Drug Discovery
barriers that can increase timelines, not only for high-value activities such as tissue imaging, but also for purity assessment and confirmation of identity in medicinal chemistry synthesis too,” says Plumb. With the average time to market for most therapies being around a decade (and cost- ing upwards of $1 billion), innovations such as these are playing an important role in accelerating the delivery of new therapies to the patients who need them. In addition to the challenge of sample prepara-
tion in bioanalysis workflows is the increased chemical background of biological samples. “Matrix interference adds a complexity to the analysis which means we then have to look at addi- tional innovations,” says Neil Walsh, Global Marketing Manager, Pharma/CRO at SCIEX. Here, the use of technologies such as differential mobility spectrometry and capillary electrophore- sis MS (CE-MS) is allowing researchers to push the boundaries when it comes to generating meaning- ful analyses from complex samples. Differential mobility spectrometry (DMS) has
proven to be a valuable addition to ion mobility spectrometry methods, providing separations that are orthogonal to traditional LC-MS workflows. The technique makes use of a fast gas stream at right angles to an electric field, which causes ions of different mobilities to pass through the instru- ment with different trajectories1. The use of DMS can sometimes circumvent the need to use LC tech- niques, due to its ability to provide reduced isobar- ic and isomeric chemical noise, without the need for extensive sample preparation steps. As a result,
it is considered to be a powerful approach for bio- analysis workflows. CE-MS is a powerful analytical technique that
combines the high separation efficiency of capillary electrophoresis with the detailed characterisation that can be achieved using MS or HRAM analy- sis2. As the method allows the analysis of intact proteins and various small molecules, including peptides, CE-MS is helping researchers obtain answers to questions that would not otherwise be possible using conventional LC techniques. “These technologies are real milestones for
orthogonal techniques,” says Walsh. “Their appli- cation is truly helping researchers overcome com- plex challenges, especially those relating to difficult to analyse sample matrices.”
Commercially-available MS technologies A wide range of products are available on the mar- ket that are reducing the complexities associated with drug discovery workflows. SCIEX offers instruments for the confident char-
acterisation of both small and large molecule thera- peutics. Its latest TripleTOF® 6600 Quadrupole Time-Of-Flight (QTOF) mass analyser, for example, enables additional insights for more complex sam- ples through its single multifaceted platform. The ability to perform data-independent SWATH® (sequential window acquisition of all theoretical fragment ion spectra) allows the collection of com- prehensive high-resolution MS data for every detectable analyte. The system also allows for large numbers of Q1 isolation windows at user-controlled
Figure 2 Advances in MS are giving scientists new insights for more complex samples that are opening new opportunities for drug discovery
Drug Discovery World Summer 2018
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