Robustness: the parameters worth deliberately varying posts 31–58

Nothing to add, except that this is the answer I would give if asked.

Post #43 answers the question as asked. The question underneath it is different.

A definition problem is doing most of the work in this robustness discussion. Once the term is pinned down I suspect the disagreement mostly goes away and what is left is small.

I would be cautious about generalising from the robustness example above. It is a good example. It is one example.

System suitability is the ongoing evidence that a validated method is still performing. Validation is done once; suitability is done every run, and it is the one that appears on a certificate.

I would not lead a decision with this, but I would not ignore it either.

Two sentences on robustness and then I will stop, because the rest is speculation and the thread is better without mine.

What is documented is narrow. What is inferred from it is broad. The gap between them is where every argument here lives.

Post #47 is the version of this I will quote in future. One addition.

The limit of quantitation determines what the impurity table can honestly contain. Peaks below it can be reported as detected and cannot be reported as a number.

I would want to see it done twice before believing it once.

The distinction between a qualified instrument and a validated method is worth keeping. Both are needed and they fail in different ways.

Anyone who has looked at this more carefully, please correct the record.

I had written a reply contradicting post #48 and deleted it. Here is what survived.

I would rather this thread reach "we do not know" about robustness than reach a confident answer that nobody can support when asked.

On robustness, the part that usually goes wrong is that the question is asked as though it has one answer. It has a range, and the width of the range is the interesting bit.

If you can post the two or three numbers you are working from, several people here will check the arithmetic rather than argue about the conclusion.

Saving this. It is the version I will quote when the question comes round again.

Where a pharmacopoeial monograph exists, a method that follows it inherits a great deal of assurance. Almost nothing discussed here has one.

I am not the right person to answer the follow-up to this.

Robustness: the method gives consistent results when minor parameters vary. Tested by deliberately varying pH, temperature, flow rate, and mobile phase composition within reasonable ranges and demonstrating that results stay within acceptance.

The mechanism is plausible, which is not the same as established.

The arithmetic in post #55 is right; the assumption feeding it is the part to check.

The most useful single question about a method: what would it fail to detect? Every method has an answer and few documents state it.

Robustness has been discussed here with more heat than it deserves, mostly because two definitions have been in play the whole time.