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Natural products are the most consistently successful source of drug leads. The rapid identification of known compounds from natural product extracts, or 'dereplication', is an important step in an efficiently run drug discovery program. Modern spectroscopic methods have largely revolutionized compound identification and tremendously accelerated the pace at which isolated compounds can be identified. Dereplication strategies use analytical techniques and database searching to determine the identity of an active compound at the earliest possible stage in the discovery process. This prevents wasted effort on samples with no potential for development and allows resources to be focused on the most promising lead. In the past few years, advances in technology have allowed the development of tandem analytical techniques, such as HPLC-PDA, LC-MS, LC-MS-MS, LC-NMR, and LC-NMR-MS. This review describes the principles and performance of a number of hyphenated techniques involving LC-MS that can be used for dereplication of natural products for rapid lead identification.

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