Numbers first: 95.2% · orforglipron · SSA.
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?
The honest answer is that the achievable range of plausible purity figures for a given vial is wider than most people expect.
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.
| Δ mass (Da) | Most likely cause | Distinguishing feature |
|---|---|---|
| +1 | Deamidation (Asn or Gln) | New peak, slightly earlier retention |
| −17 | Loss of ammonia | Often with deamidation |
| −18 | Dehydration / succinimide | pH-dependent, reversible |
| +16 | Oxidation (Met, Trp) | Earlier retention, light-related |
| −128 | Missing Gln or Lys | Deletion sequence from synthesis |
| 0 | Isomer: racemisation or scrambling | Same mass, shifted retention |
The relevant detail is that 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.
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.
If you are ranking vendors, specify a method and have all samples tested at the same place.
Aggregated, published test results and vendor ratings built from submitted batches. Methodology stated, dataset browsable, no listing fees.
Browse resultsThe method matters more than the vial, which is why specifying a method buys you far more than changing suppliers does.
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.
The Arrhenius relationship for peptide degradation is the basis of accelerated stability testing and also governs how quickly methods drift with temperature.
Compare purity within a single laboratory on the same method, never across laboratories.
edited 6 Nov 2024 by orla_ferriter — updated for the 2026 guidance change
Concretely, purity is a method-dependent figure, and that is not a limitation of the measurement, it is a property of what the measurement actually answers.
Gradient slope controls resolution, and gentler slopes resolve co-eluting impurities into separate peaks — so the better method reports the worse purity number.
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.
The ICH Q3A impurity thresholds and the relevant pharmacopoeial chapters all specify method validation requirements that almost no research-grade certificate claims to meet.
The practical summary: ask for the chromatogram and the method, and ignore the headline number until you have both.
The relevant detail is that read the chromatogram before you read the number, because the number without the trace is not a measurement, it is a claim.
The fraction of your main peak that is actually your target versus isomers, fragments or related sequences is invisible without complementary identity testing.
Proline conformer interconversion kinetics are well-characterised and the half-life is of the same order as the chromatographic peak width at room temperature.
If you are ranking vendors, specify a method and have all samples tested at the same place.
Put another way, reporting threshold is convention and not chemistry, which is why two certificates with different thresholds disagree by a tenth of a point or more.
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.
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.
edited 7 Sept 2024 by assay_blank — clarified the distinction between purity and content
Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.