Specificity, linearity, accuracy, precision, range, robustness — with real criteria — a second dataset posts 31–59

Answering the question post #29 raises rather than the one it answers.

Offering a way to settle Specificity rather than another opinion about it. Two measurements, taken the same way, a fortnight apart. If the difference is within the noise, the question was not answerable at this precision.

The arithmetic in post #29 is right; the assumption feeding it is the part to check.

Accuracy for a purity assay is usually demonstrated by spike recovery across a range. Without a reference standard, that is exactly the work that cannot be done, which is why reference material matters.

Filing this under things that are true until someone shows me otherwise.

Noted, and I have changed what I was going to do on the strength of it.

Specificity: the method can distinguish the intended compound from related impurities and degradation products. Tested by comparing results on pure compounds, mixtures of compounds, and degraded samples.

Post #34 describes the usual case. This is about the unusual one.

Linearity across the working range is a routine demonstration and it constrains how far a result can be extrapolated. A method linear from 80 to 120 per cent of nominal says nothing about a sample at ten per cent.

Two people can read the same figure differently here and both be reasonable.

Robustness testing deliberately varies the parameters most likely to drift — organic percentage, pH, temperature, flow — and shows the result does not. It is the part of validation that predicts whether a method will transfer.

One of those cases where knowing the mechanism does not help the decision.

Forced degradation under acid, base, oxidation, heat and light is how specificity is actually demonstrated. The chromatograms from that work are more informative than the release data.

Confirming post #37 from a second method, which matters more than confirming it from a second person.

Reframing Specificity slightly, because I think the disagreement is about the question rather than the answer. If the question is "does it happen", yes. If it is "how often", nobody here knows.

System suitability: injections run at the start of a batch to establish that the instrument and column are performing. Acceptance criteria typically include replicate precision (RSD ≤2%), peak tailing (0.8–1.5), theoretical plates (>2000), and resolution (>1.5).

Worth one more sentence than it usually gets.

Range: the concentration range over which the method has been validated. Going outside the validated range is going outside the method's demonstrated performance.

Small point, but it is the one that usually catches people.

Reading back through the Specificity threads from last year, the same three questions come up every time and only one of them has ever been answered properly. That seems like a documentation gap rather than a knowledge gap.

Limits of detection and quantitation: LOD is the lowest concentration that produces a signal above background. LOQ is the lowest concentration at which the method meets precision and accuracy acceptance criteria. Both are determined empirically.

If anyone has run this properly I would rather read that than my own guess.

This is the sort of exchange that makes the archive worth searching.

Worth separating two things that post #40 runs together.

Taking Specificity seriously for a moment rather than deflecting: the honest position is that the community has observations and no controlled comparison, and those two things support very different sentences.