Limit of detection: difference between revisions
Diff·revision 3 → 4·13:36, 14 Sep 2024
Difference between revision 3 and revision 4 of Limit of detection. 6 lines changed; the page grew by 815 bytes.
| Revision 3 — 21:31, 27 Aug 2024 NewLabNell (talk) clarify the difference between related substances and total impurities 1,742 bytes ±0 | Revision 4 — 13:36, 14 Sep 2024 CRP_Cormac (talk) rm the claim that the method is stability-indicating without a forced-degradation study 2,557 bytes +815 | ||
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| 10 | The distinction is practical rather than pedantic. Between the two limits an analyte is detectable but not measurable, and a determination reported in that region carries an uncertainty comparable with the value itself.{{r|ich_q2}} | 10 | The distinction is practical rather than pedantic. Between the two limits an analyte is detectable but not measurable, and a determination reported in that region carries an uncertainty comparable with the value itself.{{r|ich_q2}} |
| 11 | 11 | ||
| + | 12 | For peptide impurity work the relevant question is usually not what the limit is in absolute terms but whether it is below the reporting threshold. An impurity present at 0.05% is irrelevant if the method cannot see below 0.5%, and a certificate reporting "no impurities detected" is a statement about the method as much as about the material.{{r|usp1503}} | |
| + | 13 | ||
| 12 | == How it is determined == | 14 | == How it is determined == |
| 13 | Three approaches are recognised. The signal-to-noise approach compares the analyte signal with baseline noise and takes a ratio of about 3:1 for detection and 10:1 for quantitation; it is simple and is the usual choice for chromatographic methods. The standard-deviation-of-the-blank approach uses replicate blank measurements. The calibration-curve approach uses the residual standard deviation of the regression and its slope.{{r|ich_q2}} | 15 | Three approaches are recognised. The signal-to-noise approach compares the analyte signal with baseline noise and takes a ratio of about 3:1 for detection and 10:1 for quantitation; it is simple and is the usual choice for chromatographic methods. The standard-deviation-of-the-blank approach uses replicate blank measurements. The calibration-curve approach uses the residual standard deviation of the regression and its slope.{{r|ich_q2}} |
| ⋮ | ⋮ | ||
| 15 | The three do not necessarily agree, and a reported limit should state which was used. Signal-to-noise figures in particular depend on how noise was measured — over what region of the baseline, and after what smoothing — and are not comparable between laboratories without that detail. | 17 | The three do not necessarily agree, and a reported limit should state which was used. Signal-to-noise figures in particular depend on how noise was measured — over what region of the baseline, and after what smoothing — and are not comparable between laboratories without that detail. |
| 16 | 18 | ||
| + | 19 | The limit is a property of the method as applied, not of the technique. The same instrument with a longer injection, a more concentrated preparation or a more sensitive detector setting has a different limit.{{r|usp621}} | |
| + | 20 | ||
| 17 | == References == | 21 | == References == |
| 18 | {{reflist}} | 22 | {{reflist}} |
| 19 | <ref name="ich_q2">International Council for Harmonisation, ''Q2(R2): Validation of Analytical Procedures'' (2023).</ref> | 23 | <ref name="ich_q2">International Council for Harmonisation, ''Q2(R2): Validation of Analytical Procedures'' (2023).</ref> |
| + | 24 | <ref name="usp1503">United States Pharmacopeia, General Chapter <1503>, ''Quality Attributes of Synthetic Peptide Drug Substances''.</ref> | |
| + | 25 | <ref name="usp621">United States Pharmacopeia, General Chapter <621>, ''Chromatography''.</ref> | |
| 20 | 26 | ||
| 21 | {{DEFAULTSORT:Limit of detection}} | 27 | {{DEFAULTSORT:Limit of detection}} |