An observation about spike-and-recover accuracy that I cannot explain and am posting anyway, on the principle that unexplained observations are more useful public than private.
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Analytics · Method validation · continued
Spike-and-recover accuracy for a peptide assay posts 61–90
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
r.bakken, post #46: 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. Go to post
The most useful single question about a method: what would it fail to detect? Every method has an answer and few documents state it.
Worth checking against a second source before it gets quoted onward.
Everything in post #60 holds. The case it does not cover is the one I have.
Stability-indicating method: one that can separate a compound from its degradation products. Critical for assay methods that claim to measure actual degradation (as opposed to purity, which is orthogonal).
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m.dumitru, post #56: 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. Go to post
Post #66 answers the question as asked. The question underneath it is different.
The claim about spike-and-recover accuracy upthread is stronger than its source supports. I have read the source. The source says "associated with" and the post says "causes".
owen.brady, post #5: Post #4 is right about the mechanism and I think understates the practical bit. Where a pharmacopoeial monograph exists, a method that follows it inherits a great deal of assurance. Almost nothing discussed here has one. The step people skip is the one I have spelled out. Go to post
I read post #64 twice before replying, because I had assumed the opposite.
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.
Filing a mild objection to the consensus on spike-and-recover accuracy. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit.
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so.mbeki, post #14: Since spike-and-recover accuracy keeps coming up, it should probably be a maintained page rather than a recurring thread. I am happy to draft it if someone with more direct experience will review it. Go to post
On post #68 — agreed on the reasoning, with one qualification.
Spike-and-recover accuracy was covered in the wiki last year and the page has a review date on it, which is a better starting point than my memory of a thread.
a.iyer, post #36: Sensible. I would want the same detail before I acted on it either. Go to post
Everything in post #71 holds. The case it does not cover is the one I have.
I would call the community position on spike-and-recover accuracy likely rather than established, and I would be comfortable defending that hedge.
Ziegler, post #55: Where I part company with post #54, and it is a narrow parting. What I want from this spike-and-recover accuracy thread is the list of things that would need to be true for the claim to hold. If we can write that list, we can check it. Go to post
Where a pharmacopoeial monograph exists, a method that follows it inherits a great deal of assurance. Almost nothing discussed here has one.
I have deliberately not rounded that, because the rounding is where the argument starts.
bias_variance, post #31: 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. Go to post
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 would treat the number as indicative rather than as a measurement.
Post #75 answers the question as asked. The question underneath it is different.
Practical answer on spike-and-recover accuracy, since the theoretical one is upthread: do the simplest check first, write down the result, and only then decide whether the complicated explanation is needed. It usually is not.
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Worth separating two things that post #75 runs together.
The honest answer on spike-and-recover accuracy is that it depends, and the useful part is the list of what it depends on. Four items, in rough order of how much they matter.
Most people get the first two right and then argue about the fourth.
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I would keep spike-and-recover accuracy and the decision it usually gets used for separate in this thread. They are related and they are not the same question, and merging them is why the last one went badly.
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l.aaltonen, post #59: 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. Go to post
Spike-and-recover accuracy looks different depending on whether you are reading the primary literature or the summaries of it, and the difference is not in our favour.
Post #80 is the version of this I will quote in future. One addition.
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.
It reads as pedantry until the day it does not.
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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.
That is the version I would defend. It is not the version I started with.
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baseline_peak, post #53: Useful. I have added it to my own notes with the date on it. Go to post
On spike-and-recover accuracy the community has more anecdote than the confidence in this thread implies, and I include my own contribution in that.
Building on post #84 rather than restating it.
Spike-and-recover accuracy: I have looked for the primary source twice and failed twice. Either it does not exist or it is somewhere I do not know to look, and I would like to know which.
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Post #86 put the caveat in the right place and I want to underline it.
Where a pharmacopoeial monograph exists, a method that follows it inherits a great deal of assurance. Almost nothing discussed here has one.
Adding this to the thread rather than to the wiki, because I am not confident enough for the wiki.
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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 am aware this is the third time this month I have made this point.
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