How to transfer manual titration to autotitration

Manual titration is a common analysis method in many labs. However, it has several drawbacks, such as subjective endpoint detection, risk for manual errors, or lack of data integrity. In this article, learn the most important steps to consider when converting manual titration to automatic titration, from the choice of the titrator to the optimization of the method itself. 

To jump directly to a topic, click on the link below:

• Disadvantages of manual titration
• What is autotitration?
• Choice of titrator
• Choice of sensor
• Optimizing the sample size and solution volumes
• Selecting the right titration mode
• Optimizing the titration setup and method
• Validation of the method

Disadvantages of manual titration

Manual titration involves adding titrant dropwise from a buret to a sample solution. Endpoint detection is typically done visually (by eye) using color indicators. This analytical method remains widely used because it requires only a glass buret and a flask. However, it comes with several notable disadvantages.

• Subjective endpoint detection: Visual recognition of the color change depends on individual perception. Each person may interpret color intensity differently, which leads to inconsistent results. This issue becomes more pronounced when working with colored or turbid solutions.
• Drop size accuracy: The precision of the analysis is influenced by the size of each drop. For instance, if the drop size is 50 µL and the total titrant volume is 5 mL, a single drop can cause a variation of approximately 1%.
• Time-consuming process: Manual titration takes considerable time. This includes not only the titration itself, but also cleaning and refilling the buret and manually calculating the results. These steps limit the number of samples that can be processed during a shift. 
• Data integrity risks: When performing manual titrations, results are often recorded by hand, transferred to spreadsheets, and then manually entered into a LIMS. Each step introduces potential for human error and requires thorough quality control checks. This process is both tedious and inefficient.

Using an automatic titrator (autotitrator) helps operators to overcome these limitations.

Choice of titrator

When choosing a titrator, you should take several key points into account.

• GLP/GMP compliance: Autotitrators must be able to document results. This includes providing options for a printer connection or digital storage (e.g., USB flash drive). All Metrohm titrators meet GLP and GMP requirements.
• FDA compliance: In regulated environments, titrators must comply with FDA Regulation 21 CFR Part 11. 
• Control options: Titrators can be controlled either via software or an integrated touch display.
• Sample throughput: If a high number of samples are analyzed daily, an automated system can significantly improve laboratory efficiency. Learn more about automation in the article «Why consider automation – even for simple titrations».
• Flexibility for different titrations: Switching between titration types, for example from redox to acid-base titration, requires changing both titrant and electrode. Not all titrators support this. Efficiency improves with titration systems that can be extended with additional burets and electrodes.

Metrohm offers several titrator models with different capabilities. Table 2 provides a comparison of the key points mentioned above for each titrator family.

Choice of sensor

Using a potentiometric electrode is often simpler, as it does not require an indicator solution. However, selecting the correct electrode depends on several factors.

• Chemical reaction: The chemical reaction determines the choice of electrode. For example, acid-base titrations require a pH electrode, while redox titrations require a metal electrode.
• Sample matrix: The sample matrix can significantly affect the electrode performance. For example, protein-containing samples (e.g., dairy products) require a pH electrode with a diaphragm that is insensitive to proteins.
• Sample volume: For small sample volumes, specialized micro electrodes are recommended.

More information about different electrodes for various titration types is available in the article «Best practice for electrodes in titration». 

The flyer «Electrodes for titration» offers guidance on selecting the most suitable electrode. Alternatively, the Electrode Finder allows filtering by the reaction type, application area, or specific details, such as sample matrix.

Optimizing the sample size and solution volumes

When performing manual titrations, reaching the endpoint often requires 30 mL or even 40 mL of titrant. Autotitrators, which have a higher dosing accuracy, are typically equipped with 10 mL or 20 mL burets. Because refilling the buret during titration causes errors, the sample size should be adjusted for automatic titrations. 

For automatic titrators, it is generally recommended that the equivalence point (or expected endpoint volume) should lie between 10% and 90% of the total buret volume. Therefore, a critical step when transferring manual titration to autotitration is the optimization of the sample size. The lower titrant consumption can also save costs.

For example, in the assay of calcium hydroxide, the sample size can be reduced from 1.5 g to 0.375 g. This adjustment decreases the titrant consumption by 30 mL per titration [1]. With an estimated 10 titrations per day, this results in annual savings of approximately €4700 per year on titrant alone. See Table 3 for a detailed example calculation.

Selecting the right titration mode

Some titration reactions are reversible, e.g., acid-base titrations, while others are irreversible, e.g., redox titrations. The speed of the titration reaction can also vary. Therefore, autotitrators are equipped with different titration modes.

There are three commonly used titration modes:

1. Endpoint titration: Titrant is added until a predefined endpoint is reached. This mode is commonly used with a specific pH value as the endpoint.
2. Monotonic titration: A constant volume of titrant is added with each dosing step.
3. Dynamic titration: The volume of titrant added varies depending on the proximity to the equivalence point. Smaller titrant volumes are added incrementally around the equivalence point.

Optimizing the titration setup and method

Optimizing the titration setup and method helps to improve accuracy, speed up the titration, and reduce titrant consumption.

Start volume to speed up the titration

To speed up titrations – especially monotonic titrations – a start volume can be used. This approach resembles the pre-dosing of titrant in manual titration. A pause step should follow the addition of the start volume to allow the titrant to react with the analyte before the titration begins.

Stop volume to save titrant

Applying a stop criterion helps to reduce titrant consumption and minimize waste. The simplest option is a fixed stop volume. This is effective when the equivalence point consistently occurs around the same volume.

For samples with varying analyte concentrations, a more flexible solution is required. In such cases, the maximum number of equivalence points is used as the stop criterion. Additionally, a defined volume should be added afterwards.

In both cases, a stop volume of approximately 1 mL after the equivalence point is recommended.

Validation of the method

The final step in converting manual titration to automatic titration is method validation – especially important in regulated environments. The validation of a titration method includes standardization of the titrant as well as determination of accuracy and precision, linearity, and specificity. For more information about the validation of titration methods, read our blog post «Validation of titration methods».

Conclusion

When transitioning from manual to autotitration, laboratories should consider several key factors. At the same time, this change provides an opportunity to optimize the titration process and reduce waste. The infographic in Figure 5 summarizes the essential steps involved in method transfer:

Reference

[1] Marques, M. R. C.; Pappa, H.; Chang, M.; Spafford, L.; Klein, M.; Meier, L. Recommendations for Converting a Manual Titration Procedure into an Automated Titration Procedure; White Paper WP-063; Metrohm: Herisau, 2021.

Additional resources

Monograph: Practical aspects of modern titration

Blog post: Recognition of endpoints (EP)

Blog post: How to avoid titration errors in your lab

Blog post: Why consider automation – even for simple titrations

Blog post: Validation of titration methods

Blog post: Lab of the future: Automated robotic analysis of petroleum products

On-demand webinar: How to convert from manual to automatic titrations