The optimal sample diluent is to dissolve your sample in your starting mobile phase which ensures the compounds reach the column in their desired state for interaction with the stationary phase. If working in an ion-paired system it is also good practice to add ion pair reagent into your diluent.
If you have to inject in a stronger solvent one solution is to inject a volume small enough that when it reaches the mobile phase it equilibrates almost instantaneously with the sample injection. This will serve to minimize the effect of the strong injection solvent.
In a preparative environment where samples are often insoluble unless strong organic solvents such as DMSO are used you can improve your peak shape by introducing an inline filter at the head of the column which acts as a pre-column mixing chamber and disrupts the effects of the strong solvent
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