Universal quantification of structurally diverse natural products using an evaporative light scattering detector

Abstract

A lack of good methods for absolute quantification of natural products has limited the accuracy of high-throughput screening. Many currently used methods for quantification are either too slow or not amenable to the structural diversity of natural products. Recent developments in low-temperature evaporative light scattering detectors (ELSD-LT) have overcome several historical limitations of ELSDs, including analyte decomposition and low sensitivity. Primarily, ELSDs have been used for relative quantification and detection of compounds that lack a UV chromophore. In this study, we employ an ELSD-LT for absolute quantification of natural products. Calibration curves were constructed using a weighted least-squares analysis for a diverse set of natural products and other compounds. An average calibration curve was evaluated for the "universal" quantification of natural products. Optimization of ELSD-LT hardware and parameters improved sensitivity and throughput and established the utility of ELSD-LT for quantification of large natural product libraries.

Figure 1

Effects of solvent composition and evaporation temperature on ELSD response.

Figure 2

Calibration curve of cycloheximide.

Figure 3

Comparison of standard calibration curves and construction of average “universal” calibration curve.