Abstract
Objective: The objective of the present study was to investigate the stability of TRZ against different stressors and to prepare impurity profile for potential impurities and degradation products (DPs) formed under stress degradation of TRZ bulk drug and formulation.
 Methods: Three analytical methods were developed; the stability-indicating method that was developed using HPLC instrument with 0.01M ammonium acetate buffer (pH 4.0 using glacial acetic acid (GAA)) and acetonitrile in gradient program. The second method was a UPLC/ESI-MS method using 0.1 % Formic acid in Milli Q water (pH= 2.70) and 0.1%Formic acid in Milli Q water: Acetonitrile (10:90) in gradient program for identification of TRZ and DPs while the third, preparative HPLC method was used for isolation of impurities using (A) 0.05% ammonia (NH3) in water and (B) Acetonitrile+20% mobile phase A in gradient sequence. Gradient sequences are described in the main text.
 Results: The analytical method for stability study was developed and validated using ICH (Q2) R1 guidelines. The result of stability study by stress degradation showed that TRZ was susceptible to degradation in acid (7 DPs), alkaline, neutral (9 DPs) and oxidative conditions (10 DPs); major DPs were identified (where it was possible) and the chemical structure was elucidated by combining the data of ESI/MS, NMR and/or Tandem MS. The Impurity profiling was completed by reporting all the DPs, either major or minor for TRZ bulk drug and formulation.
 Conclusion: The complete Impurity profiling for TRZ is reported for the first time in literature. The study data would be add-on for formulation storage condition and further development.
Highlights
Research of novel therapeutic treatment for TB cure is the interesting and challenging topic for researchers since the TB bacteria M. tuberculosis was identified by Dr Robert Koch in 1882 [1]
1.2million people died due to TB infections (HIV positive and negative) [2]. It shows that survival pattern of bacteria are developed against the antibiotics in human body, bacteria are resistant to certain antibiotics and remains ineffective by those anti-TB drugs; microbiologist and researchers are still working on century-old disease and bacteria
The process-related impurity was observed with bulk drug chromatogram, the chromatograms separating degradation products (DPs) and TRZ in different conditions are shown in fig. 2
Summary
Research of novel therapeutic treatment for TB cure is the interesting and challenging topic for researchers since the TB bacteria M. tuberculosis was identified by Dr Robert Koch in 1882 [1]. 1.2million people died due to TB infections (HIV positive and negative) [2]. It shows that survival pattern of bacteria are developed against the antibiotics in human body, bacteria are resistant to certain antibiotics and remains ineffective by those anti-TB drugs; microbiologist and researchers are still working on century-old disease and bacteria. Terizidone was approved by CDSCO (Central drugs standard control organization) of India in 1981 for treatment of TB, which is synthesized by combining two molecules of D-Cycloserin using a benzene ring. 1. (A and B refers to the D-cycloserin rings)TRZ is indicated in MDR-TB (Multidrug resistance TB) [3] The chemical structure of TRZ is shown in fig. 1. (A and B refers to the D-cycloserin rings)TRZ is indicated in MDR-TB (Multidrug resistance TB) [3]
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