Would you accept 98.2% on orforglipron from MKM without a content assay?

Details up front: 98.2% · orforglipron · MKM.

I would rather over-plan the first cycle and simplify later.

I am prepared to do the work if someone can tell me which work matters.

What is the minimum version of this that is still defensible?

Start from what the detector sees, because that tells you what the number means.

Mobile phase additive choice affects ionisation and peak shape — TFA gives sharp peaks but suppresses mass spectrometry signal, formic acid gives worse peaks but preserves signal.

Column pore size affects mass transfer — a 100 Angstrom packing on a 5 kDa peptide restricts diffusion, broadening the peak and potentially hiding small impurities in the shoulders.

The caveat is that purity without identity is only half an answer — a high purity does not mean the peak is actually what you think it is.

If you are ranking vendors, specify a method and have all samples tested at the same place.

Gradient slope is the most powerful parameter and almost nobody mentions it, which is why two reports on the same material disagree by a point.

Retention time is sequence-specific and method-specific, so comparing your result to a supplier value using a different method is meaningless without method documentation.

Mass on column affects detector linearity and peak overlap — overloading broadens peaks and hides neighbours, while underloading improves resolution but loses sensitivity.

Worth noting that method standardisation is poor in the research-grade space compared to pharmaceutical work, so identical-looking methods can produce different results.

Compare purity within a single laboratory on the same method, never across laboratories.

Identity and purity are orthogonal, and a high purity says almost nothing about whether the peak is actually what you think it is.

Sample solvent strength affects peak shape — if you inject in strong solvent on a gradient starting in weak solvent, the solvent peak can distort your main peak or create a false shoulder.

In practice, tailing factor measures peak shape, and a badly tailing peak spreads into the region where small impurities live, forcing tangent-skim integration that assigns tail area to the main peak.

The limitation is that single-digit micro-impurities become invisible at typical reporting thresholds, so "no impurities detected" means "none above one in two thousand."

The practical summary: ask for the chromatogram and the method, and ignore the headline number until you have both.

On the detail: the short answer is that two competent laboratories on identical material will disagree, and the disagreement is almost always explainable by method differences.

Integration of the shoulder — whether you use perpendicular drop or tangent skim — determines what area gets assigned to the main peak versus the impurity table.

If you are ranking vendors, specify a method and have all samples tested at the same place.

edited 10 May 2026 by tobias_maartens — added a caveat about sampling

Concretely, understanding purity requires separating the chemistry from the method from the reporting convention, and the three are not independent.

Temperature affects the dynamics of molecular conformation, and if a peptide has proline residues that interconvert on the chromatographic timescale, the peak will split or shoulder at low temperature and collapse at high temperature.

Inter-laboratory studies on identical peptide material routinely find half-a-per-cent to a full-per-cent spreads in reported purity on the same sample.

Compare purity within a single laboratory on the same method, never across laboratories.