstract

Inflachromene (ICM), a novel microglia inhibitor, is under development to treat neuroinflammatory disorders. For the pharmacokinetic evaluation of ICM, we developed quantitative ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method in rat plasma. Protein precipitation method with acetonitrile (ACN) was used for plasma sample preparation. The analyte and carbamazepine (the internal standard) were separated by the chromatography on an ACQUITY UPLC™ BEH C18 column running gradient mobile phase system made up of 0.1% [v/v] formic acid in water and 0.1% [v/v] formic acid in acetonitrile. For the quantification of ICM, the ion transitions, m/z 378.2→187.1 (ICM) and m/z 237.1→194.1 (IS) were monitored in multiple reaction monitoring (MRM) mode. Standard calibration curve showed excellent linearity with the correlation coefficient (R2) of 0.99 within the concentration range of 0.05-10 μg/mL. The precision and accuracy were within acceptable limits (all < 20%). ICM was degraded time and temperature dependently in rat plasma. The analytical method was successfully utilized in a pharmacokinetic study following intravenous and oral administration of ICM in rats.

Keywords

Inflachromene; Method validation; Microglia inhibitor; Pharmacokinetics; Stability; UPLC-MS/MS.

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