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Analytics · Method validation · continued

Repeatability versus intermediate precision posts 61–90

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.

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t.nardoneTL3Regular25 Jun 2025#61

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 rather post the uncertainty than round it away.

7 likes 13mo
IA
i.amankwahTL225 Jun 2025 · edited#62

Confirming post #59 from a second method, which matters more than confirming it from a second person.

Answering the repeatability versus intermediate precision question as asked, then the question I think is meant. As asked: yes, with the qualification below. As meant: it depends on how the first measurement was taken.

1 like 13mo
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j.vandermolenTL3Regular25 Jun 2025#63
batchlog, post #26: The arithmetic in post #23 is right; the assumption feeding it is the part to check. 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. That is… 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.

0 likes in reply to #26 13mo
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a.lindqvistTL225 Jun 2025#64
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g.valckenaereTL3Regular26 Jun 2025#65

No notes. Posting so the count is not one.

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st.dialloTL226 Jun 2025#66
t.ndiaye, post #35: I came in to disagree and I am leaving without a disagreement. Go to post

Small correction to my own earlier position on repeatability versus intermediate precision. I had the units the wrong way round, which changes the conclusion by an order of magnitude and therefore changes it entirely.

0 likes in reply to #35 13mo
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HHidalgoTL2Member26 Jun 2025#67
id.almeida, post #21: 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. I would put the burden of proof on the interesting explanation, not the dull one. Go to post

Post #63 describes the usual case. This is about the unusual one.

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.

The claim is narrower than it sounds, and deliberately so.

26 likes in reply to #21 13mo
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s.teixeiraTL226 Jun 2025#68

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

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taper_tableTL3Regular26 Jun 2025 · edited#69

Post #67 put the caveat in the right place and I want to underline it.

The confident answers on repeatability versus intermediate precision and the well-sourced answers are not the same answers, which is the most useful thing I have learned reading this category.

17 likes 13mo
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t.verhoevenTL226 Jun 2025#70
FFaulkner, post #59: Post #57 answers the question as asked. The question underneath it is different. Whatever the answer on repeatability versus intermediate precision turns out to be, the method for getting there is the same: state the assumption, do the arithmetic in public, invite the correction. 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.

7 likes in reply to #59 13mo
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batchlogTL3Regular26 Jun 2025#71

Post #70 is the version of this I will quote in future. One addition.

The arithmetic on repeatability versus intermediate precision is the easy part and it is where the errors are, which is an uncomfortable combination. Show your working and someone will catch it.

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c.chowdhuryTL226 Jun 2025#72
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two_year_lineTL3Regular27 Jun 2025#73
f.novak, post #32: I had written a reply contradicting post #29 and deleted it. Here is what survived. My understanding of repeatability versus intermediate precision is a few years old and may have been superseded. If it has been, I would genuinely like to know rather than keep repeating it. Go to post

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.

9 likes in reply to #32 13mo
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i.balogunTL227 Jun 2025#74

Answering the question post #73 raises rather than the one it answers.

Offering a way to settle repeatability versus intermediate precision rather than another opinion about it. Two measurements, taken the same way, a fortnight apart. If the difference is within the noise, the question was not answerable at this precision.

20 likes 13mo
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impurity_tableTL3Analytical chemist27 Jun 2025#75

Confirming post #74 from a second method, which matters more than confirming it from a second person.

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.

I have written this out at length because the short version keeps being misread.

0 likes 13mo
SO
s.ostergaardTL227 Jun 2025#76

I had written a reply contradicting post #73 and deleted it. Here is what survived.

A note on how repeatability versus intermediate precision gets discussed rather than on repeatability versus intermediate precision itself: the confident posts get the replies and the careful ones get ignored, and the careful ones have been right more often.

2 likes 13mo
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bias_varianceTL4Biostatistician27 Jun 2025#77
batchlog, post #26: The arithmetic in post #23 is right; the assumption feeding it is the part to check. 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. That is… 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.

14 likes in reply to #26 13mo
DF
d.ferreiraTL227 Jun 2025#78
eire_reader, post #43: Adding a null result on repeatability versus intermediate precision. I looked, carefully, and found nothing, and null results deserve posting precisely because they never are. Go to post

My position on repeatability versus intermediate precision is current rather than settled. I have revised it once already and I expect to again, so treat it accordingly.

28 likes in reply to #43 13mo
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FConsidineTL127 Jun 2025#79
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e.bakkenTL227 Jun 2025#80

Post #76 and I disagree about the size of the effect, not about the direction.

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.

Two people can read the same figure differently here and both be reasonable.

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f.villalobosTL227 Jun 2025 · edited#81

Worth separating two things that post #77 runs together.

The documentation on repeatability versus intermediate precision is better than this thread and I say that as someone who has posted in the thread.

7 likes 13mo
TP
t.pereiraTL228 Jun 2025#82
m.stephanopoulos, post #53: Picking up post #52: that is the part I would want checked first. I would be cautious about generalising from the repeatability versus intermediate precision example above. It is a good example. It is one example. Go to post

This follows post #81 rather than contradicting 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 version I would defend. It is not the version I started with.

1 like in reply to #53 13mo
DO
dr_okonkwoTL4 Moderator28 Jun 2025#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.

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c.grimaldiTL228 Jun 2025#84

That is clearer than the version I had in my head. Thank you.

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PharmNotes_WhitfieldTL4Pharmacist28 Jun 2025#85

Repeatability versus intermediate precision: I would want to see the raw numbers rather than the summary before agreeing. Summaries lose exactly the information that would settle this.

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s.cabreraTL228 Jun 2025#86
unit_conversion, post #47: On post #46 — agreed on the reasoning, with one qualification. Distinguishing three things in the repeatability versus intermediate precision discussion that keep getting used interchangeably: the observation, the proposed mechanism, and the recommendation that gets attached to both. Go to post

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.

0 likes in reply to #47 13mo
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n.abernathyTL328 Jun 2025#87
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n.kuuselaTL228 Jun 2025#88

The reason repeatability versus intermediate precision is hard to answer is that the obvious measurement and the relevant quantity are not the same thing, and substituting one for the other is silent.

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k.kimaniTL228 Jun 2025#89

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).

17 likes 13mo
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septum_entryTL2Member29 Jun 2025 · edited#90

Repeatability versus intermediate precision 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.

7 likes 13mo