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Analytics · HPLC & UHPLC · continued

Carryover and the ghost peak from last week's standard — what changed since 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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PSundbergTL2Member22 Jun 2026#61

This settles it for me, at least until somebody posts a reason it should not.

0 likes 1mo
YE
y.eriksenTL223 Jun 2026#62
aliquot_line, post #56: The number people quote for Carryover is a central estimate presented without its interval, and the interval is wide enough that the estimate is nearly uninformative on its own. Go to post

Post #60 answers the question as asked. The question underneath it is different.

A chromatogram image at a resolution where you can see peak shape but not baseline detail is worth having and is not the same as the data. Ask for the integration table if the number matters.

Noting that the question and the thing people usually mean by it are different.

26 likes in reply to #56 1mo
RM
r.marsdenTL323 Jun 2026#63
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f.fontaineTL223 Jun 2026#64

I read the earlier replies on Carryover 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.

4 likes 1mo
WT
week_threeTL1Member23 Jun 2026#65

Everything in post #62 holds. The case it does not cover is the one I have.

This is why a purity figure without the underlying chromatogram is weaker evidence than it appears. It is also why two competent laboratories can report different numbers on the same vial without either being wrong.

Not a strong opinion, just a consistent one.

0 likes 1mo
JI
j.ivaturiTL224 Jun 2026#66

Summarising the Carryover thread so far, since it is long and the answer is buried: the first reply has the method, the fourth has the correction to it, and the rest is people agreeing at length.

0 likes 1mo
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sterile_tableTL3Regular24 Jun 2026#67
ambient_draft, post #46: What I can speak to on Carryover is narrow, so I will keep it narrow rather than generalising from it. Beyond that boundary I do not know. Go to post

Injection volume matters because column overload distorts peak shape, and an overloaded main peak can swallow a small neighbour. A certificate without injection volume is missing something load-bearing.

18 likes in reply to #46 1mo
GB
g.bakkenTL224 Jun 2026 · edited#68

If two laboratories disagree by more than two or three percentage points, work through method, integration, sample handling, whether it was the same lot and the same vial, and whether suitability passed. After all five, a gap needs an explanation.

7 likes 1mo
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microgramsTL2Regular25 Jun 2026#69
r.marsden, post #63: The honest answer on Carryover 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. Go to post

Carryover is a question about a distribution, not about a value, and treating it as a value is what produces the confident wrong answers.

27 likes in reply to #63 1mo
MR
m.radichTL225 Jun 2026#70
c.rasmussen, post #49: Where the Carryover discussion usually stalls is that nobody wants to say "I do not know" and everyone is willing to say "it varies". Those are the same sentence with different clothes on. Go to post

Change the wavelength and the proportions change even though the sample has not. That is the reason the wavelength has to be on the document for the number to mean anything.

13 likes in reply to #49 1mo
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v.szaboTL3Analytical chemist25 Jun 2026#71

Confirming post #68 from a second method, which matters more than confirming it from a second person.

On Carryover, I would rather understate and be corrected upward than overstate and be quoted. That is a house style here and it is a good one.

29 likes 1mo
NO
n.oseiTL225 Jun 2026#72
sterile_file, post #35: Typical suitability criteria are a replicate area relative standard deviation below about two per cent, a tailing factor inside a defined window, a resolution minimum against a specified peak, and a plate-count floor. Speaking for myself and not for anyone else who has posted here. Go to post

I had written a reply contradicting post #70 and deleted it. Here is what survived.

One caution on Carryover: everything above assumes the underlying documentation is what it claims to be. That assumption is doing real work and is rarely stated.

0 likes in reply to #35 1mo
DO
d.oyelaranTL3Pharmacist26 Jun 2026#73

A shoulder on the trailing edge is most often a closely related species rather than an artefact. The way to find out is to change the gradient slope, not to argue about the integration.

2 likes 1mo
HV
h.vargaTL226 Jun 2026#74

Peak purity: a diode-array detector records a spectrum at every time point. If a peak contains two co-eluting species with different spectra, the spectrum changes across the peak. A passing peak-purity result says the spectrum is constant; it is weak evidence of homogeneity if the impurities have similar spectra.

9 likes 1mo
CL
coldchain_liuTL3Regular26 Jun 2026#75

Before anything else: what was the gradient, and at what wavelength? Area percent at different wavelengths is not the same number even on the same sample because different species absorb differently at different wavelengths. With the method stated, I can tell you something useful. Without it, all I can say is that there is one large peak.

Written from notes rather than memory, which is why the numbers are specific.

0 likes 1mo
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a.ilungaTL226 Jun 2026#76
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physio_marchettiTL2Physiotherapist27 Jun 2026#77

Agreed on all of that, and I have nothing to add to it.

5 likes 1mo
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j.iyerTL227 Jun 2026#78

Detection at 214 nanometres sees the peptide bond and therefore sees almost everything peptidic. At 280 it sees aromatic residues, so a peptide without tryptophan or tyrosine will look very different or not appear at all.

14 likes 1mo
NR
n.rahimiTL227 Jun 2026#79

Practical experience of Carryover, offered as one case with the conditions stated, not as a general finding. Conditions first, because they are what make it interpretable.

15 likes 1mo
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l.dziedzicTL227 Jun 2026#80
i.ilunga, post #22: I would rather this thread reach "we do not know" about Carryover than reach a confident answer that nobody can support when asked. Go to post

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

30 likes in reply to #22 30d
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f.fontaineTL228 Jun 2026#81
physio_marchetti, post #77: Agreed on all of that, and I have nothing to add to it. Go to post

Typical suitability criteria are a replicate area relative standard deviation below about two per cent, a tailing factor inside a defined window, a resolution minimum against a specified peak, and a plate-count floor.

That is what the documentation says. What happens in practice is usually close.

24 likes in reply to #77 30d
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PSundbergTL2Member28 Jun 2026#82
a.molnar, post #59: Taking post #56 at face value and following it one step further. Carryover from a previous injection shows up as a small peak at the same retention time in a blank. A method report that includes a blank injection is telling you the analyst checked. I would not lead a decision with this, but I would not ignore it either. Go to post

A relative retention time against a known peak travels much better than an absolute one, and almost nobody reports it.

Marking that as an opinion rather than a finding.

11 likes in reply to #59 30d
YE
y.eriksenTL228 Jun 2026#83

Post #79 put the caveat in the right place and I want to underline it.

I have been on both sides of the Carryover argument in this category within eighteen months, which should tell you how strong the evidence for either side is.

1 like 30d
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sterile_tableTL3Regular28 Jun 2026#84

Carryover is a good example of a question where the honest answer is boring and the interesting answers are unsupported. I would go with boring.

0 likes 29d
CB
c.balogunTL229 Jun 2026#85
a.aguirre, post #5: Saving this. It is the version I will quote when the question comes round again. Go to post

Reversed-phase separates on hydrophobicity. A peptide is retained on a non-polar stationary phase and eluted by increasing organic solvent. For peptides the mobile phase almost always contains an ion-pairing acid, typically 0.1% TFA, which suppresses secondary interactions and sharpens peaks.

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

32 likes in reply to #5 29d
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LeitermanTL3Regular29 Jun 2026#86

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

16 likes 29d
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n.serranoTL229 Jun 2026#87
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r.marsdenTL3Regular29 Jun 2026 · edited#88

Adding a small correction to the Carryover summary above rather than a disagreement with it. The substance holds; one of the figures is out by a factor that matters.

0 likes 28d
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ni.stanescuTL230 Jun 2026#89

Post #88 describes the usual case. This is about the unusual one.

Column chemistry and particle size: smaller particles (1.7 μm) give better resolution and higher efficiency than larger particles (3.5 μm or 5 μm), at the cost of higher back pressure. Newer methods increasingly use smaller particles.

0 likes 28d
JH
j.habermannTL3Regular30 Jun 2026#90
sterile_table, post #84: Carryover is a good example of a question where the honest answer is boring and the interesting answers are unsupported. I would go with boring. Go to post

Careful with the language on Carryover. "Not detected" and "not present" are different findings and the first is a statement about the method.

23 likes in reply to #84 28d