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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.yilmazTL2 Moderator24 Apr 2025#61

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.

16 likes 15mo
GI
g.ibarraTL2 Moderator25 Apr 2025#62

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.

31 likes 15mo
SC
s.cardosoTL2 Moderator26 Apr 2025#63
r.venkatesan, post #56: post #55 answers the question as asked. The question underneath it is different. 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. Go to post

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

Tandem mass spectrometry: MS/MS fragments the molecular ion and uses fragment masses to confirm identity and detect modifications. A simple identity confirmation by LC-MS does not address post-translational modifications or impurities with the same or very close mass.

0 likes in reply to #56 15mo
JD
j.dahlbergTL2 Moderator28 Apr 2025 · edited#64
a.cardoso, post #8: 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. Go to post

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.

3 likes in reply to #8 15mo
TW
t.wojcikTL2 Moderator29 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.kowalskiTL2 Moderator30 Apr 2025#66

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.

0 likes 15mo
EP
e.piresTL2 Moderator1 May 2025#67
logbook_erin, post #52: 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. Go to post

This follows post #64 rather than contradicting it.

Purity and identity are different questions: LC-MS establishes that the species at a retention time has the expected mass. It does not establish how much of the sample is that species (that is what LC-UV purity answers).

1 like in reply to #52 15mo
SK
s.kimaniTL2 Moderator2 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

I read post #66 twice before replying, because I had assumed the opposite.

Two things before anyone answers the substance.

First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.

6 likes in reply to #1 15mo
IO
i.oseiTL2 Moderator3 May 2025#69

post #68 answers the question as asked. The question underneath it is different.

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.

30 likes 15mo
O
OkaforTL3Regular4 May 2025#70

On post #66 — agreed on the reasoning, with one qualification.

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.

0 likes 15mo
JW
journalclub_wrenTL3Regular6 May 2025#71
j.habermann, post #22: Worth separating two things that post #18 runs together. Purity and identity are different questions: LC-MS establishes that the species at a retention time has the expected mass. It does not establish how much of the sample is that species (that is what LC-UV purity answers). Go to post

What mass accuracy establishes: the measured mass is consistent with a specific composition. What it does not establish: purity, sequence order, stereochemistry, or the absence of an isobaric species. Every one of those requires something else.

10 likes in reply to #22 15mo
RF
ro.friskTL2 Moderator7 May 2025 · edited#72

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.

3 likes 15mo
DS
dr_seongTL3Physician8 May 2025#73

Worth separating two things that post #69 runs together.

Common adducts: sodium adds ≈22, potassium adds ≈38 compared to hydrogen. A [M+Na]+ peak is common and its mass is predictable from the base mass.

0 likes 15mo
PM
p.mwangiTL2 Moderator9 May 2025#74
d.achebe, post #47: 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. Go to post

post #73 is right about the mechanism and I think understates the practical bit.

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.

30 likes in reply to #47 15mo
ST
slow_titratorTL2Regular10 May 2025#75
two_year_line, post #16: post #15 is right about the mechanism and I think understates the practical bit. 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. Go to post

Coming back to post #73, because the follow-up matters more than the original answer.

Common adducts: sodium adds ≈22, potassium adds ≈38 compared to hydrogen. A [M+Na]+ peak is common and its mass is predictable from the base mass.

15 likes in reply to #16 15mo
TK
t.karlsenTL2 Moderator11 May 2025#76

For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.

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

What mass accuracy establishes: the measured mass is consistent with a specific composition. What it does not establish: purity, sequence order, stereochemistry, or the absence of an isobaric species. Every one of those requires something else.

0 likes 15mo
YA
y.asanteTL2 Moderator13 May 2025#78

post #77 answers the question as asked. The question underneath it is different.

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.

0 likes 14mo
DO
dr_okonkwoTL4 Moderator15 May 2025 · edited#79
Staff post. Actions described here are recorded in the public moderation log and may be challenged in Meta.

I read post #77 twice before replying, because I had assumed the opposite.

Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive.

21 likes 14mo
CG
c.grimaldiTL2 Moderator16 May 2025#80

This follows post #77 rather than contradicting it.

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.

9 likes 14mo
HF
h.falkTL2 Moderator17 May 2025 · edited#81

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.

28 likes 14mo
TD
titration_diaryTL3Regular18 May 2025#82
p.krastev, post #55: Two things before anyone answers the substance. First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound. Go to post

Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive.

0 likes in reply to #55 14mo
TD
t.duarteTL2 Moderator19 May 2025#83

post #82 answers the question as asked. The question underneath it is different.

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 14mo
EF
e.ferreiraTL3Regular20 May 2025#84

On post #80 — agreed on the reasoning, with one qualification.

Tandem mass spectrometry: MS/MS fragments the molecular ion and uses fragment masses to confirm identity and detect modifications. A simple identity confirmation by LC-MS does not address post-translational modifications or impurities with the same or very close mass.

14 likes 14mo
SZ
s.zamoraTL2 Moderator21 May 2025 · edited#85

Purity and identity are different questions: LC-MS establishes that the species at a retention time has the expected mass. It does not establish how much of the sample is that species (that is what LC-UV purity answers).

21 likes 14mo
DS
d.szymanskiTL3Wiki editor22 May 2025#86
e.pires, post #67: This follows post #64 rather than contradicting it. Purity and identity are different questions: LC-MS establishes that the species at a retention time has the expected mass. It does not establish how much of the sample is that species (that is what LC-UV purity answers). Go to post

I read post #84 twice before replying, because I had assumed the opposite.

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.

0 likes in reply to #67 14mo
IG
i.guerreroTL2 Moderator23 May 2025#87
e.nilsen, post #10: Coming back to post #8, because the follow-up matters more than the original answer. 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… Go to post

post #86 is right about the mechanism and I think understates the practical bit.

For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.

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

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 14mo
EF
e.ferreiraTL3Regular26 May 2025#89
j.habermann, post #22: Worth separating two things that post #18 runs together. Purity and identity are different questions: LC-MS establishes that the species at a retention time has the expected mass. It does not establish how much of the sample is that species (that is what LC-UV purity answers). Go to post

Picking up post #86: that is the part I would want checked first.

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.

14 likes in reply to #22 14mo
CW
c.wijnbergTL2Member27 May 2025#90

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.

29 likes 14mo