[mir]

Why do we choose Internal standards with retention time close to the analyte?

Every book I read says the same how important it is. But none of them explain axactly why.

Is it possible to use two internal standards with ret. times very different to the analyte, instead of one very close?

[Dude]

I don't think that you will find a valid reason for that comment today.  The statement probably is probably a historical carryover concept to eliminate condition variables (ie volatility at a GC inlet, band broadening in the column).  With the advent of temperature programming in GC and gradients in LC, there is probably not a valid reason for that recommendation today.  If response factors are accurate and there are no systematic problems, I believe that an internal standard one minute offset from your sample would provide no benefit to an internal standard five minutes offset from your sample.

[gkdmaths]

...I believe that an internal standard one minute offset from your sample would provide no benefit to an internal standard five minutes offset from your sample.

except for those four valuable minutes. 

/gkd