How to Reduce HPLC Method Development Cost Without Compromising Quality

How to Reduce HPLC Method Development Cost: High-Performance Liquid Chromatography (HPLC) is the most widely used and essential technique in pharmaceutical development. However, the process of developing and validating a robust HPLC method can be time-consuming and expensive.

Fortunately, there are effective ways to streamline your method development while keeping costs under control, without sacrificing quality or compliance. In this skill-based blog, I will discuss steps and procedures to reduce the HPLC method development cost without compromising the quality.

How to Reduce HPLC Method Development Cost Without Compromising Quality?

The following are 11 key steps to reduce the HPLC analysis cost:

1. Clearly Define Your Method Goals Early
2. Use Existing Methods as a Starting Point
3. Use Existing Methods as a Starting Point
4. Use Linear Gradient
5. Try To Reduce Early Experiments
6. Chemistry-Based Column Selection
7. Batch Experiments and Parallel Runs
8. Standardise Mobile Phase Components
9. Document Each Experiment With a Conclusion
10. Verify The Developed Method
11. Expert Tips: Common Method Approach

1. Clearly Define Your Method Goals Early

One of the most overlooked cost-saving steps is proper planning. Before beginning experimental work, define:

• The purpose of the method (e.g., assay, impurity profiling, dissolution)
• The required sensitivity, precision, and accuracy
• Regulatory/ Customer requirements

Adopt QBD (quality by design approach) to avoid unnecessary experiments and method over-design.

2. Use Existing Methods as a Starting Point

Rather than starting from scratch, review literature, pharmacopoeias (USP, EP), or internal databases for similar compounds or formulations. Adapting or modifying existing methods is far more cost-effective than developing new ones.

3. Leverage Software and Modelling Tools

Modern method development software like DryLab, Fusion QbD, or AutoChrom can simulate thousands of chromatographic conditions with just a few experiments. Benefits include:

• Faster optimisation of pH, gradient, temperature, etc.
• Reduced number of physical trials
• Predictive resolution mapping

This drastically reduces solvent, column wear, and analyst time.

4. Use Linear Gradient

Start with linear gradients on short columns using generic conditions (e.g., C18 column, 5–95% acetonitrile gradient). This provides a rapid overview of compound behaviour, helping narrow down optimum conditions quickly.

5. Try To Reduce Early Experiments

Use UHPLC or short columns with smaller particle sizes during development to reduce run times and solvent use. For early-phase scouting, consider low-volume injection and shorter run times — it adds up to significant savings.

6. Chemistry-Based Column Selection

Avoid trial-and-error with dozens of columns. Instead, base column choice on:

• Known physicochemical properties (logP, pKa, etc.)
• Existing data from similar analyses
• Orthogonal selectivity (HILIC vs RP vs ion exchange)

Keep a small, well-curated library of columns covering different retention mechanisms.

7. Batch Experiments and Parallel Runs

Plan your lab work in blocks to minimise idle time and instrument use. If your HPLC system allows, run multiple samples or methods in parallel. Automation and sample queues help reduce analyst labour costs and improve throughput.

8. Standardise Mobile Phase Components

Using commonly stocked mobile phases (e.g., water + acetonitrile or methanol with formic acid or phosphate buffers) simplifies procurement, reduces waste, and speeds up method qualification.

Avoid exotic or unstable reagents unless necessary.

9. Document Each Experiment With a Conclusion

An experienced analyst can spot method flaws early, troubleshoot more effectively, and optimize faster. Likewise, well-documented methods and decision trails avoid redundant work if someone new picks up the project.

Training is an investment that pays back in both speed and quality.

10. Verify The Developed Method

Don’t over-validate. Follow ICH guidelines and focus on fitness-for-purpose. For example, impurity methods may need very low LOD/LOQ, but assay methods may not. Tailor validation depth to your actual regulatory or quality requirements.

11 Expert Tips: Common Method Approach

Try to develop common chromatographic conditions/methods for multiple stages. It will reduce both analysis time and analysis cost.

Case Study

If the route of synthesis (ROS) contains 7 steps, and you have to develop the HPLC method for each stage. To reduce the cost, you should try to develop the same chromatographic conditions (or similar chromatographic conditions using the same buffer, solvent and column) for all steps.

Conclusion

Reducing HPLC method development costs without compromising quality requires both skill and experience. By combining smart planning, the right equipment, and modern development strategies, labs can significantly cut their expenses, often by 30-50%, while still delivering robust, regulatory-compliant practices.

Related:

• Relative Response Factor (RRF) in Pharmaceutical Analysis

Further Reading

• HPLC