The Peptide CommonsEst. May 2024
Independent. We sell nothing and are affiliated with no manufacturer or pharmacy. Every moderation action is logged in public
Analytics · Mass spectrometry · continued

Charge states for a 4 kDa peptide, worked through 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.

GT
g.tanakaTL3Regular9 Mar 2025#61

This follows post #60 rather than contradicting it.

Charge states sits at the boundary between what this community can usefully discuss and what it cannot, and I think it falls on the discussable side, narrowly.

1 like 17mo
MM
m.mwangiTL29 Mar 2025#62

Mass accuracy is expressed in parts per million. It is the difference between observed and theoretical mass divided by theoretical mass, multiplied by a million. A high-resolution instrument in good calibration achieves low single-digit ppm on a peptide of this size.

The general answer and the answer for your case may diverge here.

6 likes 17mo
DS
d.szymanskiTL3Wiki editor10 Mar 2025#63

An honest declaration on charge states: I have a prior here and it is strong enough that you should weight what I say downward. Stating it rather than hiding it.

16 likes 17mo
EN
e.ndiayeTL210 Mar 2025 · edited#64
c.correia, post #20: Building on post #19 rather than restating it. 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. Go to post

Coming back to post #62, because the follow-up matters more than the original answer.

Charge states is worth one more sentence than it usually gets, and the sentence is the one about how the number was arrived at.

31 likes in reply to #20 17mo
K
KAnderssonTL3Regular10 Mar 2025#65
o.nyberg, post #35: Everything in post #33 holds. The case it does not cover is the one I have. I would rather this thread reach "we do not know" about charge states than reach a confident answer that nobody can support when asked. Go to post

Taking post #64 at face value and following it one step further.

The arithmetic for a doubly charged species is (M + 2 x 1.00728) / 2, and the analogous expression for higher charge states. Working it through once makes the reported values legible.

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

3 likes in reply to #35 17mo
EF
e.ferreiraTL3Regular10 Mar 2025#66

Post #62 and I disagree about the size of the effect, not about the direction.

What I would tell a new member reading about charge states for the first time: the confident posts are not the reliable ones, and the reliable ones are longer.

10 likes 17mo
H
HHidalgoTL2Member10 Mar 2025#67

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

22 likes 17mo
SD
st.dialloTL210 Mar 2025#68
j.delacroix, post #14: Seconded. It reads as careful rather than confident, which is the right register. Go to post

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.

0 likes in reply to #14 17mo
BS
buffer_shiftTL1Member10 Mar 2025#69

I think the charge states question is answerable and has not been answered, which is a more optimistic position than most of this thread.

0 likes 17mo
BC
b.correiaTL210 Mar 2025#70
MR
m.ramosTL210 Mar 2025#71
Makinen, post #36: An acylated peptide has a mass that reflects the modification, so comparing against the mass of the unmodified backbone gives a mismatch that is not an error. Go to post

Post #69 put the caveat in the right place and I want to underline it.

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.

The evidence for this is thinner than the way I have phrased it suggests.

0 likes in reply to #36 17mo
CB
careful_beginnerTL1Member11 Mar 2025 · edited#72
cannula_trace, post #21: Charge states observed: for semaglutide (4113.6 Da) the doubly charged ion appears at m/z ≈ 2057, triply charged at ≈ 1371, quadruply at ≈ 1029. Those are the positions to look for; the heights depend on the ionization efficiency. Go to post

Building on post #69 rather than restating it.

An acylated peptide has a mass that reflects the modification, so comparing against the mass of the unmodified backbone gives a mismatch that is not an error.

On reflection I would soften that slightly.

30 likes in reply to #21 17mo
MI
m.ilungaTL211 Mar 2025#73

On charge states: the maintained page in the documentation commons covers the general case with citations and a review date, which is more reliable than any reply here including this one.

15 likes 17mo
RH
revision_historyTL3Wiki editor11 Mar 2025#74

I would put moderate confidence on the mainstream reading of charge states and no more. That is not scepticism for its own sake; it is where the sourcing actually stops.

5 likes 17mo
AL
a.lindqvistTL211 Mar 2025#75

Second this, and I would have said it less carefully.

0 likes 17mo
GV
g.valckenaereTL3Regular11 Mar 2025#76
j.delacroix, post #14: Seconded. It reads as careful rather than confident, which is the right register. Go to post

Taking post #73 at face value and following it one step further.

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 interesting part of this is the exception, and I do not understand the exception.

0 likes in reply to #14 17mo
SR
s.roosTL211 Mar 2025#77

Desalting before analysis: some samples need desalting to remove salts that suppress the peptide signal. Report whether desalting was used, because it can affect the apparent ionization efficiency and the reported purity.

Worth one more sentence than it usually gets.

21 likes 17mo
DN
desiccant_notesTL2Member11 Mar 2025#78

Sample matrix effects: if a sample is dissolved in a complex matrix, other compounds in the matrix can suppress the peptide signal. Clean samples give higher sensitivity than dirty samples.

9 likes 17mo
GE
g.ekstromTL211 Mar 2025#79

The reason charge states keeps being re-asked is that the answer is conditional and people quote it without the condition. It is not that the answer is unknown.

31 likes 17mo
L
LeitermanTL3Regular11 Mar 2025#80
p.diallo, post #6: Post #4 describes the usual case. This is about the unusual one. Charge states looks different depending on whether you are reading the primary literature or the summaries of it, and the difference is not in our favour. Go to post

Reading back through the charge states threads from last year, the same three questions come up every time and only one of them has ever been answered properly. That seems like a documentation gap rather than a knowledge gap.

15 likes in reply to #6 17mo
EA
e.adeyemiTL212 Mar 2025#81

Narrowing post #78, because the general version has more than one answer.

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.

That holds under the stated conditions and I have stated them.

0 likes 17mo
GT
g.tanakaTL3Regular12 Mar 2025#82

Everything in post #80 holds. The case it does not cover is the one I have.

Distinguishing three things in the charge states discussion that keep getting used interchangeably: the observation, the proposed mechanism, and the recommendation that gets attached to both.

0 likes 17mo
AJ
a.jansenTL212 Mar 2025 · edited#83
se.okafor, post #26: Worth separating two things that post #22 runs together. Calibration state at the time of the run determines whether the ppm figure means anything. A report that states when the instrument was last calibrated is unusual and is worth more than one that does not. That is what I would do. It may not be what is correct. Go to post

Electrospray ionisation produces multiply charged ions. For a 4 kDa peptide you expect mostly 2+, 3+, and 4+ charge states. Reading an electrospray spectrum means recognizing the envelope, not looking for one peak.

The general case is well covered; this is the awkward specific one.

9 likes in reply to #26 17mo
PR
policy_readerTL2Regular12 Mar 2025#84
b.adeyemi, post #45: This follows post #42 rather than contradicting it. Reading this charge states thread as someone who came in with a fixed view: the third and seventh replies moved me and the confident ones did not. Go to post

Trifluoroacetate adducts are common in material purified with TFA and are one reason a mass spectrum from a peptide can look busier than expected.

20 likes in reply to #45 17mo
EN
e.ndiayeTL212 Mar 2025#85

Adding a note of thanks rather than an opinion. I did not know most of that.

29 likes 17mo
K
KAnderssonTL3Regular12 Mar 2025#86

The strongest argument against my own position on charge states, stated as well as I can state it, since nobody else has yet.

0 likes 17mo
MM
m.mwangiTL212 Mar 2025#87

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.

5 likes 17mo
DS
d.szymanskiTL312 Mar 2025#88
RZ
r.zielinskiTL212 Mar 2025#89

The practical version of charge states is three sentences long. The rigorous version is three pages and reaches the same conclusion with the conditions attached.

0 likes 17mo
PP
peak_purityTL3Analytical chemist13 Mar 2025#90

Calibration state at the time of the run determines whether the ppm figure means anything. A report that states when the instrument was last calibrated is unusual and is worth more than one that does not.

5 likes 17mo