Ph. Eur. 2.2.46 HPLC Signal to Noise Ratio

[fgleeson]

As per Ph. Eur. 2.2.46 Chromatographic Seperation Technique, Signal To Noise Calculation is calculated as: 2 x Height of Peak/ noise of baseline. We have just noticed that in our validations to date, we have not multiplied the height of the peak by 2, we use the calculation: Height of Peak/ noise of baseline in both our compendial and in house methods.
Is it necessary to follow the compendial calculation or is our calculation adequate.

[krickos]

As per Ph. Eur. 2.2.46 Chromatographic Seperation Technique, Signal To Noise Calculation is calculated as: 2 x Height of Peak/ noise of baseline. We have just noticed that in our validations to date, we have not multiplied the height of the peak by 2, we use the calculation: Height of Peak/ noise of baseline in both our compendial and in house methods.
Is it necessary to follow the compendial calculation or is our calculation adequate.

Hi

As I understand it you do not multiply with 2, otherwise you use the same way of measuring peak height/noise, which leads to that you have a strikter requirement internally provided the S/N limit remains unchanged.

The only problem you might up with is that the S/N test fails when you do it that way but passes when done as per Ph Eur. The likelyhood of this is of course dependent on method/substance response/report limit, but you really do not want to get tangled into a deviation investigation where people want to pass a run where the SST fails/pass depending on the calculation.

So basicly OK but I would not like to explain a deviation as descibed above to a FDA auditor.

[fgleeson]

Hi, thank you for your response,
I should have explained previously that we calculate our Limit of Detection (LOD) and Limit of Quantitation (LOQ) during validation studies using the signal to noise calculation as per ICH Guidelines. By not multiplying by 2, we have underestimated our LOD (calculated LOD of 3 instead OF 6 as per Ph. Eur. calculation) and LOQ (calculated LOQ of 10 instead of 20 as per Ph. Eur. calculation). We have therefore not reached a low enough response (peak area) for each peak of interest. Am I correct by saying this and what is the impact on our valadation studies.

[krickos]

Hi again

Well assuming this has not caused any problem with normal (none genotoxic) impurities reporting limits (0,05 or 0,03% per ICH), I would guess this is not a huge problem. In any case you should consider amending your validation reports that are effected.

If the reports have been submitted to regulatory authorities discuss it with your regulatory people if any updates need to be submitted, hopefully this would fall under "anual reporteble". Likewise you may have to discuss this with your QA people how to document it.

Frankly I have never experianced something similar myself so have a good talk about with your collegues.