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c/hplc·posted 2 years ago by u/hana_lehtinen

chromatogram is the most under-discussed thing on this board

Correction Well Actually ×5 Clean Column ×3 Long Haul ×3

chromatogram is the most under-discussed thing on this board. I have gone back and forth on this for months.

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.

Area percent is the integrated area of your peak over the total integrated area at one wavelength on one gradient. Change any of those and the number changes without the sample changing.

Resolution between two peaks depends on retention, selectivity and efficiency. A shallower gradient buys retention and usually resolution, at the cost of peak width and run time.

That is everything I have. The rest is opinion and I have tried to keep it out.

4,455 up / 1,101 down80% upvoted55 commentsid 1p4rcg11 Jan 2024

55 comments

30 in this archive, depth 5

best — the order this archive was captured in

u/marisol_frisk309 points·2 years ago

Mass spectrometry answers identity. UV purity answers relative quantity under the run conditions. A document with one and not the other is answering half the question, and the half it answers should be stated.

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u/mass_spec_maggieMOD247 points·2 years ago

Method questions stay here; supplier claims go to c/vendorvetting with a document attached.

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u/hana_lehtinenOP132 points·2 years ago

Small fix — 214nm, not 210. It matters for the comparison you are making with the other run.

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u/niels_lindqvist-5 points·2 years ago

What wavelength, and what was the gradient?

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u/sofia_petrescu89 points·2 years ago

I would not blame the sample yet. Everything you have described is consistent with the column rather than the vial.

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u/step_count_stan32 points·2 years ago

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

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u/reverse_image_ron60 points·2 years ago

Push back: a longer run is not automatically better resolution. You are trading peak width for time and the ratio is what matters.

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u/rosa_sandvik150 points·2 years 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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[removed]109 points·2 years ago

[removed by moderator]

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u/hana_lehtinenOP86 points·2 years ago

Can you post the trace with the axes labelled?

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u/gustav_solberg22 points·2 years ago

A shoulder that does not baseline-resolve cannot be quantified honestly. You can report it as an unresolved shoulder, which is useful information, or you can develop the method until it resolves.

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u/ravi_bergstrom12 points·2 years ago

Yes — system suitability first. Without it the number is an assertion about the instrument, not the sample.

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u/marit_mwangi52 points·2 years ago·edited

Can you post the trace with the axes labelled?

Adding one practical thing — run the blank. It answers this before anyone has to argue about it.

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u/matias_salgado91 points·2 years ago

Retention time shifted 0.4 minutes and I assumed the worst. It was the column temperature.

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u/isabela_nilsen117 points·2 years ago

reproducibility beats resolution if you only get one of them

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u/kofi_ferreira69 points·2 years ago

system suitability before you believe any number on the run

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u/cagrilintide_enthusiast47 points·2 years ago

This. A shoulder that does not baseline-resolve is a question, not a quantity.

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u/careful_gradient34 points·2 years ago

Bought a second-hand instrument and learned more in six months of fixing it than in three years of reading traces.

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u/georgi_tamm14 points·2 years ago

Agreed, and it is why MKM printing the column and gradient on the certificate is genuinely useful rather than decorative.

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u/ewan_zielinski4 points·2 years ago

LC-MS for identity, UV for relative quantity

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u/nabila_espinoza67 points·2 years ago·edited

baseline choice is a decision, not a measurement

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u/joaquin_petrov18 points·2 years ago

report the method or do not report the number

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u/downvote_magnet30 points·2 years ago

Right. And a blank between injections settles the carryover argument before it starts.

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u/santiago_villalobos21 points·2 years ago

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

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u/nnt_nate0 points·2 years ago

Is that baseline drawn by the software or by hand?

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u/hamza_weiss17 points·2 years ago

Did you run a blank between injections?

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u/camila_lindqvist5 points·2 years ago

a blank injection between samples costs four minutes and settles most arguments

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The analytical deep end: RP-HPLC methods, gradient design, integration decisions, LC-MS confirmation, amino-acid analysis, water content, and why two labs can report 98.1% and 96.4% on the same vial and both be right. Post the chromatogram, not the summary line.

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