Application of High Throughput LC/MS on Drug Metabolism and Pharmacokinetics in Drug Discovery

Abstract

Pharmacokenetic (PK) properties have been recognized as one of the most important attrition factors in the drug development. Recently, there has been a substantial increase in the variety and number of newly synthesized compounds in the drug discovery stage. Therefore, an improved capacity to evaluate such huge numbers of compounds is one of the most important needs for high-throughput screening. One key to successful analysis technology for PK studies is the LC/MS. However, there is a problem to establishing high-throughput LC/MS. It is important that a suitable LC system is selected from various instruments to analyze with accuracy. For example, short columns, parallel LC systems, unique types of columns, and high flow assays have been examined to find the most rapid and efficient analysis systems. Impurities from reaction mixture or medium should be separated from analytes to get stable detection, as those can alter the ion effect of analytes. In addition to developing these methods, keeping the LC/MS system a good working order is also important, as high-throughput LC/MS is used for continuous screening. High-throughput LC/MS will be indispensable technology to PK studies in drug discovery, but much work has to be done in order to determine which optimal condition will be developed.