Deoxycholic acid method transfer from the Corona ultra RS Charged Aerosol Detector to the Corona Veo (or Vanquish) Charged Aerosol Detector

Significance of the topic

Charged aerosol detection (CAD) has become a key approach for quantifying nonvolatile and semi-volatile analytes in pharmaceutical quality control. Transferring established compendial methods between detector generations ensures continuity in assay performance and compliance with monograph requirements while leveraging advances in detector design.

Goals and overview

This work describes the transfer of the USP 40-NF 35 HPLC-CAD monograph method for deoxycholic acid and its impurities from the Corona ultra RS Detector to the new-generation Corona Veo (Vanquish) CAD. The objectives were to determine optimal acquisition settings on the Veo CAD, demonstrate equivalent or improved system suitability, and verify accurate quantification of API content and impurity profiling.

Methodology and used instrumentation

The method employs a Thermo Scientific Vanquish Flex UHPLC system with:

• System Base Vanquish Flex
• Quaternary Pump F
• Split Sampler FT
• Column Compartment
• Chromeleon CDS 7.2 SR5
• Corona Veo (Vanquish) Charged Aerosol Detector or legacy Corona ultra RS CAD

Chromatographic conditions:

• Column: Acclaim 120 C18, 4.6×150 mm, 3 µm
• Mobile phase A: 0.1% formic acid in water
• Mobile phase B: 0.1% formic acid in acetonitrile
• Gradient: 75:25 to 0:100 (0–24 min), hold, return to 75:25 by 38 min
• Flow rate: 1.0 mL/min; Oven: 30 °C
• Injection: 25 µL

Reagents and standards include USP reference deoxycholic and cholic acids, LC-MS grade acetonitrile, formic acid, and ultrapure water. Calibration and sample solutions ranged from 0.0005 to 0.01 mg/mL.

Main results and discussion

System suitability on both detectors met USP criteria: area %RSD < 3% (0.28% ultra RS; 0.63% Veo) and S/N > 10 (32; 42). Method transfer optimization on Veo CAD found best performance with PFV = 1.20, evaporation temperature 50 °C, and a 5 s digital filter. These settings provided high calibration linearity (R2 = 0.9997, weighted 1/area2) and sensitivity (S/N > 8 at 0.25 µg/mL). Robustness testing confirmed accurate quantification unaffected by injection volume variation.

Benefits and practical application

The Veo CAD matched or improved upon the ultra RS CAD performance, offering enhanced S/N and broad analyte response control. Laboratories can adopt the new detector without revalidating the core chromatographic method or compromising compliance with the USP monograph. This transfer supports continuity of assay results and simplifies implementation of modern instrumentation.

Future trends and possibilities

Ongoing trends include further refinement of detector parameters to extend dynamic range and response uniformity across diverse analytes, integration of CAD with advanced data processing tools, and expansion into impurity profiling of complex biologics. Method transfer principles demonstrated here can guide adoption of next-generation detectors in other compendial assays.

Conclusion

The USP HPLC-CAD method for deoxycholic acid was successfully transferred from Corona ultra RS to Corona Veo (Vanquish) CAD. Optimized settings (PFV = 1.20, Evap T = 50 °C, filter = 5 s) delivered equivalent system suitability, precision, sensitivity, and impurity quantification. Either detector can now be used interchangeably for content and impurity determinations in routine QC.

References

• Bailey B., Gamache P.H., Acworth I.N. Guidelines for Method Transfer and Optimization – from Earlier Model Corona Detectors to Corona Veo Detectors (Thermo Fisher TN157).
• Bailey B. et al. Practical Use of CAD – Achieving Optimal Performance, in Charged Aerosol Detection for Liquid Chromatography and Related Separation Techniques (Wiley, 2017).
• FDA Guidance for Industry: Bioanalytical Method Validation, May 2001.
• Gamache P.H., Kaufman S.L. Principles of Charged Aerosol Detection, in Charged Aerosol Detection for Liquid Chromatography (Wiley, 2017).