Being an amateur at method development, I'm struggling with choosing good internal standards for my reversed phase LC separation of a pesticide. Would like to hear suggestions of which ISTDs other of you are using. I know it depends on elution time but I'd like to hear if there are others than phthalates. BTW,is it more important to get an ISTD close to the elution time OR one chemically more similar to the peak of interest?

The first question to ask is why do you need an internal standard? Does your autosampler not work properly such that an internal standard is needed to measure the volume injected? In this case anyting will work, but it might be better to fix the autosampler. Is recovery of some extraction poor? Well, in this case the recovery properties of the internal standard must match the analyte, so it would need to be chemically similar. Is the detector response drifting? Then the drifting response of the internal standard better match the analyte. So, for example, in mass spec one might use a deuterated internal standard. In summary the internal standard is chosen to compensate for a known/demonstrated problem. Once your have identified the problem, a rational decison can be made about selection.

Keep in mind that there is a price to pay for using an internal standard. First, there is a 2X chance for interferance and second, the precision is going to be inherently worse becasue two peaks are measured to get an answer instead of one.

If you can't demonstrate that an internal standard improves precision, then don't use one. You will find that with a typical separation on typical equipment, and UV or RI detection, that an internal standard will rarely be beneficial.