Reduced Solvent Use and Analysis Time According to USP Methods

Importance of the Topic

Quality control in pharmaceutical analysis relies on robust liquid chromatography methods that meet regulatory requirements while minimizing resource consumption and analysis time.

Objectives and Overview of the Study

This application note details the transfer of a USP monograph method for the separation of quetiapine and its related impurities from conventional HPLC conditions to UHPLC, using the Agilent 1260 Infinity II Prime LC System. The aim is to comply with USP <621> guidelines while achieving shorter run times, reduced solvent use, and cost savings.

Methodology and Instrumentation

The original method employed an Agilent 1100 Series LC with a 4.6×150 mm, 3.5 µm totally porous column. Transfer to UHPLC conditions used an Agilent 1260 Infinity II Prime LC with superficially porous Poroshell EC-C8 columns (4.6×100 mm and 2.1×100 mm, 2.7 µm). Key adjustments followed USP <621> equations:

• Maintain the L/dp ratio within ±25%/+50% when changing column dimensions
• Scale flow rate by column diameter and particle size
• Adjust injection volume and gradient time according to USP formulas

Instrumentation included:

• Agilent 1100 Series: degasser, quaternary pump, autosampler, column compartment, diode array detector
• Agilent 1260 Infinity II Prime: flexible pump, vial sampler, multicolumn thermostat, high-sensitivity diode array detector with Max-Light cartridge
• Agilent OpenLab CDS software for data acquisition and processing

Main Results and Discussion

UHPLC methods met USP criteria for resolution (≥4.0 and ≥3.0) and tailing factor (<2.0). Compared to the original method, the 4.6×100 mm transfer reduced solvent use per injection by 33.5% and the 2.1×100 mm option by 85.9%, while run time dropped by 48.5% (from 68 min to 35 min). System suitability precision (RSD ≤0.2%) and tailing factors remained within monograph limits. Cost analysis indicated a reduction in cost per injection from $74.40 to $63.84, with an investment break-even after approximately 990 injections (~10 months).

Benefits and Practical Applications of the Method

• Significant reductions in solvent consumption and chemical waste
• Shorter analysis times increase sample throughput
• Lower per-injection costs for QC laboratories
• Continued compliance with USP requirements under more sustainable conditions

Future Trends and Potential Applications

Ongoing trends include broader adoption of UHPLC transfers for legacy methods in pharmaceutical QC, further miniaturization of column formats, and integration of green chemistry principles. Interactive cost calculators and digital lab management tools will support decision-making, while next-generation instruments aim to deliver lower energy and solvent footprints.

Conclusion

Transferring the USP quetiapine impurity method to UHPLC on the Agilent 1260 Infinity II Prime LC System under USP <621> guidelines delivers substantial reductions in solvent use (up to 85.9%), analysis time (48.5%), and operational costs, without compromising chromatographic performance or regulatory compliance. This approach supports laboratory sustainability goals and enhances efficiency in pharmaceutical quality control.

References

1. United States Pharmacopeial Convention. United States Pharmacopeia General Chapter <621> Chromatography. NF, Rockville, MD: USP, 2020.
2. United States Pharmacopeial Convention. USP Monograph on Quetiapine. NF, Rockville, MD: USP, 2023.
3. Rieck F. Do You Know the Environmental Impact of Your HPLC? Agilent Technologies Technical Overview 5994-2335EN, 2022.
4. Anastas PT, Warner JC. Green Chemistry: Theory and Practice; Oxford University Press, 1998.