Development and validation of a sensitive, specific and reproducible uplc-ms/ms method for the quantification of ojt007, a novel anti-leishmanial agent: Application to a pharmacokinetic study

Maria Rincon Nigro, Jing Ma, Ololade Tosin Awosemo, Huan Xie, Omonike Arike Olaleye, Dong Liang

Research output: Contribution to journalArticlepeer-review

Abstract

OJT007 is a methionine aminopeptidase 1 (MetAP1) inhibitor with potent anti-proliferative effects against Leishmania Major. In order to study its pharmacokinetics as a part of the drug development process, a sensitive, specific, and reproducible ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated. Voriconazole was used as the internal standard to generate standard curves ranging from 5 to 1000 ng/mL. The separation was achieved using a UPLC system equipped with an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) with 0.1% formic acid in acetonitrile and 0.1% formic acid in water as the mobile phase under gradient elution at a flow rate of 0.4 mL/min. The mass analysis was performed with a 4000 QTRAP® mass spectrometer using multiple-ion reaction monitoring (MRM) in the positive mode, with the transition of m/z 325 → m/z 205 for OJT007 and m/z 350 → m/z 101 for voriconazole. The intra-and inter-day precision and accuracy were within ±15%. The mean extrac-tion recovery and the matrix effect were 95.1% and 7.96%, respectively, suggesting no significant matrix interfering with the quantification of the drug in rat plasma. This study was successfully used for the pharmacokinetic evaluation of OJT007 using the rat as an animal model.

Original languageEnglish (US)
Article number4624
JournalInternational journal of environmental research and public health
Volume18
Issue number9
DOIs
StatePublished - May 1 2021

Keywords

  • Leishmaniasis
  • OJT007
  • Pharmacokinetics
  • Rats
  • UPLC-MS/MS

ASJC Scopus subject areas

  • Pollution
  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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