Liquid Chromatographic Assay of Drug substance

[nsreenivas]

Is that the Assay method developed for a Drug substance should be capable of covering all polar and non-polar impurities listed in its Related substances test? Please suggest.

regards,
n sreenivas

[Rob Burgess]

Not sure I read your question correctly, but if you are saying that an a stability indicating assay for drug substance should separate all polar and no-polar related impurities, then the answer is a definite yes!

[DR]

^ generally true, with some work but once in a while it takes a second method to get good data for a particularly "out there" related substance.

[ccyting]

I would like to add additional comments on the question. In general we have a low load (for active) and high load (for impurities and degradants) methods. For low sample load method, we will be able to do a high dilution of the sample to assay the active to avoid the overloading of the column. For high load method, it is for the relatively lower level of impurities and degradation products. The active method could be a relatiave short run time. Since at higher dilution, we will not observe the relatively lower level of impurities and degradation products. Of course, the lower level compounds will be retained in the column which will create late eluted peaks problem. Therefore, we need to do validation to define the total run time for a given run and the number of runs that we need to regenerate the column. We hesitate to do both active and other related peaks in a single run. Good luck.