Emerging Analytical Separation Techniques with High Throughput Potential for Pharmaceutical Analysis, Part I: Stationary Phase and Instrumental Developments in LC

Sigrid      Pieters; Birke      Dejaegher; Yvan      Vander Heyden; Bieke      Dejaegher

Abstract

In recent years, a trend of change has been observed within pharmaceutical industry. As modern drug discovery has reached a remarkable level of complexity and drugs need to be discovered, developed and produced against strict timelines and within cost- and regulatory constraints, industry seeks “lean” solutions to increase productivity. Among them, increasing the sample throughput of the ever-growing number of necessary (routine) analyses has become a popular target to cut precious time. For the last thirty years, High-Performance Liquid Chromatography (HPLC) has been the leading technology when it comes to various analyses in pharmaceutical industry; however, its necessity of serial analyses taking typically 10-45 min has been a sample throughput-limiting barrier. Lately, the fundamentals of HPLC have been exploited to raise new technologies that can speed up analyses to ground breaking limits, without compromising separation efficiency. This paper reviews some promising technologies, i.e. totally porous sub-2μm particles accompanied by pressures up to 1000 bar (Ultra-Performance Liquid Chromatography or UPLC), fused-core particle technology, monolithic supports and High Temperature Liquid Chromatography (HTLC), having the potential to take LC to the next level in pharmaceutical industry. As each analytical method has its own demands, the advances of the above technologies are discussed for different applications in pharmaceutical analysis where high throughput analysis can be meaningful, i.e. in a drug discovery and development setting, and in quality operations. Both chemical and biological pharmaceuticals are considered. We discuss the perspectives of these technologies and their realizations up to now in high throughput pharmaceutical analysis.

Keywords: High throughput, pharmaceutical analysis, HPLC, UPLC, fused-core particles, monolithic columns, HTLC, kinetic plots