= Surrogate-matrix response equivalence
<Surrogate-matrix response equivalence> means that a specified <surrogate sample matrix> supports an adequately comparable analytical response to the authentic <sample matrix> over the method's intended range. Equivalence is tied to an <analyte>, preparation, detector and decision criterion. It does not require the materials to have identical chemical composition.
ICH M 10 calls for assessment of differences in <analytical matrix effects> and <extraction recovery> between surrogate and authentic materials, and evaluation of response parallelism across the range.<Bioanalytical Method Validation and Study Sample Analysis M10 by ICH>[§§7.1.2–7.1.3, surrogate/authentic comparisons and parallelism.]{ref} A useful experimental design processes authentic unspiked samples, authentic samples with known <analyte> increments and spiked surrogate material through the same procedure. The endogenous contribution in authentic material must be accounted for.
An original linear <measurement model> makes a one-point comparison's limitation visible. Let the surrogate response be $y_s=2c$, and the authentic response be $y_a=5+c$, where $c$ is the <analyte> <concentration> in stipulated units. Both give response 10 at $c=5$. At $c=15$, however, authentic material gives 20, and the surrogate calibration reports $c=10$. Agreement at the crossing point concealed both a slope difference and an offset.
Matched increments remove a constant endogenous offset: $\Delta y_a=s_a\Delta c$ and $\Delta y_s=s_s\Delta c$ in a linear range. Their ratio estimates $s_a/s_s$, provided additions do not themselves change the <sample matrix> or preparation. Similar slopes alone still do not establish identical blank interference, stability or behavior outside that range.
Set a comparison tolerance appropriate to the analytical use and examine uncertainty as well as nominal agreement. A wide uncertainty interval containing equal response is not strong evidence of equivalence. Likewise, matching a ratio normalized by an <internal standard> may be useful for that method while concealing unequal absolute <extraction recovery>; state which response has been compared.
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