Related Substances Method Validation - Limit of quantitation

[Mouleyre]

When validating a new drug product Related Substances Method - I have seen methods where LOQ solutions have been prepared and simply injected as is but also have seen LOQ solutions prepared and injected in Mobile Phase and Placebo.

Can it be explained the rationale behind spiking into Mobile Phase or Placebo Please?

[vmu]

rationale behind spiking into Mobile Phase

The rationale is the same as for any other solution injected to the column. The use of the mobile phase as the solvent prevents distortion of the peak shape and prevents appearance of undesirable "system" peaks.

spiking into ... Placebo

This can be reasonable when there is a placebo peak close to the peak of interest on the chromatogram. For instance, this allows one to verify that the tail of a large placebo peak does not reduce significantly or hide the small peak of interest.

The choice of the solvent also depends on the stability of the substances in the solution.

Note also that some method developers can make irrationale decisions and introduce unnecessary complications into their methods.