Avoiding headaches by a straightforward analytical strategy for successful method transfer

Significance of the Topic

Atorvastatin calcium impurity profiling is critical in pharmaceutical quality control to ensure drug safety and efficacy. Reliable method transfer between different HPLC platforms streamlines regulatory compliance, reduces revalidation workload, and enables laboratories to adopt advanced instrumentation.

Objectives and Study Overview

This case study demonstrates transferring the USP monograph impurity assay for atorvastatin calcium from an Agilent 1260 Infinity HPLC to a Thermo Scientific Vanquish Flex UHPLC system. By following a structured protocol, the goal was to confirm that the new UHPLC platform meets USP system suitability criteria and delivers enhanced performance without full revalidation.

Methodology and Instrumentation

Analysts conducted system suitability tests (SST) on both instruments under identical conditions, using USP-compliant mobile phases and reference standards for atorvastatin and related impurities (Compounds A–D). The Agilent setup featured a binary pump, HiP degasser, HiP ALS autosampler, thermostat, column compartment, and diode array detector. The Vanquish Flex assembly comprised a quaternary pump, split sampler, column compartment with active preheater, and LightPipe-equipped diode array detector.

• Column: USP L7 C8 (4.6×250 mm, 5 µm) at 35 °C
• Mobile phase gradient: ACN/THF/ammonium acetate mixtures (6–100 % B)
• Flow rate: 1.5 mL/min; Injection volume: 20 µL; Detection at 244 nm
• Data system: Thermo Scientific SII on Waters Empower 3

Key Results and Discussion

Both systems achieved resolutions above the USP requirement (≥ 1.5) between atorvastatin and impurity B, with comparable peak shapes. The UHPLC platform exhibited a twofold increase in signal-to-noise ratios across all impurities due to reduced pump pulsation and the high-sensitivity LightPipe flow cell. Retention time shifts remained within acceptable relative retention ranges, eliminating the need for gradient adjustments when relative retention is the primary metric.

Practical Benefits and Application

• Streamlined method transfer using existing SST criteria minimized time and resources typically required for full revalidation.
• Enhanced sensitivity on the UHPLC system aids early detection of low-level or unknown impurities, improving quality control robustness.
• Flexibility to adapt official USP methods to modern instrumentation maintains regulatory compliance while leveraging improved performance.

Future Trends and Opportunities

Analytical laboratories are increasingly migrating to UHPLC platforms to benefit from higher throughput, lower solvent consumption, and improved sensitivity. Advancements in column chemistries, detector technologies, and data analytics will further optimize impurity profiling workflows. Automated method transfer tools and harmonized industry guidelines are expected to simplify technology adoption.

Conclusion

The case study confirms the Vanquish Flex UHPLC system as a viable alternative for USP atorvastatin impurity analysis, fulfilling system suitability requirements and delivering enhanced sensitivity. Applying a straightforward transfer protocol enables laboratories to modernize methods efficiently, balancing regulatory expectations with technological advances.

References

• Analytical Method Transfer Checklist. ProPharma Group, 2021.
• Thermo Scientific Case Study 000566: Method Transfer onto the Vanquish Platform.
• United States Pharmacopeia USP43-NF38, General Chapter <621> Chromatography, 2021.
• USP43-NF38 Atorvastatin Calcium Organic Impurities Procedure, 2021.