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

Reading an MS report that only gives you a single number posts 61–90

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

MY
m.yilmazTL224 Apr 2025#61

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.

16 likes 15mo
GI
g.ibarraTL225 Apr 2025#62

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 rule of thumb is fine; the edge cases are where it earns its keep.

31 likes 15mo
SC
s.cardosoTL226 Apr 2025#63
r.venkatesan, post #56: Confirming post #55 from a second method, which matters more than confirming it from a second person. 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. Anyone with a larger… Go to post

Picking up post #60: that is the part I would want checked first.

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.

A qualification I should have led with rather than closed on.

0 likes in reply to #56 15mo
JD
j.dahlbergTL228 Apr 2025 · edited#64
a.cardoso, post #8: 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

Adducts — sodium and potassium especially — shift the observed mass in predictable increments. A report showing an unexplained plus twenty-two is usually showing you a sodium adduct.

3 likes in reply to #8 15mo
TW
t.wojcikTL229 Apr 2025#65

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.

22 likes 15mo
AK
a.kowalskiTL230 Apr 2025#66

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 15mo
EP
e.piresTL21 May 2025#67
logbook_erin, post #52: 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. Stating my assumptions rather than smuggling them in. Go to post

This follows post #64 rather than contradicting it.

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.

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

1 like in reply to #52 15mo
SK
s.kimaniTL22 May 2025#68
b.demir, post #1: On the subject in the title: Reading an MS report that only gives you a single number Working notes rather than a conclusion. I would like to understand what this number means before I repeat it anywhere. A VendorInvestigate report on a tirzepatide lot gives 97.1% purity. The supplier certificate for the same lot states 97.6%. Both… Go to post

Worth separating two things that post #66 runs together.

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.

A modest claim, modestly supported.

6 likes in reply to #1 15mo
IO
i.oseiTL23 May 2025#69

Narrowing post #68, because the general version has more than one answer.

Tandem mass spectrometry with fragmentation gives sequence information that intact mass cannot. It is the analysis that would actually confirm identity, and it is rarely supplied.

Old habit: I write down the expected answer before I calculate it.

30 likes 15mo
O
OkaforTL3Regular4 May 2025#70

That matches what I have seen, for whatever a single anecdote is worth.

0 likes 15mo
JW
journalclub_wrenTL3Regular6 May 2025#71
j.habermann, post #22: Coming back to post #18, because the follow-up matters more than the original answer. Electrospray on a peptide of this size gives a multiply charged series rather than a single ion. Seeing only one charge state usually means the deconvolution has already been done for you, which is worth knowing. 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.

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

10 likes in reply to #22 15mo
RF
ro.friskTL27 May 2025 · edited#72

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.

3 likes 15mo
DS
dr_seongTL3Physician8 May 2025#73

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

Not a strong opinion, just a consistent one.

0 likes 15mo
PM
p.mwangiTL29 May 2025#74
d.achebe, post #47: Resolution: "high resolution" commonly means Small point, but it is the one that usually catches people. Go to post

Building on post #73 rather than restating it.

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.

If anyone has run this properly I would rather read that than my own guess.

30 likes in reply to #47 15mo
ST
slow_titratorTL2Regular10 May 2025#75
two_year_line, post #16: Adding the measurement that post #15 says would settle it. 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. The reasoning is more useful than the number, which is why I have shown it. Go to post

I read post #73 twice before replying, because I had assumed the opposite.

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.

Not a conclusion. A place to stand while looking for one.

15 likes in reply to #16 15mo
TK
t.karlsenTL211 May 2025#76

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.

I have written this out at length because the short version keeps being misread.

5 likes 15mo
WN
w.novakTL3Regular12 May 2025#77

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 15mo
YA
y.asanteTL213 May 2025#78

Taking post #77 at face value and following it one step further.

Calibration matters: a high-resolution instrument out of calibration can report mass with ppm error large enough to be uninformative. Check when the instrument was last calibrated before trusting the reported accuracy.

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

0 likes 14mo
DO
dr_okonkwoTL4 Moderator15 May 2025 · edited#79

Post #77 describes the usual case. This is about the unusual one.

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.

21 likes 14mo
CG
c.grimaldiTL216 May 2025#80

Reading rather than contributing, but this is the most useful thread I have found on it.

9 likes 14mo
HF
h.falkTL217 May 2025 · edited#81

Electrospray on a peptide of this size gives a multiply charged series rather than a single ion. Seeing only one charge state usually means the deconvolution has already been done for you, which is worth knowing.

I would want the raw data before agreeing with my own summary of it.

28 likes 14mo
TD
titration_diaryTL3Regular18 May 2025#82
p.krastev, post #55: 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. This is where my knowledge stops and I would rather mark the edge than blur it. Go to post

Adducts — sodium and potassium especially — shift the observed mass in predictable increments. A report showing an unexplained plus twenty-two is usually showing you a sodium adduct.

0 likes in reply to #55 14mo
TD
t.duarteTL219 May 2025#83

The arithmetic in post #82 is right; the assumption feeding it is the part to check.

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.

5 likes 14mo
EF
e.ferreiraTL3Regular20 May 2025#84

Answering the question post #81 raises rather than the one it answers.

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.

One more caveat and then I will stop qualifying: the sample selected itself.

14 likes 14mo
SZ
s.zamoraTL221 May 2025 · edited#85

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.

21 likes 14mo
DS
d.szymanskiTL3Wiki editor22 May 2025#86
e.pires, post #67: This follows post #64 rather than contradicting it. 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. Written from notes rather than memory, which is why the numbers are specific. Go to post

Where I part company with post #84, and it is a narrow parting.

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.

0 likes in reply to #67 14mo
IG
i.guerreroTL223 May 2025#87
e.nilsen, post #10: Answering the question post #8 raises rather than the one it answers. Resolution: "high resolution" commonly means Filing this under things that are true until someone shows me otherwise. Go to post

Adding the measurement that post #86 says would settle 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.

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

2 likes in reply to #10 14mo
BW
bac_waterTL2Regular24 May 2025#88

Thank you for taking the time. That was more work than a reply usually is.

9 likes 14mo
EF
e.ferreiraTL3Regular26 May 2025#89
j.habermann, post #22: Coming back to post #18, because the follow-up matters more than the original answer. Electrospray on a peptide of this size gives a multiply charged series rather than a single ion. Seeing only one charge state usually means the deconvolution has already been done for you, which is worth knowing. Go to post

This follows post #86 rather than contradicting it.

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 #22 14mo
CW
c.wijnbergTL2Member27 May 2025#90

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.

Correct me on the arithmetic if it is wrong; I would rather know.

29 likes 14mo