Solution Stability in Method Validations

1.0 OBJECTIVE                    

To provide the procedure for the verification of Solution Stability in Method Validations.

2.0 SCOPE

This procedure is Applicable to the for the verification of Solution Stability in Method Validations.

3.0 RESPONSIBILITY 

3.1 QC-Chemist 

4.0 ACCOUNTABILITY         

4.1 Executive – Quality control

4.2 Head – Quality control

5.0 PROCEDURE       

5.1 Solution Stability  

During HPLC analysis we are going to prepare the solutions such as mobile phase, diluent,  different sample and standard preparations.We need to verify the solutions should be stable till our analysis is  completed. 

5.2 Why do we need solution stability test in method validation?.

The reasons might be the following

5.2.1. Autosamplers

Autosamplers usage is most common in modern day chromatographic analysis. That means samples injections will be done automatically one by one based on the sequence kept in the autosampler. So the chromatographer can prepare all the samples at a time and keep the samples in the autosampler tray.

As the run time of the injection may vary from about 20-30 minutes, 20-30 samples analysis may take more than a day. But we need to see that the sample should be stable till that time of analysis.

 

5.2.3 . Protect from light

Photosensitive drug substances need to protect from light during the analysis. Prolonged exposure to light may induce oxidation in the drug substances. Analysis might be performed by covering the sampler tray with Black paper or cloth.

5.2.4  Others

Some drug substances need special storage condition such as refrigeration etc…

5.3 How to do that

Stability is determined by comparing the response and impurity profile from aged standards or samples to that of a freshly prepared standard and to its own response from earlier time points.

5.3.1 Experimental design  

Standard and sample solutions stored in a capped volumetric flask on a lab bench under normal lighting conditions for 24 hours to 48 hours based on the stability. 

Perform the analysis by injecting same sample solution at different time intervals. Sample Solution Stability should be monitor up to 24 hrs with minimum 4-5 time intervals or 48 hours with minimum 8-10 intervals. Perform more time intervals after 12 Hrs. Based on Injection run time and sequence time establish the sample solution stability for about 24 Hrs or 48 hours.

5.2.2 Injection Sequence for the stability of analytical solutions.

Inject blank(diluent), Standard solution and Test preparation on every time of 0,5,10,15,20 and 24th hour for 24 hour solution stability.

Inject blank(diluent), Standard solution and Test preparation on every time of 0, 10, 15, 20, 25, 30, 35, 40, 45, 48th hour for 48 hour solution stability.

Measure the peak responses and compare the response with the 0 th hour response.

5.3.3 Acceptance Criteria:

The %RSD of peak response for the major peak for sample solution and impurity at periodic intervals should not be more than 2.0%.

The % Assay and Impurity content of the sample should be within the acceptance criteria.

The % Relative Standard deviation for solution stability from '0' Hrs to '48' Hrs Assay or impurity results should not be more than 2.0.

6.0 ANNEXURES

Nil