US-20260128134-A1 - Creation of Realistic MS/MS Spectra for Putative Designer Drugs

US20260128134A1US 20260128134 A1US20260128134 A1US 20260128134A1US-20260128134-A1

Abstract

Systems and methods are provided for predicting the mass spectrum of an unknown compound. An experimental mass spectrum of a known compound is obtained. One or more mass peaks of the experimental mass spectrum corresponding to a substructure of the known compound are annotated with at least one modification an unknown compound is predicted to include. An in-silico mass spectrum is created for the unknown compound from the experimental mass spectrum and the annotated one or more mass peaks. The unknown compound is then identified from a sample by mass analyzing the sample, producing an unknown experimental mass spectrum, and comparing the unknown experimental mass spectrum to the in-silico mass spectrum.

Inventors

Lyle Lorrence Burton
David Michael Cox

Assignees

DH TECHNOLOGIES DEVELOPMENT PTE. LTD.

Dates

Publication Date: 20260507
Application Date: 20231006

Claims (16)

1 . A method for predicting the mass spectrum of an unknown compound, comprising: (a) obtaining an experimental mass spectrum of a known compound; (b) annotating one or more mass peaks of the experimental mass spectrum corresponding to a substructure of the known compound with at least one modification an unknown compound is predicted to include; and (c) creating an in-silico mass spectrum for the unknown compound from the experimental mass spectrum and the annotated one or more mass peaks.
2 . The method of any combination of claim 1 , further comprising adding the in-silico mass spectrum to a mass spectrum library.
3 . The method of any combination of claim 1 , wherein the in-silico mass spectrum is created by shifting a mass-to-charge ratio (m/z) of the one or more annotated mass peaks of the experimental mass spectrum according to the at least one modification.
4 . The method of claim 1 , wherein the one or more annotated mass peaks of the experimental mass spectrum are shifted to a higher m/z value in the in-silico mass spectrum according to the at least one modification.
5 . The method of claim 4 , wherein intensities of the shifted one or more annotated mass peaks of the in-silico mass spectrum are not changed from intensities of corresponding mass peaks of the experimental mass spectrum.
6 . The method of claim 1 , wherein the experimental mass spectrum, the in-silico mass spectrum, and the unknown experimental mass spectrum are product ion spectra.
7 . The method of claim 1 , wherein the known compound comprises a known drug of abuse and the unknown compound comprises a variant of the known drug of abuse.
8 . A computer program product, comprising a non-transitory tangible computer-readable storage medium whose contents cause a processor to perform a method for predicting the mass spectrum of an unknown compound, comprising: providing a system, wherein the system comprises one or more distinct software modules, and wherein the distinct software modules comprise an input module and an analysis module; obtaining an experimental mass spectrum of a known compound using the input module; annotating one or more mass peaks of the experimental mass spectrum corresponding to a substructure of the known compound with at least one modification an unknown compound is predicted to include using the analysis module; and creating an in-silico mass spectrum for the unknown compound from the experimental mass spectrum and the annotated one or more mass peaks using the analysis module.
9 . The computer program product of claim 8 , further comprising adding the in-silico mass spectrum to a mass spectrum library.
10 . The computer program product of claim 8 , wherein the in-silico mass spectrum is created by shifting a mass-to-charge ratio (m/z) of the one or more annotated mass peaks of the experimental mass spectrum according to the at least one modification.
11 . The computer program product of claim 8 , wherein the one or more annotated mass peaks of the experimental mass spectrum are shifted to a higher m/z value in the in-silico mass spectrum according to the at least one modification.
12 . The computer program product of claim 11 , wherein intensities of the shifted one or more annotated mass peaks of the in-silico mass spectrum are not changed from intensities of corresponding mass peaks of the experimental mass spectrum.
13 . The computer program product of claim 8 , wherein the experimental mass spectrum, the in-silico mass spectrum, and the unknown experimental mass spectrum are product ion spectra.
14 . The computer program product of claim 8 , wherein the known compound comprises a known drug of abuse and the unknown compound comprises a variant of the known drug of abuse.
15 . A system for identifying an unknown compound, comprising: a processor that obtains an experimental mass spectrum of a known compound, annotates one or more mass peaks of the experimental mass spectrum corresponding to a substructure of the known compound with at least one modification an unknown compound is predicted to include, creates an in-silico mass spectrum for the unknown compound from the experimental mass spectrum and the annotated one or more mass peaks, obtains an unknown experimental mass spectrum of the unknown compound, and determines that the unknown compound is a modification of the known compound if the unknown experimental mass spectrum matches the in-silico mass spectrum.
16 . The system of claim 15 further comprising a mass spectrometer and wherein the processor instructs the mass spectrometer to analyze the unknown compound to produce the unknown experimental mass spectrum.

Description

RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application Ser. No. 63/378,594, filed on Oct. 6, 2022, the content of which is incorporated by reference herein in its entirety. INTRODUCTION The teachings herein relate to predicting the mass spectrum of an unknown compound. More particularly the teachings herein relate to systems and methods for annotating mass peaks of a mass spectrum of a known compound with at least one modification an unknown compound is predicted to include and creating an in-silico mass spectrum for the unknown compound from the experimental mass spectrum and the annotation. The systems and methods herein can be performed in conjunction with a processor, controller, or computer system, such as the computer system of FIG. 1. Compound Identification Problem Compound identification of unknown compounds is a very difficult problem. It is especially difficult when the compound is novel and has not been previously or widely described in the literature. A scenario encountered, for example, in the forensics laboratory is the need to identify a compound believed to be potentially responsible for a fatality. A mass spectrometry/mass spectrometry (MS/MS) or product ion mass spectrum may be obtained for a sample believed to contain the compound. A suspected mass peak for the compound and its molecular weight may be obtained from the mass spectrum. However, the mass peak may not match to any known compound, substance, or, more specifically, to any known drug of abuse. As a result, there is a need for additional systems and methods to predict the mass spectra of unknown compounds and add them to a library or database of mass spectra so that compounds such as “designer” drugs of abuse can be quickly and automatically identified by laboratory instruments. LC-MS and LC-MS/MS Background Mass spectrometry (MS) is an analytical technique for the detection and quantitation of chemical compounds based on the analysis of mass-to-charge ratios (m/z) of ions formed from those compounds. The combination of mass spectrometry (MS) and liquid chromatography (LC) is an important analytical tool for the identification and quantitation of compounds within a mixture. Generally, in liquid chromatography, a fluid sample under analysis is passed through a column filled with a chemically-treated solid adsorbent material (typically in the form of small solid particles, e.g., silica). Due to slightly different interactions of components of the mixture with the solid adsorbent material (typically referred to as the stationary phase), the different components can have different transit (elution) times through the packed column, resulting in separation of the various components. Note that the terms “mass” and “m/z” are used interchangeably herein. One of ordinary skill in the art understands that a mass can be found from an m/z by multiplying the m/z by the charge. Similarly, the m/z can be found from a mass by dividing the mass by the charge. In LC-MS, the effluent exiting the LC column can be continuously subjected to MS analysis. The data from this analysis can be processed to generate an extracted ion chromatogram (XIC), which can depict detected ion intensity (a measure of the number of detected ions of one or more particular analytes) as a function of retention time. In MS analysis, an MS or precursor ion scan is performed at each interval of the separation for a mass range that includes the precursor ion. An MS scan includes the selection of a precursor ion or precursor ion range and mass analysis of the precursor ion or precursor ion range. In some cases, the LC effluent can be subjected to tandem mass spectrometry (or mass spectrometry/mass spectrometry MS/MS) for the identification of product ions corresponding to the peaks in the XIC. For example, the precursor ions can be selected based on their mass/charge ratio to be subjected to subsequent stages of mass analysis. For example, the selected precursor ions can be fragmented (e.g., via collision-induced dissociation), and the fragmented ions (product ions) can be analyzed via a subsequent stage of mass spectrometry. Fragmentation Techniques Background Electron-based dissociation (ExD), ultraviolet photodissociation (UVPD), infrared photodissociation (IRMPD), and collision-induced dissociation (CID) are often used as fragmentation techniques for tandem mass spectrometry (MS/MS). CID is the most conventional technique for dissociation in tandem mass spectrometers. ExD can include, but is not limited to, electron-induced dissociation (EID), electron impact excitation in organics (EIEIO), electron capture dissociation (ECD), or electron transfer dissociation (ETD). Tandem Mass Spectrometry or MS/MS Background Tandem mass spectrometry or MS/MS involves ionization of one or more compounds of interest from a sample, selection of one or more precursor ions of the one or more compounds, fragmentation of the one or more precursor ions int