Impurity Analysis of Pharmaceutical Products Using Next-Generation LC Column “Shim-pack Arata™ C18”

Significance of the Topic

High-quality peak shapes and rapid column equilibration are critical for accurate analysis of basic and acidic compounds in pharmaceutical quality control.
Long equilibration times and peak tailing associated with conventional ODS columns can compromise throughput and data reliability, especially under low ionic strength conditions.
The Shim-pack Arata C18 column addresses these challenges by providing improved surface chemistry that reduces analyte–column interactions and accelerates stabilization.

Objectives and Study Overview

This study aimed to compare the performance of the Shim-pack Arata C18 column with a typical ODS column for:

• Analysis of model basic (amitriptyline, dextromethorphan) and acidic (benzoic acid) compounds under low ionic strength mobile phases.
• Impurity profiling of amitriptyline using pharmaceutical impurity standards.

The goal was to evaluate equilibration times, peak symmetry, retention stability, and resolution in both scenarios.

Methodology

Analytes were prepared at 100 mg/L in the respective mobile phases. Two mobile phase systems were used:

• 0.1 % formic acid in water/acetonitrile (70/30, v/v) for basic and acidic compound analysis.
• 0.1 % phosphoric acid in water/acetonitrile (70–76/24, v/v) for impurity testing of amitriptyline.

Chromatographic conditions were held constant: flow rate 0.4 mL/min, column temperature 40 °C, injection volume 1 µL, and dual-wavelength detection at 254/280 nm or 210 nm depending on the test.

Instrumentation

• System: Shimadzu Nexera X2 UHPLC.
• Test columns:
• Shim-pack Arata C18 (75 × 3.0 mm I.D., 2.2 µm).
• Typical ODS column (75 × 3.0 mm I.D., sub-2 µm).

Main Results and Discussion

Under low ionic strength formic acid conditions, the Shim-pack Arata C18 column achieved retention time stabilization within 30 min and peak symmetry factors of 1.07–1.19 for amitriptyline and dextromethorphan. The conventional ODS column required up to 720 min to stabilize, yielding poor symmetry factors of 2.49–3.90.
In impurity analysis, the conventional ODS column exhibited shifting retention and overlapping peaks even after 12 h equilibration. In contrast, Shim-pack Arata C18 delivered consistent retention times and clear separation of five impurities and the main amitriptyline peak after just 5 h, with stability maintained through 12 h.

Benefits and Practical Applications

• Significantly reduced equilibration time enhances laboratory throughput.
• Improved peak symmetry and stable retention increase quantitation accuracy.
• Robust performance under low ionic strength acidic conditions supports reliable LC and LC/MS impurity testing.
• Suitable for routine quality control and high-throughput pharmaceutical analysis.

Future Trends and Potential Applications

Ongoing developments may include further surface modifications to extend compatibility to a broader range of polar and ionizable analytes.
Integration with high-resolution mass spectrometry and automated method development tools will enhance sensitivity and streamline workflow.
Adaptation to green solvents and ultra-fast gradients could further improve sustainability and throughput.

Conclusion

The Shim-pack Arata C18 column demonstrates fast equilibration, excellent peak shapes, and stable retention for both basic and acidic compounds under low ionic strength conditions. Its superior performance in impurity profiling of pharmaceuticals makes it a valuable tool for high-precision QC and research laboratories.