This paper describes an automated analytical system for the examination of protein primary structure in which (i) the target protein is first purified by immunoaffinity chromatography, (ii) subsequent chromatographic and chemical reaction steps in the sequencing process are directly coupled, (iii) buffer exchange between these unit operations is achieved while the protein is absorbed on a mixed bed of strong ion exchange sorbents, (iv) proteolysis occurs in an immobilized trypsin column having a 10-1000 fold-excess of enzyme, (v) the tryptic digest is directly transferred to a perfusion dilute capture column where it is concentrated and rapidly desalted, and (vi) peptides eluted from the dilute capture column and analytical microbore and capillary perfusion reversed-phase chromatography columns are analyzed by either single-stage mass spectrometry (MS) or tandem MS/MS. Protein structure variants were easily recognized, and in the case of hemoglobin (Hb) S, the site of variation from Hb A0 was verified.

There is a continuing need for increased throughput in the evaluation of new drug entities in terms of their pharmacokinetic parameters. One useful parameter that can be measured in vitro using liver microsomal preparations is metabolic stability. In this report, we describe an automated system that can be used for unattended quantitative analysis of liver microsomal samples for a series of compounds. This system is based on the Sciex API 150 (single quadrupole) liquid chromatography/mass spectrometry system and utilizes 96-well plate autosampler technology as well as a custom-designed AppleScript which executes the on-line data processing and report generation. It has the capability of analyzing at least 75 compounds per week or 300 compounds per month in an automated fashion.

There is a continuing need for increased throughput in the evaluation of new drug entities in terms of their pharmacokinetic parameters. One useful parameter that can be measured in vitro using liver microsomal preparations is metabolic stability. In this report, we describe an automated system that can be used for unattended quantitative analysis of liver microsomal samples for a series of compounds. This system is based on the Sciex API 150 (single quadrupole) liquid chromatography/mass spectrometry system and utilizes 96-well plate autosampler technology as well as a custom-designed AppleScript which executes the on-line data processing and report generation. It has the capability of analyzing at least 75 compounds per week or 300 compounds per month in an automated fashion.