Particulate matter testing — 6 month update

Short answer first, then the reasoning. 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.

kate.chem said:

Inter-laboratory variation comes from real methodological differences, not sloppiness: which reference standard was used and how it was itself…

Agreed, and mass spec answers a question purity does not: identity. High purity tells you one thing dominates the chromatogram, not that it is the molecule you ordered. A mass within about a dalton of expected is the identity check.

steph_laguna said:

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

This matches mine closely enough to be worth saying so. 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.

If somebody has the primary source to hand I would rather cite it than paraphrase it.

From the other side of the consultation, briefly.

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.