Forced Degradation Analysis of Omeprazole Using CORTECS 2.7 μm Columns
Applications | 2014 | WatersInstrumentation
Forced degradation studies are essential in pharmaceutical development to assess the chemical stability of active pharmaceutical ingredients under stress conditions such as low pH. These studies help identify potential harmful by-products that may form during manufacturing or upon administration, ensuring safety and efficacy of oral dosage forms.
This study demonstrates the application of CORTECS 2.7 µm C18+ columns to perform forced degradation analysis of omeprazole. The goal was to resolve the parent compound and its degradation products, including isobaric species, using a standard HPLC system equipped with ultraviolet (UV) and mass detection.
Omeprazole tablets were crushed and subjected to acidic and neutral degradation:
Chromatographic conditions:
The method separated eight known omeprazole degradants with sharp, symmetrical peaks and maintained system backpressure below 5,000 psi. Two pairs of isobaric compounds (m/z 312.4 and 362.4) were resolved chromatographically. Extracted ion chromatograms confirmed peak identities, and combined mass spectra helped detect co-eluting species and verify component purity.
Core–shell stationary phases combined with low-maintenance mass detectors will expand forced degradation profiling and impurity characterization. Future developments may integrate high-resolution mass spectrometry and automated data analysis to further accelerate pharmaceutical method development and quality control.
The CORTECS C18+ 2.7 µm column paired with UV and QDa detection effectively resolves omeprazole and its degradation products under acidic stress. This approach ensures high resolution, reliable identification, and compatibility with existing HPLC systems, supporting robust stability testing in pharmaceutical analysis.
Consumables, HPLC, LC/MS, LC columns, LC/SQ
IndustriesPharma & Biopharma
ManufacturerWaters
Summary
Importance of the Topic
Forced degradation studies are essential in pharmaceutical development to assess the chemical stability of active pharmaceutical ingredients under stress conditions such as low pH. These studies help identify potential harmful by-products that may form during manufacturing or upon administration, ensuring safety and efficacy of oral dosage forms.
Objectives and Study Overview
This study demonstrates the application of CORTECS 2.7 µm C18+ columns to perform forced degradation analysis of omeprazole. The goal was to resolve the parent compound and its degradation products, including isobaric species, using a standard HPLC system equipped with ultraviolet (UV) and mass detection.
Methodology and Sample Preparation
Omeprazole tablets were crushed and subjected to acidic and neutral degradation:
- Solution A: Tablets treated with 0.1 N HCl for 1.5 hours, neutralized with 0.1 N NaOH.
- Solution B: Tablets diluted with 50:50 methanol:water.
- Both solutions filtered and mixed (approx. 66% A, 34% B) prior to injection.
Chromatographic conditions:
- Column: CORTECS C18+, 2.7 µm, 4.6 × 150 mm.
- Mobile phase: 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B).
- Gradient: 10–78% B in 16.5 min, return to 10% B in 0.1 min, hold 3.4 min.
- Flow rate: 1.2 mL/min; column temperature: 30 °C; detection at 280 nm.
Used Instrumentation
- Waters Alliance e2695 HPLC System with 2998 PDA detector.
- Waters ACQUITY QDa mass detector (ESI+ full scan, 120–420 m/z).
- Empower 3 chromatography data system.
Main Results and Discussion
The method separated eight known omeprazole degradants with sharp, symmetrical peaks and maintained system backpressure below 5,000 psi. Two pairs of isobaric compounds (m/z 312.4 and 362.4) were resolved chromatographically. Extracted ion chromatograms confirmed peak identities, and combined mass spectra helped detect co-eluting species and verify component purity.
Benefits and Practical Applications
- High-resolution separation on standard HPLC equipment using core–shell particle technology.
- Low backpressure enables longer columns for enhanced resolution.
- Rapid and reliable mass identification without routine tuning or calibration.
- Streamlined workflow for method development with minimal training.
Future Trends and Applications
Core–shell stationary phases combined with low-maintenance mass detectors will expand forced degradation profiling and impurity characterization. Future developments may integrate high-resolution mass spectrometry and automated data analysis to further accelerate pharmaceutical method development and quality control.
Conclusion
The CORTECS C18+ 2.7 µm column paired with UV and QDa detection effectively resolves omeprazole and its degradation products under acidic stress. This approach ensures high resolution, reliable identification, and compatibility with existing HPLC systems, supporting robust stability testing in pharmaceutical analysis.
References
- Bozdag S., Calis S., Sumnu M. Formulation and stability evaluation of enteric-coated omeprazole formulations. S.T.P. Pharma Sciences 1999, 9, 321–327.
- Seshadri R.K., Raghavaraju T.V., Chakravarthy I.E. A Single Gradient Stability-Indicating Reversed-Phase LC Method for the Estimation of Impurities in Omeprazole and Domperidone Capsules. Scientia Pharmaceutica 2012, 437–458.
- Rajab A., Touma M., Rudler H., Afonso C., Seuleman M. Slow, spontaneous degradation of lansoprazole, omeprazole and pantoprazole tablets: isolation and structural characterization of the toxic antioxidants 3H-benzimidazole-2-thiones. Pharmazie 2013, 749–754.
- USP Reference Standards Search Results for Omeprazole. United States Pharmacopeia.
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