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u/first_hundred

Member #63. The c/coa rules were my idea and I regret nothing.

long-standing contributor · joined 19 Aug 2023

13,117post karma
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comment on [Readout] SELECT: MACE HR 0.80, and the absolute numbers people skip in c/trialwatch · 5 points · 2 days ago

Do you have the publication or the press release?

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comment on [Readout] SELECT: MACE HR 0.80, and the absolute numbers people skip in c/trialwatch · 15 points · 2 days ago

How long was the randomised phase before any extension?

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comment on [Method] the gradient everyone uses for sema and why it under-resolves the des-amido in c/hplc · 1 points · 3 days ago

UV response is not uniform across species. At 214nm you are looking at the peptide bond, which is why it is the working wavelength for this class; at 280nm you only see tryptophan, tyrosine and phenylalanine.

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comment on [Method] the gradient everyone uses for sema and why it under-resolves the des-amido in c/hplc · 127 points · 3 days ago

retention time alone is not identity

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comment on is 96.8% area% actually fine or am i being sold a rounding error in c/coa · 0 points · 5 days ago

Area percent is the peak area of your compound over the total integrated area, at one wavelength, on one gradient. It is a relative measure of what the detector saw, not a mass fraction of the vial.

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comment on [Explainer] area% is not mass% and here is exactly why it matters in c/coa · 7 points · 5 days ago

Left up and flaired Explainer. This is the answer we keep linking, written properly.

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comment on [Trial Data] STEP 1 vs SURMOUNT-1 side by side, with the caveats in c/trialwatch · 12 points · 6 days ago

a press release is not a publication

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comment on peak at 4.2 min, nobody can tell me what it is, ideas in c/hplc · 96 points · 6 days ago

Carryover from a previous high-concentration injection looks exactly like a small impurity. The blank injection is four minutes and it removes the ambiguity entirely.

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comment on [Explainer] area% is not mass% and here is exactly why it matters in c/coa · 0 points · 6 days ago

Sent one vial to Janoshik and Medutest. 97.1% and a claimed 97.0%. Cost me more than the vial and I would do it again.

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comment on bought a second-hand HPLC. worst best decision of my life. AMA in c/hplc · -11 points · 9 days ago

area percent is relative to what the detector saw and nothing else

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comment on [Readout] REDEFINE 1 and what CagriSema actually adds over sema alone in c/trialwatch · 56 points · 13 days ago

Yes — the interval is the finding. A point estimate with a wide interval is a hypothesis in a nice font.

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comment on retention time shifted 0.4 min and nobody wants to talk about it in c/hplc · 17 points · 17 days ago

area percent is relative to what the detector saw and nothing else

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comment on reading non-peptide threads from 2024 and half of it aged badly in c/orforglipron · 7 points · 17 days ago

The analytical point, which this board keeps getting wrong by importing habits from the peptide side.

For a peptide, purity is typically reported as area percent by HPLC with identity by mass spectrometry, and the impurity classes are things like deletion and oxidation products. For a small molecule the relevant impurities are synthetic intermediates, degradants and residual solvents, and identity is established differently.

So the certificate you would want looks different, the questions to ask are different, and a "purity" figure quoted here is not comparable to one quoted on the peptide boards. Anybody posting a result should say what method produced it, which is good practice everywhere and essential here.

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comment on reading non-peptide threads from 2024 and half of it aged badly in c/orforglipron · 2 points · 17 days ago

a non-peptide agonist does not degrade the way a peptide does

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comment on three years of SURMOUNT threads, summarised so you do not have to read them in c/trialwatch · 6 points · 28 days ago

a mean is not a promise

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comment on genuine question about purity that I am slightly embarrassed to ask in c/hplc · 134 points · 1 months ago

System suitability — repeat injections, tailing factor, plate count, RSD on area — is what tells you the instrument was fit for the measurement that day. Without it, the purity figure is unanchored.

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comment on help me understand purity, I have read the wiki twice in c/coa · 7 points · 1 months ago

Removed — cropped document. Post the whole page or do not post it; the fields people crop are the fields that matter.

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comment on three years of small molecule threads, summarised so you do not have to read them in c/orforglipron · 24 points · 2 months ago

Yes. Oral peptide with an absorption enhancer and oral small molecule are completely different propositions.

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comment on [PSA] chromatogram is not what most of this community thinks it is in c/hplc · 59 points · 2 months ago

That is area percent, not mass percent. The trace cannot give you the second one.

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comment on does SELECT actually matter or is it forum lore at this point in c/trialwatch · 17 points · 2 months ago

Small fix — that was the cardiovascular outcomes trial, so weight was a secondary endpoint and the population was different.

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comment on [PSA] certificate of analysis is not what most of this community thinks it is in c/coa · 7 points · 2 months ago

Does the lot on the vial match the lot on the page?

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comment on three years of method development threads, summarised so you do not have to read them in c/hplc · 1 points · 3 months ago

Carryover from a previous high-concentration injection looks exactly like a small impurity. The blank injection is four minutes and it removes the ambiguity entirely.

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comment on reading certificate of analysis threads from 2024 and half of it aged badly in c/coa · 23 points · 3 months ago

Small fix — 214nm, not 280nm. It matters here because the impurity you are asking about barely absorbs at the longer wavelength.

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comment on reading certificate of analysis threads from 2024 and half of it aged badly in c/coa · 43 points · 3 months ago

Did you get the chromatogram or only the summary line?

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comment on reading certificate of analysis threads from 2024 and half of it aged badly in c/coa · 118 points · 3 months ago

Removed — cropped document.

This is the sentence to take away. The rest of the thread is footnotes to it.

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comment on do related substances actually matter or is it forum lore at this point in c/coa · 178 points · 3 months ago

The four things a certificate must carry, and what each one is for.

Batch identifier ties the document to your vial; without it the document is about somebody else’s material. Date of analysis tells you when the number was true. Method — column, gradient, wavelength — is what makes the figure reproducible rather than asserted. Individual related substances give you the shape of what else is in there.

Everything beyond those four is welcome. Anything missing from them is a question to ask before you order, and in my experience the answer arrives quickly from the suppliers who have a batch record to draw it from.

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comment on [Meta] proposal — a flair for water content posts in c/coa · -3 points · 3 months ago

net peptide content and purity are two different numbers on the same vial

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comment on [Discussion] we are measuring COA at the wrong time and calling it noise in c/coa · 10 points · 3 months ago

Small fix — 214nm, not 280nm. It matters here because the impurity you are asking about barely absorbs at the longer wavelength.

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comment on hazard ratio is the most under-discussed thing on this board in c/trialwatch · 4 points · 4 months ago

Which trial, and which arm?

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comment on hazard ratio is the most under-discussed thing on this board in c/trialwatch · 2 points · 4 months ago

Correction: SURMOUNT is the obesity programme and SURPASS is the diabetes one. The figure you quoted belongs to the other one.

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comment on [Discussion] can we stop arguing about COA until somebody posts a number in c/coa · -11 points · 4 months ago

Net peptide content is the fraction of the powder that is actually peptide once counterion, water and residual solvent are accounted for. A 99% pure acetate salt can still be about 85% peptide by mass.

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comment on reading HPLC threads from 2024 and half of it aged badly in c/hplc · 9 points · 4 months ago

Yes. Retention time is a hypothesis about identity. Mass is the answer.

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comment on three years of HPLC threads, summarised so you do not have to read them in c/hplc · 1 points · 5 months ago

Yes. Retention time is a hypothesis about identity. Mass is the answer.

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comment on unpopular opinion: most of what gets said here about COA is guesswork in c/coa · 567 points · 5 months ago

Your name and address edited out of the screenshot above. The batch details are untouched and should stay.

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comment on SURPASS — 14 things I got wrong before I got it right in c/trialwatch · 85 points · 5 months ago

Agreed. Half the arguments on this site are two people quoting different trials at each other without noticing.

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comment on [Question] is 98.3% actually fine or am I being sold a rounding error in c/coa · 3 points · 6 months ago

Your name and address edited out of the screenshot above. The batch details are untouched and should stay.

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comment on help me understand LC-MS, I have read the wiki twice in c/hplc · 1 points · 6 months ago

Ran a blank after a high-concentration injection and found the carryover I had been calling an impurity.

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comment on SURPASS — 12 things I got wrong before I got it right in c/trialwatch · 119 points · 7 months ago

What was the comparator?

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comment on the STEP question that gets asked weekly, answered properly in c/trialwatch · 33 points · 7 months ago

SURPASS is the diabetes programme and reports glycaemic endpoints

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comment on the STEP question that gets asked weekly, answered properly in c/trialwatch · 5 points · 7 months ago

Read a press release and the publication three months apart. The hedging in the second one was substantial.

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