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Drug Discovery


The mass spectrometry innovations simplifying drug discovery workflows


Mass spectrometry (MS) has long been a valuable tool for drug discovery, and steady advances in its capabilities and performance have generated powerful insights for the pharmaceutical industry. The latest MS innovations are now helping biotherapeutics developers overcome challenges around sample preparation and large molecule analysis.


By Helen


Stewart-Miller and Dr Richard Massey


T


he use of MS in pharmaceutical discovery and development is rich and varied, span- ning a wealth of applications from target


discovery, medicinal chemistry, pharmacokinetics and bioanalysis workflows, to name just a few. Offering the selectivity, specificity and sensitivity required to answer a broad range of analytical questions, MS has become one of the most power- ful tools in the drug discovery toolbox. While the traditional coupling of MS with liquid chromatog- raphy (LC) and gas chromatography (GC) contin- ues to be a robust method, technological advances have seen the rise of other techniques, such as matrix-assisted laser desorption (MALDI) being directly coupled with MS, making it adept for even more applications. For example, the latest MS technologies can simultaneously analyse many fea- tures in one cell, which could help researchers dis- cover novel targets with the potential for transla- tion into new therapies. MS is a particularly powerful tool for the discov-


ery and development of biotherapeutics. Today, biotherapeutic products account for a growing proportion of new drug approvals. Increased focus on the development of much larger, more complex therapeutics such as monoclonal antibodies, fusion proteins and antibody-drug conjugates has placed


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new demands on MS. While small molecule drugs can easily be analysed on a system with a mass range of 1,250 Daltons (Da), the analysis of higher order structures such as peptides, proteins and oligonucleotides can require the visualisation of ions from the 2,000 Da to the tens of thousands of Da range. This increased molecular complexity means that


much greater instrument resolution is required to confidently elucidate atomic-level structure and func- tion. Where a single or triple quadrupole mass spec- trometer offering unit-mass resolution may be suffi- cient for early metabolite, impurity and degradant screening, high resolution accurate mass (HRAM) has become increasingly important for the analysis of large biotherapeutics and protein complexes. “The evolution of mass analysers to acquire high


resolution data at high mass ranges, in time frames amenable to coupling with ultra-high performance LC (UHPLC) has been incredibly important for drug discovery efforts,” says Rowan Moore, Senior Manager of the European Pharma and BioPharma Customer Solutions Center at Thermo Fisher Scientific. “The commercialisation of mass spectrometers with high mass, high resolving capa- bilities has undoubtedly opened new avenues in the study of protein drugs and their targets.”


Drug Discovery World Summer 2018


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