Practical Applications of Monolithic Columns to Pharmaceutical Process Development

Abstract

High performance liquid chromatography (HPLC) is among the most widely used analytical techniques in the process development of drug substances. With the goal of reducing analysis time, there has been considerable focus on high‐speed HPLC separations. Recently, commercially available monolithic columns have proven to be one of the most promising developments in the area of fast chromatographic separations. In this work, pressure drop, column efficiency, and retention behavior of monolithic columns (Chromolith type) were evaluated and compared with those of conventional columns packed with porous stationary‐phase particles. It was demonstrated that high‐speed HPLC separations could be achieved with monolithic columns at acceptable pressure drops without significantly compromising column efficiency. The applications of monolithic columns in pharmaceutical process development, such as reaction monitoring, column fraction screening, and analysis of mother liquors and unstable analytes, are described with respect to the quality of separations, as well as, enhanced throughput and speed of analysis. It is concluded that the use of monolithic columns offers a significant advancement over currently available techniques in the high‐speed and high‐throughput analysis of pharmaceutical compounds. Some practical aspects in utilizing monolithic columns for fast separations are also discussed.