You have to distinguish between "validation" and "qualification". In this case you are using a validated analytical method with a change in sample matrix; therefore, you would want to qualify the method for use with that particular solvent. When people respond with "brief validation" what they really mean is qualification. This could be as simple as spiking the sample in methanol and analyzing the spiked samples to ensure that you are getting recovery. As long as there is no substantive change to the analytical procedure then you will have qualified your change in solvent assuming that you get recovery that meets your QA requirements.

This is common when doing degradation studies (as you are doing), and does not require a full validation study.

In my opinion you should. Because you use the methanol to avoid buffer's effect and it can have an effect on the chromatography example intercations between column phase and analyte (depending of the injection volume).

I don't know USP 37 exactly but in most of norms if you change extraction mode you have to do a new validation.

YES

Hi it is better to do a short validation for the changes you made.

Theoretically if the dissolution solvent can dissolve your sample completely, it shouldn't post a significant changes in your analysis data as the injection volume of sample usually are small (0.5 - 1.0ml).

However that is only in an ideal system, and just theoretically not practically confirmed yet. As Mr. Jeremy mentioned, it might have effect on the column during your elution of sample. It is always better to validate the method even with a small changes as it may affect your analyte separation, elution time, sharpness of the peak etc.

You also can do a quick comparison between chromatogram of standard solution dissolved in methanol with chromatogram of standard solution dissolved in phosphate buffer. If both chromatograms didn't display any significant difference, you are safe to say your method is still valid even with the change of solvent.

extarcation solent change than column, otherwise no need of the change of the solavent .

thank all of you for your answers.

Because methanol is one component of mobile phase and the injection volume is small, I think that it doesn't affect the analysis much.

Yes please do it

Hong,

I agree with your sentiment but it does not hurt to do a brief validation anytime you change conditions.

You have to distinguish between "validation" and "qualification". In this case you are using a validated analytical method with a change in sample matrix; therefore, you would want to qualify the method for use with that particular solvent. When people respond with "brief validation" what they really mean is qualification. This could be as simple as spiking the sample in methanol and analyzing the spiked samples to ensure that you are getting recovery. As long as there is no substantive change to the analytical procedure then you will have qualified your change in solvent assuming that you get recovery that meets your QA requirements.

This is common when doing degradation studies (as you are doing), and does not require a full validation study.

Thank all of you for your answers. They are really helpful.

Of course, you need because you change one of impotant parameter that can change the reactivity, solvation of components and other properties. This is a mandatory element for characterization of procedure. It is necessary to estimate its contribution to the error (validation procedure).

You're pretty much forced to do this if you are making a fundamental change ie., switching from methanol to acetonitrile, for example, to extract your analyte from the matrix, i.e., plasma. However, I would not think re-validation would be needed if you are merely changing reagent (methanol?) vendors.

Simply you can run a separate methanol run , and identify is there any impact,i.e separate peak and than your standard and sample , rather doing a camplete validation of analytical method you just do system suitability and if you see an impact than

method validation required, otherwise it's fine.

Hi

The solubility of a compound in different solvent are different. I think initially you have to compare the chromatogram of standard compound dissolved in methanol with chromatogram of standard dissolved in phosphate buffer using same HPLC method condition. If there is no significant difference between them, so there is not needed to validation.

I think it's better to do the validation no matter how small the changes are, so we can see your contribution.

Many thanks to all of you.

I have already tried injecting sample which is prepared by dissolving cefdinir in the mixture of methanol and acetonitrile and the bad new is that the result is not good. Therefore now, I have to find another solvent or another mobile phase for assay. And I have another question:

I dissolve directly cefdinir in solid state instead of using cefdinir solution, in NaOH solution and then determine the remaining amount of cefdinir. My problem here is that do I need to chromatograph the standard solution of cefdinir? And can I dissolve standard cefdinir in the solvent which is different from the one I used to prepare cefdinir solution?

It's better that you will dissolve it in the mobile phase buffer solution and doing same for STD and samples hopefully it will bring better results for you

I recommend to try to use the initial version (the study the degradation of cefdinir in basic solution, using of 5% NaOH solution) if it is necessary, and then at first to neutralize pH with a small amount of strong HCl to pH 7, then to dilute the received solution by 10 times with the mobile phase used in USP to concentration of standard solution. At the expense of it it is possible to avoid the negative phenomena on chromatogams connected with solvent replacement.