Comparative analysis of impurity profiles in rifampicin capsules with different crystal forms using LC-MS/MS

Area of Science:

• Pharmaceutical Chemistry
• Analytical Chemistry
• Chromatography

Background:

• Rifampicin (RIF) is a crucial antibiotic for tuberculosis treatment, classified as critically important by the WHO.
• RIF's polymorphic nature complicates impurity profiling, potentially impacting drug efficacy and safety.
• Existing analytical methods are limited in impurity separation and involve cumbersome procedures.

Purpose of the Study:

• To develop and validate optimized chromatographic methods for Rifampicin impurity analysis.
• To systematically investigate Rifampicin impurity profiles across different crystal forms.
• To establish a robust analytical basis for Rifampicin quality control.

Main Methods:

• Optimization of one-dimensional liquid chromatography (1D-LC) using response surface methodology.
• Development of a high-resolution two-dimensional LC-mass spectrometry (2D-LC-MS/MS) detection method.
• Validation of the 1D-LC method for accuracy, sensitivity, linearity, precision, and repeatability.

Main Results:

• The optimized 1D-LC method achieved high accuracy and sensitivity, quantifying impurities down to 0.25 μg/mL.
• The method demonstrated excellent linearity, recovery (88-101%), and precision (RSD < 5%).
• A total of 25 Rifampicin impurities were identified and their profiles systematically investigated using 2D-LC-MS/MS.

Conclusions:

• The developed LC methods offer a more efficient and comprehensive approach to Rifampicin impurity analysis compared to existing pharmacopoeial methods.
• Systematic impurity profiling provides crucial data for ensuring the quality and safety of Rifampicin.
• This research lays the groundwork for improved quality control strategies for this vital antibiotic.