Agilent 6560 Ion Mobility LC/Q-TOF System Upgrade

Background DPQR is requesting a suite of hardware and software updates to our Agilent 6560B ion mobility high resolution quadrupole time-of-flight mass spectrometer (IM-QTOF) platform to address the increasing regulatory research needs and sample testing requests for the evaluation of complex pharmaceutical drug products, e.g. complex generics, biosimilars, and emerging drug entities.

Mass spectrometry is a tool for measuring molecular mass information of various types of drug products: small molecules, peptides, proteins, oligonucleotides, etc. Recent advances of integrating ion mobility with mass spectrometry provides additional information regarding the analytes’ gas phase collision cross section (CCS) which can be used to infer various structural information of the analyte as well as possible isomer identification.

Advanced ion mobility techniques such as collision-induced unfolding (CIU) can be further used to monitor the conformational dynamics of biomolecules and gain insight into their higher-order structure (HOS). The regulatory evaluation from the perspectives of product characterization, quality control, and sameness or similarity assessment for complex pharmaceutical products has always been challenging due to their complex structure and/or impurity profile.

It is critical that the FDA laboratories have the facility and capability to fully characterize the complex drug products which helps address the regulatory inquires and concerns during the review process. Currently, DPQR has an instrument platform consisting of an Agilent 6560B IM-QTOF system connected to an Agilent RapidFire 365 robotic sampling platform.

We aim to upgrade the current platform by incorporating a CIU activation cell to our 6560 system and a biologic compatible high performance liquid chromatography system, enabling advanced separation prior to mass spectrometry analysis, through a hardware upgrade as well as software upgrade for interpreting advanced ion mobility mass spectrometry data.

This platform will advance DPQR’s analytical capability and research readiness to generate critical evidence to support both new, generic, and biosimilar drug applications. Scope To obtain a software and hardware upgrade to the existing Agilent 6560B IM-QTOP System Requirement Contractor shall provide the following salient characteristics to the Agilent 6560B IM-QTOP upgrade:

Item 1: Instrument -A hardware upgrade to the Agilent 6560B IM-QTOF instrument allowing for collision-induced unfolding (CIU) capabilities for ions, such as antibodies (MW 150 kDa), from native to their extended conformation states.

This upgrade should be fully compatible, both hardware and software, to existing Agilent 6560B platform instrumentation and should not introduce any detriment to instrument capacity. -An ultra performance liquid chromatography (UPLC) system that is biocompatible, have a binary system (1300bar), thermally controlled multiplate sampler (4 C to 40 C) and column compartment (4 C to 60 C), variable wavelength detector, and flex bench mobile cart for easy movement.

This UPLC system must be fully compatible, both hardware and software, to existing Agilent 6560B platform instrumentation and easy to swap in/out with the currently linked Agilent RapidFire 365 system. -Required source ion optic hardware needed for analysis of peptide, proteins, antibodies, and oligonucleotides.

Item 2: Software -Software that is compatible with data generated from the upgraded Agilent 6560B and purchased UPLC system to allow for data/library management, targeted/non-targeted analysis, peptide/protein analysis, oligonucleotide analysis, compound discovery, etc.