Establishment of a High-Resolution Liquid Chromatography–Mass Spectrometry Spectral Library for Screening Toxic Natural Products

Abstract

Many natural products have biological effects on humans and animals. Poisoning caused by natural products is common in clinical toxicology cases. Liquid chromatography-high-resolution-mass spectrometry (LC-HRMS) has recently emerged as a powerful analytical tool for large-scale target screening, and the application of LC-HRMS can be expanded to evaluate potential natural product poisoning in clinical cases. We report the construction of an LC-HRMS spectral library of 95 natural products commonly implicated in poisoning, and an LC-HRMS assay was validated for definitive detection of natural products in urine and serum samples. For each compound, the limit of detection (LOD) was determined in the analytical range of 1.0 – 1000 ng/mL for urine samples and 0.50 – 500 ng/mL for serum samples. The mean (SD) of matrix effects for urine samples and that for serum samples were both -21% (22%), and the mean (SD) of recovery for serum samples was 89% (26%). The LC-HRMS assay was successfully applied to identify natural products in clinical cases. The spectral library parameters of each compound are provided in the supplementary material to aid other laboratories in identification of unknown natural toxins and development of similar methods on different mass spectrometry platforms.

The promising guide to LC–MS analysis and cholinesterase activity of Luffa cylindrica (L.) fruit using in vitro and in-silico analyses

“…Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) has become a robust analytical method for massive target screening. Its use can be expanded to assess the possibility of natural product poisoning in clinical situations [65]. An ultraperformance liquid chromatography-quadrupoletime-of-flight-mass spectrometry has been employed in several studies to characterize the potential components [66].…”

Annotation of DOM metabolomes with an ultrahigh resolution mass spectrometry molecular formula library

“…To identify molecules, their mass and retention time can be matched to those of authentic standards. When tandem MS/MS capable instruments are used, features are more commonly identified by comparing their fragmentation spectra to databases of MS/MS spectra from authentic standards (e.g., Milman, 2005; Schymanski et al, 2014; Luo et al, 2016, 2023; Folberth et al, 2020). This approach provides confident molecular formula identification of metabolites as well as structural information, with the expectation that molecular isomers with the greatest structural similarity will yield the highest scoring MS/MS spectral match (Schymanski et al, 2014).…”

“…To identify molecules, their mass and retention time can be matched to those of authentic standards. When tandem MS/MS capable instruments are used, features are more commonly identified by comparing their fragmentation spectra to databases of MS/MS spectra from authentic standards (e.g., Milman, 2005;Schymanski et al, 2014;Luo et al, 2016Luo et al, , 2023Folberth et al, 2020). This Click here to enter text.…”

Comparison of liquid chromatography-high-resolution tandem mass spectrometry (MS2) and multi-stage mass spectrometry (MS3) for screening toxic natural products

“…This methodology shows excellent performance in the identification of compounds in complex biological matrices. [1] , [2] , [3] For some instrument platforms, additional generations of product ions can be produced via fragmentation, often referred to as multi-stage mass spectrometry (MS n ). [4] MS 3 product ions can be generated from an MS 2 product ion.…”

“…Previously we described an LC-HR-MS (MS 2 ) method for the identification of toxic natural products. [3] , [14] It is currently unknown whether utilizing LC-HR-MS 3 provides enhanced performance for identifying small molecules in clinical toxicology cases in comparison to MS 2 . To evaluate the potential of LC-HR-MS 3 in detecting toxic natural products, a spectral library of 85 natural products containing both MS 2 and MS 3 mass spectra was constructed using a quadrupole-linear-ion-trap-Orbitrap tandem mass spectrometer.…”