Where two documents for the same lot disagree, the useful question is which was measured and which was transcribed. Most such disagreements are the second.
A modest claim, modestly supported.
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Analytics · COA interpretation · continued
Second pass at: A field-by-field walk through a certificate of analysis 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.
Field-by-field walk through a certificate: 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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Taking post #90 at face value and following it one step further.
An itemised related-substances table with retention times says considerably more about the synthesis than a single total. A total tells you how much is not the main peak and nothing about what it is.
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k.bettencourt, post #47: I read post #43 twice before replying, because I had assumed the opposite. I have no financial interest in anything named in this thread and I want to say so before I comment on field-by-field walk through a certificate, because it is the sort of subject where it matters. Go to post
Two questions I would want answered before drawing anything from the field-by-field walk through a certificate data above: how were the cases selected, and what happened to the ones that dropped out.
When method identifiers are missing: "reversed-phase HPLC" is less specific than "reversed-phase HPLC at 214 nm on a C18 column with a 10 to 40% acetonitrile gradient over 20 minutes". The second lets someone reproduce the analysis. The first does not.
It is the sort of thing that seems obvious in retrospect and was not at the time.
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Collapsed as off-topic by two members at trust level 3 or above
Reading old certificates: if a certificate is dated years ago, the lot it describes might be old. That is not automatically a problem but it is worth noting. Fresh testing on the current lot is stronger than old testing on an older lot.
That has been true for the cases I have seen and I have not seen many.
a.reyes, post #17: The distinction between release testing and characterisation is one industrial documents make and retail ones usually do not. It is the difference between "we tested every lot for this" and "we established this once". I would want a second opinion before relying on that. Go to post
This follows post #94 rather than contradicting it.
What I want from this field-by-field walk through a certificate 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.
t.nardone, post #39: "Not less than 98 per cent" is a specification. "98.3 per cent" is a result. A certificate carrying only the first has not told you what was measured. I would hold that lightly until someone with a larger sample weighs in. Go to post
Noted, and I have changed what I was going to do on the strength of it.
c.nyberg, post #4: An itemised related-substances table with retention times says considerably more about the synthesis than a single total. A total tells you how much is not the main peak and nothing about what it is. Go to post
Post #97 is right about the mechanism and I think understates the practical bit.
Small methodological point on field-by-field walk through a certificate: repeating a measurement is cheap and resolves most of what is being argued about here at no cost to anyone.
Coming back to post #97, because the follow-up matters more than the original answer.
When a document puts the specification in the result column, it has told you the release criterion, not the measurement. Those are different claims and the second is weaker.
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s.poulsen, post #26: Fair, and the limits you put on it are the part I will remember. Go to post
Reading rather than answering, but this is the post I would point somebody at.
Collapsed as off-topic by two members at trust level 3 or above
Answering the question post #99 raises rather than the one it answers.
Peptide content and chromatographic purity are separate determinations and a certificate that reports only one has answered only one question. Content is the one that tells you how much is in the vial.
That is what I would do. It may not be what is correct.
Two claims get bundled together under field-by-field walk through a certificate and they need separating. The descriptive one — this is what was observed — is usually well supported. The causal one — this is why — usually is not.
Almost every disagreement in threads like this one dissolves once you say which of the two you are making.
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b.osei, post #16: Worth separating two things that post #13 runs together. A note on scope: what I am saying about field-by-field walk through a certificate applies to the case in the first post and I would not extend it further without checking. Go to post
The distinction between release testing and characterisation is one industrial documents make and retail ones usually do not. It is the difference between "we tested every lot for this" and "we established this once".
An itemised related-substances table with retention times says considerably more about the synthesis than a single total. A total tells you how much is not the main peak and nothing about what it is.
The honest answer is that it depends, and here is what it depends on.
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Post #104 is the version of this I will quote in future. One addition.
What fields matter on a certificate: lot number matching the vial, test date, the analytical method stated specifically, the measured result as a number, and the acceptance limit stated separately. A certificate missing any of these is weaker.
That has held every time I have looked, which is not the same as always.
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Where I part company with post #106, and it is a narrow parting.
Endotoxin testing is separate: a certificate of purity says nothing about endotoxin. A chemically pure preparation can carry a clinically significant endotoxin load. If endotoxin matters, it needs to be tested and reported.
Anyone who has looked at this more carefully, please correct the record.
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j.habermann, post #30: Where two documents for the same lot disagree, the useful question is which was measured and which was transcribed. Most such disagreements are the second. Go to post
I changed my mind about field-by-field walk through a certificate after someone here asked me for the source and I could not produce one. That is worth saying out loud because it is the ordinary way it happens.
i.broberg, post #65: Endotoxin testing is separate: a certificate of purity says nothing about endotoxin. A chemically pure preparation can carry a clinically significant endotoxin load. If endotoxin matters, it needs to be tested and reported. I would rather post the uncertainty than round it away. Go to post
Amino acid analysis gives content: it hydrolyses the peptide and quantifies the residues. It measures the peptide content independent of chromatographic purity. Very few supplier certificates report it.
An itemised related-substances table with retention times says considerably more about the synthesis than a single total. A total tells you how much is not the main peak and nothing about what it is.
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v.rautio, post #54: I had written a reply contradicting post #52 and deleted it. Here is what survived. Asking for the batch record rather than the certificate is a reasonable request and the response to it is informative whichever way it goes. If anyone has run this properly I would rather read that than my own guess. Go to post
Building on post #116 rather than restating it.
When method identifiers are missing: "reversed-phase HPLC" is less specific than "reversed-phase HPLC at 214 nm on a C18 column with a 10 to 40% acetonitrile gradient over 20 minutes". The second lets someone reproduce the analysis. The first does not.
That holds for the case as described. Change the assumptions and it may not.
n.cabrera, post #83: Asking for the batch record rather than the certificate is a reasonable request and the response to it is informative whichever way it goes. That much is documented. The rest is how I have interpreted it. Go to post
Reading rather than contributing, but this is the most useful thread I have found on it.