Start from the question: how many vials from this lot do I need to test to claim that the lot meets specification, and the answer depends on both the lot size and the acceptable risk.
Under AQL sampling plans, testing two vials from a fifty-vial lot gives you an operating characteristic curve that tells you what risks you are accepting.
Mass shifts and what they usually mean
| 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 |
Mechanically, the statistical foundation here is well-established, which is why sampling plans from decades ago are still valid.
Published data on lot homogeneity from manufacturers who sample multiple vials consistently find variation below the published specifications, suggesting the sampling plans work.
I would treat a "complies with" statement without sampling details as a claim rather than as evidence.
If testing multiple vials, state how many you tested and why you chose those vials.