Identification, Synthesis, and Characterization of Novel Baricitinib Impurities
Guruswamy Vaddamanu1,2, Anandarup Goswami1, N Ravi Sekhar Reddy2
1Department of Chemistry, School of Applied Science and Humanities, Vignan's Foundation for Science, Technology and Research (Deemed to be University), Vadlamudi, Guntur 522 213, India.
ACS Omega
|March 20, 2023
Summary
Three unknown impurities in baricitinib synthesis, including lactone impurity (BCL), dimer impurity (BCD), and hydroxymethyl impurity (BHM), were identified and characterized. These compounds are crucial for developing highly pure baricitinib drug substance.
Area of Science:
- Pharmaceutical Chemistry
- Analytical Chemistry
- Organic Synthesis
Background:
- Baricitinib is a Janus kinase inhibitor used for rheumatoid arthritis treatment.
- Ensuring drug purity is critical for pharmaceutical efficacy and safety.
- Impurities can arise during the synthesis of active pharmaceutical ingredients.
Purpose of the Study:
- To identify and characterize unknown impurities in baricitinib synthesis.
- To elucidate the formation mechanism of the lactone impurity.
- To provide essential reference standards for baricitinib quality control.
Main Methods:
- High-performance liquid chromatography (HPLC) for impurity detection.
- Isolation and structural elucidation using NMR (1H, 13C) and mass spectrometry.
- Synthesis of identified impurities for confirmation.
Main Results:
- Three impurities were identified: lactone impurity (BCL), dimer impurity (BCD), and hydroxymethyl impurity (BHM).
- Impurity levels were found to be between 0.10% and 0.15%.
- Structures were confirmed via spectroscopic analysis, and a plausible mechanism for lactone impurity formation was proposed.
Conclusions:
- The identified impurities are critical for process and formulation development of baricitinib.
- Characterized impurities can serve as vital reference standards for synthesizing high-purity baricitinib.
- This study enhances the quality control and safety of baricitinib production.
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