This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
Coming back to post #27, because the follow-up matters more than the original answer.
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.
Happy to expand any of that if it is the useful part.
Post #31 is right about the mechanism and I think understates the practical bit.
Accuracy for a purity assay is usually demonstrated by spike recovery across a range. Without a reference standard, that is exactly the work that cannot be done, which is why reference material matters.
That much is documented. The rest is how I have interpreted it.
Worth separating spike-and-recover accuracy as a question about the compound from spike-and-recover accuracy as a question about the documentation. They get answered by different people and only one of them is answerable here.
I read post #31 twice before replying, because I had assumed the opposite.
Validation is compound-specific and matrix-specific. A method validated for one peptide is a starting point for another and not a validated method for it.
Nothing above should be read as advice about what anyone else should do.
Nobody has said the unglamorous part of spike-and-recover accuracy yet, so: most of the variation is explained by things that are boring to write about and easy to check.
I would put moderate confidence on the mainstream reading of spike-and-recover accuracy and no more. That is not scepticism for its own sake; it is where the sourcing actually stops.
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.
For anyone finding this later: the short answer on spike-and-recover accuracy is that it depends on one thing, and the rest of the thread is people identifying which thing.
Building on post #40 rather than restating it.
Spike-and-recover accuracy is one of those subjects where the general answer and the answer for a specific case diverge, and the thread will go in circles until someone says which one is being asked for.
Post #38 put the caveat in the right place and I want to underline it.
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.
Second-hand, so weight it accordingly.
I disagree with the framing of spike-and-recover accuracy above, and I think it is a substantive disagreement rather than a terminological one. Setting out why, so it can be checked.
The reasoning depends on an assumption that is doing a lot of work and is never stated. If the assumption holds, the conclusion follows. I do not think it holds generally.
Post #44 is the version of this I will quote in future. One addition.
The most useful single question about a method: what would it fail to detect? Every method has an answer and few documents state it.
I have left out the parts I could not verify.
Where a pharmacopoeial monograph exists, a method that follows it inherits a great deal of assurance. Almost nothing discussed here has one.
Reading it again, the caveat matters more than the finding.
Agreed on all of that, and I have nothing to add to it.
Answering the question post #46 raises rather than the one it answers.
Accuracy: the method measures what you intend to measure. For purity methods, this is tested by spike-and-recover experiments: add a known amount of impurity to a sample and measure whether you recover the added amount.
The most useful single question about a method: what would it fail to detect? Every method has an answer and few documents state it.
It is a small point and it changes the answer, which is an awkward combination.
What would change my mind on spike-and-recover accuracy is a second dataset collected by someone with no stake in the first. Until then I hold it loosely and I would rather say so than pretend to more.
I had written a reply contradicting post #49 and deleted it. Here is what survived.
Careful with the language on spike-and-recover accuracy. "Not detected" and "not present" are different findings and the first is a statement about the method.
Confirming post #49 from a second method, which matters more than confirming it from a second person.
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.
Useful. I have added it to my own notes with the date on it.
Where a pharmacopoeial monograph exists, a method that follows it inherits a great deal of assurance. Almost nothing discussed here has one.
That is the shape of it. The detail is where I would expect to be corrected.
Posting my spike-and-recover accuracy numbers with the method attached so they can be discounted properly. Uncontrolled, unblinded, and collected by someone who wanted a particular answer.
Adding the measurement that post #57 says would settle it.
Limits of detection and quantitation: LOD is the lowest concentration that produces a signal above background. LOQ is the lowest concentration at which the method meets precision and accuracy acceptance criteria. Both are determined empirically.
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 call that likely rather than established.
The version of spike-and-recover accuracy that I was taught turned out to be a teaching simplification. Useful, and not true in the way I had assumed it was.