To address LOQ, prepare samples n>=3. The RSD should be >=15%. Repeat on the next day to see if you are getting consistent results. If you are getting higher RSD at higher concentrations, you did something wrong. Re-prepare solutions and samples, clean the vessels. Impurities might interfere with your titration.

I think that the accuracy of LOD/LOQ values depends on the the following factors

1- Type of titration it self ( classical or semi-instrumental method)

when performing acid/base titration using Ph.Ph indicator to detrmining the endpoint is less accurate compared with potentiometric method. So, the best method i think is to construct at least 3 calibration curves and calculate the LOD and lOQ from linear line parameters.

2- Analyst`s titration skills and experiences: as mentioned above, beside the type of titration the skills of the analyist contribute the accuracyof the method and values of LOD /LOQ .... as skills increases the accuracy of visual method increase.

I reached to LOD value of 0.05 micromole of HCl acid in common acid-base titration with standardized NaOH using accuracy and precision calculations for n=6 for each concentration levels of constructed calibration curves

Dear Andrei Blasko and Mohammad-Jamal A. Shammout ,thanks for your valuable inputs. Andrei Blasko, for the 3 samples I prepare, the expected RSD should be more than or equal to 15%? Is it more than or less than?Can you cite any reference that set this as the RSD limit? This would be helpful for me to justify if anyone say auditor, ask us to provide justification. Mohammad Jamal, we are using potentiometric titration and this is performed by autotitrator.If it is manual titration or pH based, I can attribute the deviation of results to method error but in this case since it is an automated potentiometric titration, i believe less room for errors.

Refer to FDA or ICH guidelines

Equal or more RSD (ICH Q2(R1)). The number depends on your analytical procedure and you need to justify it bases on your data.

Dear Kanapathy Sima,

In the technical paper (https://pdf4pro.com/view/validation-of-titration-methods-bikeitech-com-5a2e5f.html) you used in your assessment, no formulae for statistical evaluation are given and I suspect that you calculated the standard deviation (SD) of the replicate results (without dividing by the mean) rather than the relative standard deviation (RSD). As a result, the inverse concentration dependence of the measure of precision should be obtained. You mentioned that "deviation of actual from theoretical" is calculated, which also casts doubt on the correctness of your calculations of the precision estimate.

Generally, according to IUPAC, the limit of quantification (LOQ) is calculated by multiplying the obtained SD by the factor of 10, which corresponds to the RSD equal to 10 %. The value of 0.3 % for the RSD in defining the "determination limit" has been taken by the producer of titrators quite arbitrarily, since a very good precision can be reached in titrimetric analysis. Experimental determination of the standard deviation at low concentration levels requires attention to some issues such as the choice of suitable samples, the number of replicates (between 6 and 10), and others. For details of the LOD and LOQ evaluations see the EURACHEM validation guide (https://www.eurachem.org/index.php/publications/guides/mv#download)

Best regards,

Rouvim Kadis

Dear Esteemed Colleague,

Greetings. I hope this message finds you in the midst of fruitful scientific endeavors. Your inquiry about determining the Limit of Quantification (LOQ) and Limit of Detection (LOD) for titration processes is both relevant and crucial for ensuring the accuracy and reliability of analytical results. Below, I provide a structured approach to ascertain these important parameters within the context of titration, a fundamental analytical technique widely employed in various fields of chemistry and biochemistry.

Understanding LOQ and LOD

• Limit of Detection (LOD): The smallest concentration or amount of analyte that can be reliably detected by an analytical procedure, but not necessarily quantitated as an exact value.
• Limit of Quantification (LOQ): The smallest concentration or amount of analyte that can be quantitatively determined with suitable precision and accuracy.

Determination of LOD and LOQ in Titration

These calculations are based on the IUPAC recommendations, where the factor 3.3 relates to the LOD under the assumption that the standard deviation of the blank is an adequate estimate of the standard deviation at low concentrations of analyte, and the factor 10 for LOQ accounts for the need for higher confidence in quantitative measurements.

Considerations and Best Practices

• Precision and Accuracy: Ensure that the titration method is well-optimized for precision and accuracy, especially at low analyte concentrations.
• Calibration Curve: Regularly verify the linearity of the calibration curve, particularly in the range encompassing the LOD and LOQ, to ensure reliable extrapolation of these limits.
• Instrument Calibration: Maintain stringent calibration of titration equipment and regular verification of measurement accuracy to uphold the integrity of the LOD and LOQ determinations.
• Reagent Purity: Use high-purity reagents and solvents to minimize background noise and enhance the detection and quantification limits.

Determining the LOD and LOQ for titration procedures is essential for the interpretation and validation of analytical data. By following the outlined approach, you can achieve a robust understanding of the sensitivity and quantitative capabilities of your titration methods.

Should you require further assistance or wish to discuss these concepts in more detail, please do not hesitate to reach out. Your commitment to rigorous analytical standards is commendable and crucial to the advancement of scientific knowledge.

Warm regards.

Check out this protocol list; it might provide additional insights for resolving the issue.