LC/MS: A Molecular Fingerprint for Botanical Drugs

Botanical extracts are multicomponent drugs that require detailed chemical fingerprint analysis as the first critical step in assessing overall material quality. High-resolution capillary liquid chromatography (LC), coupled with ultra high resolution mass spectrometry (MS), offers a sensitive method to detect and identify a large number of diverse phytochemicals and provides a reliable and accurate molecular fingerprint that can be quantitatively compared with other samples. This state of the art analytical method, integrated with comprehens ve chemo nformat cs, prov des a powerfu methodology for the analysis of botan ca extracts that can be developed into a systematic and standardized platform for botanical quality control. In this proposal we focus on two specific aims utilizing our development drug candidate PHY906: !Specific Aim 1: Develop a standardized analytical protocol for phytochemical identification by (a) combining LC/MS and evaporative light scattering detection (ELSD) for botanical extract characterization (b) comparing ionization methods for phytochemical MS detection (c) automating the process of LC/MS data collection and chemoinformatic database analysis to rapidly and accurately identify phytochemical compounds in traditional Chinese medicin e (TCM) formulations. Specific Aim 2: Demonstrate the utility of LC/MS for botanical chemical fingerprinting by (a) developing software for selecting optimized sub-sets of LC/MS peaks for similarity comparisons (b) characterizing different extraction methods and defining a quantitative molecular fingerprint signature (c) utilizing a novel similarity index metric for comparing botanical patterns. Our long term goal is the standardization of a LC/MS platform for the quality control of PHY906 and other botanical drugs and the development of an FDA approvable process for phytochemical identification, unique molecular fingerprint pattern determination and quantitative botanical similarity assessment.