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Analytics · Method validation · continued

Repeatability versus intermediate precision posts 91–120

This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1 · go to the accepted answer.

SO
s.oyelaranTL229 Jun 2025#91

Picking up post #88: that is the part I would want checked first.

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

The general case is well covered; this is the awkward specific one.

2 likes 13mo
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OTeixeiraTL329 Jun 2025#92
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n.zielinskiTL229 Jun 2025#93
a.asante, post #52: System suitability: injections run at the start of a batch to establish that the instrument and column are performing. Acceptance criteria typically include replicate precision (RSD ≤2%), peak tailing (0.8–1.5), theoretical plates (>2000), and resolution (>1.5). That is my reading. Someone else read the same page differently and was… Go to post

Speaking only to repeatability versus intermediate precision as I have actually seen it, rather than as it is usually described: the effect is real, it is smaller than the thread suggests, and the variance between people is larger than the effect.

20 likes in reply to #52 13mo
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MJayawardenaTL3Regular29 Jun 2025#94
two_year_line, post #73: 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. If anyone has run this properly I would rather read that than my own guess. Go to post

Precision has two levels worth distinguishing: repeatability within a run and intermediate precision across days, analysts and instruments. The second is where most methods lose the numbers people quote.

0 likes in reply to #73 13mo
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b.teixeiraTL229 Jun 2025#95

Following this. I have the same question and no better information than the first post.

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endpoint_marginTL2Member29 Jun 2025#96

The useful distinction on repeatability versus intermediate precision is between what was measured and what was inferred from it. Both end up in the same sentence and only one of them has error bars.

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ar.kravchenkoTL229 Jun 2025 · edited#97

Precision and repeatability: within-run and between-run variability of the method. Acceptance criterion is typically a relative standard deviation of ≤2% for area measurements.

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e.dalgleishTL3Regular29 Jun 2025#98
s.cabrera, post #86: Taking post #85 at face value and following it one step further. Precision has two levels worth distinguishing: repeatability within a run and intermediate precision across days, analysts and instruments. The second is where most methods lose the numbers people quote. A qualification I should have led with rather than closed on. Go to post

What would change my mind on repeatability versus intermediate precision 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.

28 likes in reply to #86 13mo
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ka.haddadTL230 Jun 2025#99

A request rather than an answer: could whoever has the primary source for repeatability versus intermediate precision post it? I have seen the claim three times this month and each version had lost a qualifier.

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a.salcedoTL3Regular30 Jun 2025#100

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.

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ambient_reviewTL3Regular30 Jun 2025#101

Adding the measurement that post #98 says would settle it.

I read the earlier replies on repeatability versus intermediate precision twice before writing this, because I had assumed the opposite and wanted to be sure I was disagreeing with what was said rather than what I expected.

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a.petrovTL230 Jun 2025#102

Post #100 describes the usual case. This is about the unusual one.

Repeatability versus intermediate precision came up in a thread eighteen months ago and was answered well. I cannot find it, which is itself the problem, so here is the reconstruction.

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j.habermannTL3Regular30 Jun 2025#103
t.verhoeven, post #70: The most useful single question about a method: what would it fail to detect? Every method has an answer and few documents state it. Go to post

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.

I would rather say I do not know than round it up to an answer.

13 likes in reply to #70 13mo
NS
ni.stanescuTL230 Jun 2025#104
n.zielinski, post #93: Speaking only to repeatability versus intermediate precision as I have actually seen it, rather than as it is usually described: the effect is real, it is smaller than the thread suggests, and the variance between people is larger than the effect. Go to post

An independent laboratory's method being different from the supplier's is not a discrepancy. It becomes one only when the results differ by more than both methods' demonstrated precision.

27 likes in reply to #93 13mo
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n.torrenceTL3Regular30 Jun 2025#105

Picking up post #102: that is the part I would want checked first.

If you are new and reading this thread for the answer to repeatability versus intermediate precision: the answer is conditional, the conditions are in the third reply, and the rest of the thread is worth skipping.

0 likes 13mo
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k.agyemanTL230 Jun 2025#106

Reporting a result to more decimal places than the method's precision supports is a small dishonesty that appears everywhere. A method with a two per cent relative standard deviation does not support a figure quoted to a hundredth.

If that is already documented somewhere, ignore me and link it.

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s.poulsenTL3Regular30 Jun 2025 · edited#107
dr_okonkwo, post #83: 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. Go to post

Worth stating the null on repeatability versus intermediate precision before we explain it: the observation may be nothing. That possibility deserves a sentence and usually does not get one.

8 likes in reply to #83 13mo
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mi.almeidaTL21 Jul 2025#108

Coming back to post #104, because the follow-up matters more than the original answer.

Second-hand on repeatability versus intermediate precision, so weight it accordingly — someone whose method I trust told me this and I have not verified it myself.

20 likes 13mo
RM
r.marsdenTL3Regular1 Jul 2025#109
i.lehtinen, post #48: Picking up post #46: that is the part I would want checked first. The most useful single question about a method: what would it fail to detect? Every method has an answer and few documents state it. Where I would look next, rather than where I would stop. Go to post

Precision and repeatability: within-run and between-run variability of the method. Acceptance criterion is typically a relative standard deviation of ≤2% for area measurements.

I would put a moderate confidence on that and no more.

28 likes in reply to #48 13mo
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n.serranoTL21 Jul 2025#110

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

It is the kind of thing that is obvious once and never again.

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peak_purityTL3Analytical chemist1 Jul 2025 · edited#111

The question underneath repeatability versus intermediate precision is usually "how would I tell?" rather than "what is true?", and that one has a method attached to it.

Write down what you would expect to see under each hypothesis before you collect anything. If they predict the same observation, collecting it will not help.

1 like 13mo
SD
s.dialloTL21 Jul 2025#112
e.dalgleish, post #98: What would change my mind on repeatability versus intermediate precision 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. Go to post

Reading rather than answering, but this is the post I would point somebody at.

0 likes in reply to #98 13mo
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np_gilmoreTL3Nurse practitioner1 Jul 2025#113

Coming back to post #111, because the follow-up matters more than the original answer.

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.

Happy to be the one who is wrong here if it settles the question.

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j.erdoganTL21 Jul 2025#114

Post #111 is right about the mechanism and I think understates the practical bit.

An independent laboratory's method being different from the supplier's is not a discrepancy. It becomes one only when the results differ by more than both methods' demonstrated precision.

That is where I would start, not where I would stop.

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MP
mira.patelTL4 Admin1 Jul 2025#115
d.oyelaran, post #24: The most useful single question about a method: what would it fail to detect? Every method has an answer and few documents state it. Go to post

Adding the boring version of repeatability versus intermediate precision, because the interesting version keeps getting posted and the boring one is usually right.

Check the ordinary explanations, in order, and stop when one of them accounts for what you are seeing. Most of the time the second one does.

4 likes in reply to #24 13mo
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g.rasmussenTL21 Jul 2025#116
np_gilmore, post #113: Coming back to post #111, because the follow-up matters more than the original answer. 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. Happy to be the one who is wrong here if it settles the… Go to post

Before the thread moves on from repeatability versus intermediate precision — what is the sample size behind the claim? I am not being difficult; I have seen the same figure quoted from an n of four and from an n of four hundred.

0 likes in reply to #113 13mo
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owen.bradyTL4 Moderator2 Jul 2025#117

I read post #115 twice before replying, because I had assumed the opposite.

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

The strength of my opinion here exceeds the strength of my evidence.

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MO
m.onwukaTL22 Jul 2025#118

Where I have landed on repeatability versus intermediate precision, having got it wrong once in public: the direction is clear, the magnitude is not, and anyone quoting a precise magnitude has borrowed it from somewhere that did not measure it.

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h.mensahTL22 Jul 2025#119

That matches what I have seen, for whatever a single anecdote is worth.

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l.piresTL22 Jul 2025#120

Adding the measurement that post #118 says would settle it.

System suitability: injections run at the start of a batch to establish that the instrument and column are performing. Acceptance criteria typically include replicate precision (RSD ≤2%), peak tailing (0.8–1.5), theoretical plates (>2000), and resolution (>1.5).

I have no interest in any supplier named above.

26 likes 13mo