Degradation product identification, degradation pathway investigation, drug-formulation ingredient interaction, and extractables studies for NEC evaluation and marketed topical OTC product assessment are discussed.For marketed products, in addition to the value in safety and quality evaluation, the degradation mechanism information could also serve as a guideline for optimization of formulation, packaging, manufacturing, and storage condition.The power of a strategic combination of HPLC-MS with other novel anal. technologies such as HPLC-UV, HPLC-NMR, GC-MS, off-line NMR, and traditional semipreparative HPLC, chem. derivatization, and classic organic synthesis for structural identification was demonstrated.Oxidatively induced coupling of miconazole nitrate with BHT in a topical ointment, extractables or leachables from packaging including rubber closures of a prefilled semisolid drug applicator into drug products, novel degradation products and pathways of vitamin D and its analogs, thermal degradation of ecalcidene, and reductive degradation of a 1,2,4-thiadiazolium derivative, 2,3-bis(2-methoxyphenyl)-5-phenylamino-[1,2,4]thiadiazolium bromide were discussed.