Capillary electrophoresis-mass spectrometry for impurity profiling of basic pharmaceuticals using non-volatile...

Area of Science:

• Analytical Chemistry
• Separation Science
• Mass Spectrometry

Background:

• Coupling capillary electrophoresis (CE) with mass spectrometry (MS) is challenging with non-volatile background electrolytes (BGEs).
• A sheath liquid interface is commonly used, but potential liquid sheath effects can complicate method correlation and impact sensitivity.

Purpose of the Study:

• To develop a generic CE-MS approach using non-volatile BGEs for pharmaceutical impurity profiling.
• To investigate and mitigate the influence of the liquid sheath effect on CE-MS analysis.
• To optimize ESI-MS parameters for maximum sensitivity and stable operation.

Main Methods:

• Development of a generic CE-MS coupling method using a sheath liquid interface.
• Application of a 100 mM TRIS BGE adjusted to pH 2.5 with phosphoric acid.
• Simulation experiments to study the liquid sheath effect on migration behavior.
• Optimization of ESI-MS parameters, including sheath liquid composition, capillary position, and nebulizing pressure.

Main Results:

• Phosphate-based BGEs can be used without significant MS sensitivity loss.
• TRIS-based BGEs improve CE performance, allowing higher injection amounts and maintaining resolution.
• Optimized parameters led to stable operation, 15% RSD reproducibility, and MS detection limits of 0.05% for most compounds.
• The liquid sheath effect was studied and its influence on migration behavior understood.

Conclusions:

• The developed generic CE-MS method is effective for pharmaceutical impurity profiling.
• Non-volatile BGEs, particularly TRIS-based ones, offer advantages in sensitivity and performance for CE-MS.
• CE-MS is a valuable analytical tool for the pharmaceutical industry, providing sensitive and reproducible impurity analysis.