Orbitrap Exploris MX Mass Detector

Post-translational modifications (PTMs) and process-induced modifications can occur during upstream and downstream bioprocessing, formulation, and storage. Any PTMs impacting safety or efficacy are critical quality attributes (CQAs) that must be monitored and controlled. Liquid chromatography mass spectrometry (LC-MS) MAM offers simultaneous, direct, site-specific identification and quantitation of a broad set of peptide CQAs. With the ability to replace multiple assays used during drug development and manufacturing, MAM can accelerate approvals, increase product and process knowledge, reduce development time, and reduce lot release assay cost and time.

The Orbitrap Exploris MX detector adds unprecedented simplicity, robustness, and HRAM-enabled confidence to MAM workflows. In addition to operational productivity, integrated Chromeleon CDS provides superior MS data-processing tools and comprehensive controls for regulated labs.

Why MAM?

Embraced by industry and regulatory leaders, MAM is key to the future of high-quality biotherapeutics. MAM adoption across all stages of development and manufacturing enables efficient and comprehensive understanding of processes and products by replacing many assays with one. Thermo Fisher Scientific has developed a fit-for-purpose MAM solution—now drug developers have the partner they need to aid them in deploying MAM.

Wide applicability

The enhanced Orbitrap Exploris MX-based MAM workflow is applicable for monitoring PTMs such as glycosylation, deamidation, oxidation, peptides for sequence confirmation, and glycan profiling.

High-sensitivity mass determination up to m/z 8000

With optional mass range up to m/z 8000 and HRAM data quality, the Orbitrap Exploris MX detector is the ideal choice for rapid, high-confidence molecular weight profiling, even for complex mAb glycoforms at low concentrations. Confirming the molecular weight of large intact proteins under native and denaturing conditions is essential to biotherapeutic production and QC.

Why analyze native proteins

Analysis under non-denaturing conditions allows characterization of proteins in their near-native biological states. Previously, obtaining this information required multi-step labor intensive isolation and purification. Using native MS, quality attributes can be directly assessed with minimal need for sample preparation, rapidly providing mass information for all proteins in a sample.

Chromeleon CDS streamlines molecular weight determination

The automated parameter optimizer makes it easy to obtain trusted results. Complementary deconvolution algorithms optimized for isotopically resolved and unresolved data provide accurate molecular weights for intact proteins, in both denaturing and native conditions, and at low abundances.

The Orbitrap Exploris MX detector is an ideal solution for sensitive and robust intact mass monitoring of oligonucleotide sequences and their low-level production related impurities. Compared to low-resolution instruments which only provide average molecular weight, HRAM data enables resolution of very closely related intact oligonucleotide sequences. Unlike software that relies on traditional peak picking algorithms, Xtract and ReSpect deconvolution algorithms implemented in BioPharma Finder software make use of the Sliding Window feature intact and provide mass deconvolution on a chromatographic time scale to identify failed oligonucleotide sequences and process related impurities, even at low levels or in poorly resolved chromatographic peaks.

Complexity, diversity, and size of oligonucleotides and potential impurities makes analyses challenging

HRAM LC-MS is the technique of choice due to its mass accuracy, reproducibility, robustness, sensitivity, and speed. HRAM capability is indispensable in verifying that an oligonucleotide has the expected molecular weight.

BioPharma Finder software uniquely handles oligonucleotide nomenclature and custom modifications

BioPharma Finder software provides an intuitive set of tools to support sequence modifications at each subunit of the oligonucleotide, including the nucleoside base, backbone linker, and 2’ ribose positions. Custom building blocks can easily be inserted into existing sequences or utilized for future sequence creation. Chemical modifications can also be created and searched to identify unexpected or variable modifications of the target sequence.