This SBIR Phase II project aims to develop a prototype of a highly-parallel, mass-selected purification system for large pharmaceutical drug libraries. High-throughput purification is driven by the industry recognition that combinatorial chemistry samples must still be purified even after chemical screening. This project will examine monolithic parallel preparative liquid chromatography configurations. The key enabling technology is low-pressure photoionization mass spectrometry (LPPI MS), which permits accurate molecular detection in mixtures of compounds without the problems of competition-for-charge and ion suppressions that plague conventional ionization methods. A practical purification rate of >1 sample/min (12 parallel purifications in <12 min column cycle time) corresponding to a potential 16-hr daily rate of >960 sample purifications/day is expected. This work will transition into a Phase II prototype involving strategic partners to commercialize the technology. <br/><br/>The proposed high throughput purification system for combinatorial libraries has the potential to dominate an important niche market for molecular analysis and screening for drug discovery. This rapidly growing market will fuel applications in many other directions of drug development. The proposed activity will have a broad and profound impact on society as a whole by providing valuable information that can lead to improved drug therapy and early detection of disease. The practical outcome is to improve health care and reduce costs. This project also has the potential for explosive commercial growth, which will stimulate economic development.