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ForumsCOA & Analytical TestingBatch-to-batch purity variation — looking for input

Batch-to-batch purity variation — looking for input

Dr.EndoIndy Mon, May 26, 2025 at 6:39 AM 17 replies 1,487 viewsPage 1 of 4
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Dr.EndoIndy
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Indianapolis, IN
May 26, 2025 at 6:39 AM#1

Two reports on the same product from two laboratories, four percentage points apart, and no method stated on either.

The four things to check on any report, in order: does it name your batch, who commissioned it, what method was used, and does it report content as well as purity. A report failing any of those is weak evidence regardless of the percentage on it.

What I am after is whether a purity figure and a content figure can disagree without one of them being wrong.

I would rather have one careful answer than five confident ones.

44 14mia_MS2, LeilaHI, marcus_mpls and 41 others
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Dr.PainCLE
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May 26, 2025 at 8:47 AM#2

Taking the question as asked, rather than the general version of it. Inter-laboratory variation comes from real methodological differences, not sloppiness: which reference standard was used and how it was itself calibrated, the gradient and column, the detection wavelength, and where the integration baseline was drawn. A percentage point or two between competent labs is expected. What is not expected is a large gap, and the usual explanation there is that one report is not of the batch in your hand.

Last edited: May 26, 2025 at 11:47 AM
43 13tane_welly, Dr.PathRoch, mona_PHX and 40 others
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LindaRN_retired
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May 26, 2025 at 10:55 AM#3
Dr.PainCLE said:
Inter-laboratory variation comes from real methodological differences, not sloppiness: which reference standard was used and how it was itself…

Dr.PainCLE has the substance of this right. The condition it depends on is worth stating. One addition: an unstated method makes a report close to uninterpretable. "99% pure" without the technique, the standard and the conditions is a claim, not a measurement.

42 12amsterdam_pete, LondonLisa, mike_nyc and 39 others
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paige_pharma
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May 26, 2025 at 1:03 PM#4
Dr.EndoIndy said:
Two reports on the same product from two laboratories, four percentage points apart, and no method stated on either.

Can confirm the pattern Dr.EndoIndy describes. They are not contradictory, they measure different things, and this is the single most common misreading of a certificate. Purity is a relative area measurement: the main peak as a percentage of total peak area in the chromatogram. Content is an absolute mass measurement against a reference standard. A vial can be 99% pure and contain 6.1mg — pure material, overfilled — or 99% pure and contain 3mg, which is pure material and a short fill. Purity tells you what fraction of what is there is the right molecule; content tells you how much of it there is. You need both, and a certificate with only purity is telling you half the story.

41 11lisa_labSD, adam_van, Dr.SurgeonPGH and 38 others
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Dr.GastroMayo
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May 27, 2025 at 1:46 AM#5

Adding the clinical framing, because it changes how the question reads.

COA red flags for certificates of analysis — here's what to look for when reviewing a Certificate of Analysis:

  • No HPLC data: If there's no chromatography graph, it's not a real COA
  • Exact 100% purity: Suspicious — real testing always shows slight variation
  • No batch number: Can't trace back to specific production
  • No endotoxin testing: For injectables, this is essential
  • Template looks like it was made in Word: Professional labs have standardized formats

I have seen fake COAs that are literally photoshopped. Always verify independently if possible.

40 10InsuranceTom, WendyG_ATL, SaraMom3 and 37 others
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