Medicinal chemistry has prompted a rush in the development of analytical methods which are well suited to both high throughput and positive identification, including mass spectrometry (MS). For the past two or three years, considerable efforts have been expended to tailor existing MS and LC-MS products to this burgeoning group of users in """"""""discovery"""""""". While great utility is being derived from current instruments and methods, much can be done in LC-MS to address both theoretical sample throughput and analytical performance. To simultaneously address both sample throughput and analytical performance, a microscale version of a research grade atmospheric pressure chemical ionization (APCI) interface will be designed, built and tested in conjunction with a microbore liquid chromatography system. The composite Lc-APCI-MS system will have throughput and performance features which are heretofore impossible to achieve using conventional (but proven) 4.6 mm column technology, requiring a small fraction of the analyte and solvent currently required but delivering hundreds of times better limits of detection. Moreover, the composite system will allow very fast liquid phase separations (less than 60 seconds) while retaining most or all of the chromatographic resolution possible in HPLC. The methods generated on this hardware configuration will be rugged and highly reproducible, using all commercially available (microscale) HPLC equipment, thereby hastening required methods validation procedures.
The proposed microflow APCI interface for mass spectrometry is intended to improve the limits of detection for trace non-polar species in complex mixtures (such as those generated in split syntheses) while at the same time making on-line coupling to microbore chromatographic methods easier, more reproducible and robust enough to warrant attention from users in high throughput, automated LC-MS settings.
