Validation by spiking

The question of how much degradation is sufficient to meet the objectives of stress studies is widely discussed, especially with respect to conventional therapeutics. A degradation level of 10-15% is considered adequate for validation of a chromatographic purity assay. Chromatographic methods for product-related impurities (including degradants) should be validated by spiking experiments... 

Thus we see that although six basically different methods have been used for the determination of chromium in a common, presumably stable and fairly constant biological substrate, blood, we do not know its chromium content. We cannot assume that the lowest value is the most correct since there may have been losses we can be quite confident that the high values were subject to some contamination. Yet every method was validated by spiking with known amounts of chromium, and even with labeled 51cr in some cases, with "excellent results." In many cases, blanks were mentioned as accounted for. If we cannot decide on the concentration of an inorganic element at trace levels in blood, how can we do better with more complex and less stable organic molecules in this and other tissues ... 

Recoveries of dioxins through adsorbent columns must be checked and validated by spiking with known concentrations. Particular adsorbency... 

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