Chromatography Forum

I'm planning to include Changing of Mobile Phase Composition as part of my Robustness test. The original composition of My MP is 43:57 Acetonitrile:Sodium Dodecyl Sulfate Solution. What changes in composition can I made as per ICH guidelines? Thanks.

This is obviously a case where you are validating your own test procedure, as USP test procedures (per USP and ICH) do not require additional robustness studies, as I understand things.

There don't seem to be guidelines for this, so whatever limits works for you and you document this, then you can be within your own proven limits.

35 and 50% ACN may be too wide to work, I'd try first, would be nice for you if such broad conditions did work. Realistically, 40 and 45% ACN may be better choices.

As CPG stated, there aren't any regulations around robustness. I typically include robustness as part of the method development process and document it accordingly in the method development report. A standard mobile phase composition adjustment for robustness is 2-5%. Say you choose 5%. If your original conditions are 43:57, you should perform two robustness studies: one at 38:62 and the other at 48:52.

This is obviously a case where you are validating your own test procedure, as USP test procedures (per USP and ICH) do not require additional robustness studies, as I understand things.

There don't seem to be guidelines for this, so whatever limits works for you and you document this, then you can be within your own proven limits.

35 and 50% ACN may be too wide to work, I'd try first, would be nice for you if such broad conditions did work. Realistically, 40 and 45% ACN may be better choices.

thanks for your comment

As CPG stated, there aren't any regulations around robustness. I typically include robustness as part of the method development process and document it accordingly in the method development report. A standard mobile phase composition adjustment for robustness is 2-5%. Say you choose 5%. If your original conditions are 43:57, you should perform two robustness studies: one at 38:62 and the other at 48:52.

thanks for your comment

Do you generally do chrom robustness for impurities gradient method with such wide changes in organic composition? Many impurities methods I developed have lots of peaks (include placebo). So changing the organic composition by +/-2% or changing the slope of the gradient slight causes co-elution of peaks. As a result, strick control of the mobile phase conditions and the use of ID solutions need to be in place.

That's the whole point to robustness testing: to establish how tightly the conditions have to be controlled.

gtma: While many methods don't tolerate even small changes in mobile phase, I don't think there's ever any harm in determining robustness experimentally either way. If it's demonstrated that method performance suffers under certain conditions, the method can be written with appropriate system suitability requirements, etc, from the outset. Alternately, robustness might be improved at the cost of a longer run time by changing method parameters, which might be the best option depending on the intended purpose of the method.

thx all, I appreciate your feedback. We should be very careful in selecting the critical parameters/design space for gradient methods for impurities. Often, the critical paratmeters operating range are tigher than for isocratic method. If the critical parameters fail a wide range, one will have to go back and reassess at a narrower range to fully understand the method conditions operating range. Chromatographic robustness is probably the most time consuming, thought provoking, and critical part of the validation, especially for impurities method where the impurities results (not peak area) and relative retention time are assessed for several runs.