HPLC validation - accuracy determination issue

[Robotjock]

A colleague needs to determine accuracy (impurity level) of a method but the material has a high impurity content which will confound the true recovery. Said colleague states that because the impurities and parent compound are well separated by the chromatography, the parent will have no impact on the impurity analysis. Thus, it is not necessary to have the parent material present in the impurity validation test solutions, i.e., neat solutions not spiked solutions.

Pretty sure this is not ICH compliance, but would like input from others..

How would one solve a high impurity content issue?

regards,

[KM-USA]

Standard addition quantitation.

[gtma]

Std addition works okay for low impurities levels in the spike std. However, if the impurities are above the LOQ in the spiked std, then you may want to consider spiking the placebo with a lower std conc (where the impurities is significantly reduced) plus the neat impurities. Spiked neat impurities only in placebo should be your last resort.