IMPACT ON DRUG IMPURITY PROFILING WITH SUB 3μM HPLC COLUMN PACKINGS

摘要

Recently there has been great interest in the use of smaller column packing materials for HPLC separations. The -smaller packing materials promise several benefits such as increased efficiency, increased resolution, and decreased run times. Over the last four years, several vendors have marketed sub 2 μm packing materials, and very recently some vendors have offered materials in the 2.2 - 2.5 μm range. In general, commercially available materials less than 2 μm in diameter have surface areas in the range of 170 -200 m~2/g. Last year, a series of 2.5 pm particles were introduced having surface area in the 400 m~2/g range. Theoretically these higher surface area materials should provide a greater number of available stationary phase ligands to interact with the analytes in the column. Overall this increased surface area should increase the column loadability. One key analytical area where column loadability is a major concern is drug impurity profiling assays, where a large amount of the main component must be loaded onto the column in order to increase the detectability of trace contaminants. Typically it is necessary to quantitate the impurities at the 0.05 -0.1% level compared to the main peak area. In this paper, we examine the loadability of commercially available sub 3 μm stationary phases, and investigate the role that media surface area has on loadability and how this impacts impurity-profiling assays.