New active, how to develop analytical methods?

[seamoro]

Hello, im just wondering if i receive a new API and am told to develop test methods for quantitation of the active and the related substances of that compound ...how would i go about this? i think i would do it like this...am i correct?
1. determine potential polarity by looking a its structure maybe run a quick TLC
2. on the basis of this information and with some solubility studys run it on LC-MS....identify active peak which will be largest peak and say there is maybe 3% impurties....so method development here...achieve adequate seperation.
3. with the identifaction of impurties and assignment of structure would i then move the method to HPLC?
could i do hplc prep work,TLC prep work or fractionation with column chromatography to collect isolated impurties and then develop HPLC assay method and related substances method? which could be introduced to QC.If you guys can give me some advice i would greatly appreciate it!

[Rob Burgess]

The 1st to do would be to ask questions - i.e. what is the structure of the API, mass, UV, functional groups, acid/base character, lipophilicity, solubility, synthetic route etc. etc. You wouldnt't just be given an API without any info whatsoever

Also depends on what stage of clinical development you are at whether you would need to identify the impurities/ Plus you would only need to identfy possibly those that are greater than your ICH threshold limits.

You would also need to look for impurities that are potentially genotoxic and those that have not been "safety" qualified in animal tox studies.