The continued advancement of chromatographic techniques and mass-spectral instrumentation will undoubtedly open up new applications for mass spec-trometry in natural products discovery. The development of new chromato-graphic approaches, such as turbulent-flow chromatography [143], monolithic column supports [144], and ultraperformance liquid chromatography (UPLC) [145] promise to improve the speed and efficiency of natural product screening and purification. New mass spectrometers including ion-trap-FTMS systems promise to combine pulsed positive/negative ionization, sub-100 ppb mass accuracy [146] with MS, MS/MS, and MS" spectra to provide an extremely powerful set of tools for the structural elucidation of natural products. The recent development of mixed-mode sources combining ESI with APCI, APCI with atmospheric-pressure photoionzation (APPI), or ESI with APPI should expand the range of chemistries accessible to LC-MS [147-150]. The combination of ESI with APCI for small neutral chemistries, or APPI for enhanced ionization of aromatic neutral molecules [151], has potential application in both the dereplication and identification of natural products using LC-MS.

Mass spectrometry has been, and will continue to be, a critical tool for the discovery of new lead chemistries from nature. It continues to play a central role in several phases of the natural products discovery processes that include: source selection, screening, dereplication, and identification. Mass spectrom-etry will likely remain a key technology that should contribute to the success of natural product lead generation programs in both the pharmaceutical and agrochemical industries.

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