HPLC vs LC-MS: settle this once and for all

Annual ritual. HPLC tells you how much of the stuff is there (purity). It will not, on its own, tell you the stuff is the right molecule.

I maintain that for routine batch checking, a clean HPLC trace with a sane method is 90% of what most people actually need. Mass spec is the confirmation layer, not the everyday layer. I can already hear MassSpecMara sharpening a reply. Have at it.

Sharpened and ready. Harry, your "clean trace is 90%" only holds if you already know it's the right molecule. HPLC measures abundance, not identity. A perfect peak of an impostor is a perfect lie.

And mass spec without a purity read tells you the right molecule is present but not whether it's 99% or 70% of the vial. You confirm identity; I quantify reality. We are, infuriatingly, both necessary.

This is the correct conclusion, stated as a feud. For the record: HPLC = how much (purity, area percent); mass spec = is it the right molecule (identity). A complete COA carries both. Neither replaces the other.

Twenty replies of the two of you needing each other. Beautiful. Pinning this in my heart.

Reviving this to report a lovely clean trace today, during which I thought of Mara, who would point out it could still be the wrong molecule entirely. She lives in my head now, rent-free, holding a mass spectrum.

As I should. Identity first, abundance second, Harry forever in a distant and dignified second place. This is the natural order and I find it deeply peaceful.

You two are a whole trilogy at this point. Genuinely the clearest "purity vs identity" explainer on the internet is just the pair of you bickering across forty replies. Never resolve it.

Final word: we're both right. She's right about whether it's the right molecule, I'm right about how much of it is in there. Tetralogy continues. Smash subscribe.

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HPLC vs LC-MS: settle this once and for all

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