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Indian Journal of Pharmaceutical Education and ResearchNOW IN
Article

Identification and Characterization of in vitro Metabolites of Belinostat by Rat Liver Microsomes using Ultra Performance Liquid Chromatography Coupled with Tandem Mass Spectrometry

Parul Grover1, Lovekesh Mehta2★, Tanveer Naved2, Sandeep Kumar3, Gorav Monga4★ Corresponding author

  1. 1Department of Pharmaceutical Sciences, KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad.
  2. 2Department of Pharmaceutical Sciences, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, INDIA.
  3. 3Department of Regulatory Affairs, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, INDIA.
  4. 4Department of DMPK and Bioanalytical, Dabur Research Foundation, Sahibabad, Ghaziabad, Uttar Pradesh, INDIA.

CORRESPONDENCE

Lovekesh Mehta

Department of Pharmaceutical Sciences, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, INDIA.

mehta.lovekesh@gmail.com

Received: 01-06-2021; Revised: 27-08-2021; Accepted: 09-11-2021.

Volume 56, Issue 1S · pp. S58–S66 · PUBLISHED 2022 · DOI: 10.5530/ijper.56.1s.43

View on IJPER original site ↗

ABSTRACT

Objectives: The objective of the present study is to study thein-vitro metabolites of FDA approved anticancer drug, belinostat which is a histone deacetylase inhibitor. Methods: The metabolites were formed by incubating the drug, belinostat with rat liver microsomes, at 37°C for 24 hr. The newly formed metabolites were identified and characterized with the help of ultra-high performance liquid chromatography which is interlinked with tandem quadrupole time-of-flight mass spectrometry. Results: Two Phase-I metabolites were formed which include a belinostat amide (reductive metabolite) and belinostat acid (deaminated belinostat). We then elucidated the structures of the formed metabolites based on LC-MS/MS data which included accurate masses, the fragmentation of ions and chromatographic retention times. Conclusion: This study describes the detailed in-vitro metabolite profiling of belinostat which will be further helpful to predict the in-vivo metabolism of belinostat in the human body. Enzyme kinetic parameters (Km and Vmax) for both the metabolites were also established using different substrate concentrations. The study will be helpful in determining the safety and efficacy of the drug. This will further help in determining the elimination mechanism of belinostat which in turn will assist in predicting the effectiveness and toxicity of the drug.

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    Grover, P., Mehta, L., Naved, T., Kumar, S., & Monga, G. (2022). Identification and Characterization of in vitro Metabolites of Belinostat by Rat Liver Microsomes using Ultra Performance Liquid Chromatography Coupled with Tandem Mass Spectrometry. Indian Journal of Pharmaceutical Education and Research, 56(1S), S58–S66. https://doi.org/10.5530/ijper.56.1s.43