News from LabRulezLCMS Library - Week 45, 2024

Our Library never stops expanding. What are the most recent contributions to LabRulezLCMS Library in the week of 4th November 2024? Check out new documents from the field of liquid phase, especially HPLC and LC/MS techniques!

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This week we bring you posters, applications, and technical notes by Thermo Fisher Scientific, Shimadzu, Waters Corporation, and Agilent Technologies!

1. Thermo Fisher Scientific: Confident transformation site localization of PROTAC drug metabolites facilitated by multi-stage fragmentation LC-MS

• poster (ASMS)

Abstract

Purpose: Confident characterization of PROTAC drug metabolites for transformation site localization and soft-spot analysis.

Methods: Drug metabolites were analyzed using MSn fragmentation data acquisition on a Thermo Scientific Orbitrap Ascend Biopharma Tribrid mass spectrometer and data interpretation in Thermo Scientific Compound Discoverer 3.3 SP3 software. Results: PROTAC drug metabolism was found to be extensive for the investigated compounds. Among the detected metabolites, several isomeric compounds were found where MSn fragmentation data could be used to reduce ambiguity in the transformation site localization, especially for metabolites with higher molecular weights.

Introduction

The study of a drug’s metabolism is an integral part of drug discovery and development, from improving drug exposure to flagging potential toxicity from its metabolites. The identification of drug metabolites routinely relies on LC/MS experiments, with fragmentation data enabling their structure elucidation. In recent years, hetero-bifunctional small molecule drugs, acting on a given protein of interest (POI) through recruitment of inherent protein degradation pathways rather than inhibition, have gained significant interest as new modalities, with multiple such proteolysis targeting chimera (PROTAC®) drug candidates being investigated in clinical trials.[1] However, due to PROTAC’s unique properties, the identification of their metabolites can be challenging.[2] Here, we describe the utility of multi-stage fragmentation (MSn) for the elucidation of transformation sites on PROTAC drug metabolites, based on analysis of the representative compounds shown in Figure 2.

Conclusions

• The utility of flexible MS data acquisition methods for metabolite identification could be demonstrated with two representative PROTAC compounds, MZ1 and dBET1, which exhibit extensive metabolism in vitro.
• MSn fragmentation data helped to enhance the precision of transformation site localization, particularly for isomeric metabolites and those with high molecular weights.

2. Shimadzu: Automatic Optimization of Gradient Conditions by AI Algorithm for Impurity Analysis

• Application

User Benefits

• The AI algorithm of LabSolutions MD can automatically optimize gradient conditions to greatly reduce labor of LC method development.
• Anyone can optimize gradient conditions, regardless of their experience in chromatography.
• Gradient conditions that meet the resolution criteria for specified peaks are automatically searched (e.g., principal component and its related impurities).

Introduction

In the typical LC method development, the process begins with “preparation” which includes mobile phase preparation, column installation, and creation of analysis schedules, then the analysis is started. After that, the acquired data is analyzed and “preparation” for the subsequent analysis is carried out, followed by starting the next analysis again. The method development progresses by repeating these processes, but in addition to the significant time required to repeatedly create analysis schedules, expertise in chromatography is necessary to explore optimal conditions based on data analysis. In other words, typical method development requires “human intervention”. Therefore, eliminating human involvement and automating such method development processes would be desirable to improve labor efficiency. This article introduces an example of automatic optimization of gradient conditions to separate montelukast (a small molecule drug) and its related impurities using LabSolutions MD (Technical Report C190-E309), a dedicated software for supporting method development.

Conclusion

Automatic optimization of gradient conditions using AI algorithm of LabSolutions MD was applied to montelukast and its related impurity. As a result, gradient conditions that met the criteria (“resolution for montelukast and related impurity > 3.0” and “elution time of the last peak < 15 minutes”) were successfully explored. This result indicates that significant labor saving in method development can be expected by LabSolutions MD. This article introduces an automatic optimization of gradient conditions in method development while LabSolutions MD also supports a series of workflow of method development, including the screening phase and robustness evaluation phase. For details, please refer to the Technical Report “Efficient Method Development Based on Analytical Quality by Design with LabSolutions MD Software (C190-E284)”.

3. Agilent Technologies: Agilent InfinityLab Assist: A Local User Interface to Control and Automate Your HPLC System (Infinity III)

• Technical note

Abstract

Modern liquid chromatography (LC) instruments rely on a permanent connection to a PC that runs the chromatography data system (CDS) and provides a comprehensive set of controls and instrument diagnostics. In large laboratories, the CDS is often set up as a client/server system, composed of a central data storage (server) and multiple PCs (clients) that can in turn control multiple LC instruments. This setup makes it harder for users to control the LC and monitor what is happening with the instrument at the same time. Adding a tablet-style user interface to each LC solves this issue by bringing important controls and diagnostics to the user’s fingertips right at the instrument. The Agilent InfinityLab Assist not only fulfills these functions, but also incorporates automated, guided, and scheduled features that enable the user to perform daily tasks easier, faster, and with increased confidence.

Introduction

Laboratories with many different analytical instruments often have their instruments connected to a central data system that allows sample submission and data analysis from a remote PC. Using an Agilent OpenLab client/server system, multiple instruments can be controlled from a single client or Agilent Instrument Controller, which is not necessarily located at the same bench, or even in the same room as the instrument. This setup might be advantageous with respect to safety and optimal use of lab space. Tasks that require interaction with both the instrument and the controlling PC, however, become more tedious and error-prone if the user needs to swap positions constantly. A local user interface resolves this issue and adds confidence and convenience to instrument control. This white paper describes how typical laboratory workflows benefit from InfinityLab Assist, a module that adds local control and automation to any InfinityLab LC system.*

*_{The Agilent InfinityLab Assist is compatible with Agilent 1260 Infinity II LC, Agilent 1260 Infinity III LC, Agilent 1290 Infinity II LC, and Agilent 1290 Infinity III LC systems}

Conclusion

The Agilent InfinityLab Assist is the direct interactive access point to control Agilent InfinityLab LC systems. Monitoring instrument actuals, setting
system parameters, and executing daily tasks such as purging are accessible through an adjustable multitouch display at the instrument. Automated tasks to equilibrate the system or to induce a standby can be customized, saved, and scheduled on-demand. Integrated guides for maintenance and troubleshooting facilitate these tasks and, if required, point the user to the solution without the need to consult external documentation. These features make daily laboratory work faster, easier, and less error-prone, even for inexperienced users, and thus help labs act more efficiently and economically.

4. Waters Corporation: CONVERSION AND INTEGRATION OF OMICS DATA FROM A PROTOTYPE, BENCHTOP MULTI-REFLECTING TIME-OF-FLIGHT (MRT) PLATFORM WITH THIRD-PARTY INFORMATIC WORKFLOWS

• Poster (ASMS)

INTRODUCTION

OMIC studies typically generate large and complex data sets, derived from various sample types such as biofluids. As mass spectrometry (MS) technology rapidly advances and with data acquisition methods such as data independent analysis (DIA) progressing, the ability to delve deeper into the metabolome and lipidome is significantly improved, whilst at the same time generating high-dimensional datasets. In this study, we describe a data processing pipeline which converts MS data (DIA and DDA based) that were collected using a novel, multi-reflecting ToF mass spectrometry into a generic file format, that can be readily processed by a variety of third-party informatic tools. Data were primarily processed via Skyline1 and MS-Dial2 for lipidomic datasets, whilst metabolomic datasets were processed using XCMS3.

CONCLUSION

• Data Convert provides a flexible and easy approach to generating mzML files from DDA and DIA acquisitions.
• Integration of Data Convert into waters_connect allows a seamless workflow of automatically generating mzML during data acquisition, in addition to having flexibility for users to export mzML from projects at any point in time.
• mzML files can be tailored for the intended third party informatics package (i.e., centroided, compressed etc).
• Data from the benchtop Xevo MRT has demonstrated the workflow from data acquisition through to data processing with third party tools, such as Skyline, MS-Dial and XCMS using the waters_connect/Data Convert pipeline.
• Metabolomic and lipidomic datasets highlight the high quality data that can be generated from the Xevo MRT mass spectrometer:
  • Superior mass accuracy (sub 1 ppm)
  • High mass resolution which can be maintained with fast, high throughput LC gradients
  • High levels of sensitivity/dynamic range