Analytics · Mass spectrometry · continued

High-resolution MS on aggregates and what it can see posts 61–90

Analytics › Mass spectrometry charge states counter-ion content high-resolution MS

This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.

BDraganovTL2Member6 Sep 2025#61

n.nyberg, post #43: Building on post #40 rather than restating it. Answering the high-resolution 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. Go to post

Quantitation by MS: most quantitation is done by LC-UV detection at 214 nm, not by MS, because extinction coefficients are better known. MS can quantify if an internal standard is used but that requires preparation.

I would hold that lightly until someone with a larger sample weighs in.

12 likes in reply to #43 11mo

h.kimaniTL27 Sep 2025#62

l.ibarra, post #57: I read post #53 twice before replying, because I had assumed the opposite. The strongest argument against my own position on high-resolution, stated as well as I can state it, since nobody else has yet. Go to post

Noted, and thank you for writing it out rather than summarising it.

25 likes in reply to #57 11mo

h.almeidaTL2Member8 Sep 2025#63

Post #61 answers the question as asked. The question underneath it is different.

What I want from this high-resolution 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.

0 likes 11mo

j.palaciosTL210 Sep 2025#64

Resolution and mass accuracy are different specifications. An instrument can resolve two species and still assign their masses imprecisely, and the reverse is also possible.

That is the practical version. The rigorous version is longer and says the same thing.

4 likes 11mo

t.kulkarniTL3Regular11 Sep 2025#65

g.ekstrom, post #39: Resolution and mass accuracy are different specifications. An instrument can resolve two species and still assign their masses imprecisely, and the reverse is also possible. Go to post

The thing about high-resolution that took me longest to accept is that a plausible mechanism is not evidence of an effect. It is a reason to look, not a result.

8 likes in reply to #39 11mo

p.novakTL212 Sep 2025 · edited#66

j.vogel, post #54: High-resolution is worth one more sentence than it usually gets, and the sentence is the one about how the number was arrived at. Go to post

Posting my high-resolution numbers with the method attached so they can be discounted properly. Uncontrolled, unblinded, and collected by someone who wanted a particular answer.

18 likes in reply to #54 10mo

r.jhannsdttirTL3Regular13 Sep 2025#67

Narrowing post #66, because the general version has more than one answer.

The honest summary of what a mass result buys you: it narrows the field of what the material could be, considerably. It never closes it, and no certificate should be read as though it had.

0 likes 10mo

a.vermeulenTL215 Sep 2025#68

Everything in post #64 holds. The case it does not cover is the one I have.

An update on my earlier high-resolution post: the pattern held for another six weeks and then stopped, which I did not predict and cannot explain.

2 likes 10mo

v.milanoviTL3Regular16 Sep 2025#69

h.almeida, post #63: Post #61 answers the question as asked. The question underneath it is different. What I want from this high-resolution 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. Go to post

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

4 likes in reply to #63 10mo

ne.laurentTL217 Sep 2025#70

Resolution: "high resolution" commonly means <5 ppm across the mass range. Unit-resolution instruments achieve ±1 Da at best and cannot distinguish two species differing by less than 1 Da in total mass.

The short version is the first sentence; the rest is why.

13 likes 10mo

s.silvaTL218 Sep 2025#71

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

I read the earlier replies on high-resolution 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.

23 likes 10mo

e.kimaniTL220 Sep 2025#72

The honest answer on high-resolution 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.

11 likes 10mo

a.weissTL221 Sep 2025 · edited#73

Positional isomers and epimers are mass-identical. Any argument that a mass result rules them out is wrong, and it is the commonest overclaim in this subcategory.

The uncertainty is in the assumption, not in the calculation.

1 like 10mo

e.ferrariTL222 Sep 2025#74

s.roos, post #33: Resolution: "high resolution" commonly means Go to post

Reporting rather than recommending, on high-resolution. What happened is above. Whether it should have is a different question and not one I am qualified to answer.

0 likes in reply to #33 10mo

l.dziedzicTL223 Sep 2025#75

My position on high-resolution is current rather than settled. I have revised it once already and I expect to again, so treat it accordingly.

31 likes 10mo

k.roosTL224 Sep 2025#76

Collapsed as off-topic by two members at trust level 3 or above

Not the answer, but possibly the question that gets there.

a.ibarraTL226 Sep 2025#77

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

3 likes 10mo

n.lehtinenTL227 Sep 2025#78

The arithmetic in post #75 is right; the assumption feeding it is the part to check.

High-resolution 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.

0 likes in reply to #43 10mo

s.poulsenTL3Regular28 Sep 2025#79

desiccant_notes, post #34: Thank you for taking the time. That was more work than a reply usually is. Go to post

The honest summary of what a mass result buys you: it narrows the field of what the material could be, considerably. It never closes it, and no certificate should be read as though it had.

Posting it because the silence on this was starting to look like agreement.

11 likes in reply to #34 10mo

e.tammTL229 Sep 2025#80

Confirming post #79 from a second method, which matters more than confirming it from a second person.

If you are new and reading this thread for the answer to high-resolution: the answer is conditional, the conditions are in the third reply, and the rest of the thread is worth skipping.

3 likes 10mo

h.iyerTL230 Sep 2025#81

Collapsed as off-topic by two members at trust level 3 or above

Confirming post #80 from a second method, which matters more than confirming it from a second person.

On high-resolution I would separate what is worth knowing from what is worth acting on. The first list is long and the second is short, and conflating them is how threads get heated.

blank_injectionTL2Analytical chemist2 Oct 2025#82

formulary_notes, post #15: Speaking only to high-resolution 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

I had written a reply contradicting post #78 and deleted it. Here is what survived.

Resolution and mass accuracy are different specifications. An instrument can resolve two species and still assign their masses imprecisely, and the reverse is also possible.

14 likes in reply to #15 10mo

n.villalobosTL23 Oct 2025#83

The most useful reply I ever got about high-resolution was a request to state my units. It sounds like pedantry and it has saved me twice.

29 likes 10mo

forest_plotTL3Evidence synthesis4 Oct 2025#84

Take it as a starting point and not as a specification.

0 likes 10mo

f.amankwahTL25 Oct 2025#85

s.roos, post #33: Resolution: "high resolution" commonly means Go to post

Post #84 is right about the mechanism and I think understates the practical bit.

A note on how high-resolution gets discussed rather than on high-resolution itself: the confident posts get the replies and the careful ones get ignored, and the careful ones have been right more often.

9 likes in reply to #33 10mo

hana.satoTL4 Moderator6 Oct 2025#86

Worth stating the null on high-resolution before we explain it: the observation may be nothing. That possibility deserves a sentence and usually does not get one.

20 likes 10mo

n.okwuosaTL28 Oct 2025 · edited#87

The honest summary of what a mass result buys you: it narrows the field of what the material could be, considerably. It never closes it, and no certificate should be read as though it had.

Worth saying I have only my own numbers here, and n is small.

0 likes 10mo

p.iyer_pharmdTL3Pharmacist9 Oct 2025#88

On post #86 — agreed on the reasoning, with one qualification.

Mass error in parts per million is (observed minus theoretical) divided by theoretical, times a million. On a high-resolution instrument a low single-digit figure is unremarkable and expected.

I keep a log of this specifically because memory is unreliable about it.

0 likes 10mo

z.cardosoTL210 Oct 2025#89

r.jhannsdttir, post #67: Narrowing post #66, because the general version has more than one answer. The honest summary of what a mass result buys you: it narrows the field of what the material could be, considerably. It never closes it, and no certificate should be read as though it had. Go to post

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

13 likes in reply to #67 10mo

p.novotnyTL2Regular11 Oct 2025#90

I would call the community position on high-resolution likely rather than established, and I would be comfortable defending that hedge.

28 likes 10mo