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Emerging Trends in Analytical R&D

In the pharmaceutical discovery space, many promising analytical trends have emerged and are now on the rise – and they will see increasing use in drug discovery in coming years. Here are several analytical techniques that have begun having an impact on pharmaceutical drug discovery and development:

  • Multi-Dimensional Liquid Chromatography
    While multi-dimensional liquid chromatography has long been used to analyze complex mixtures, it was generally considered very complex and somewhat impractical.

    In recent years, however, it’s been greatly simplified – thanks to instrument advances, development of theoretical concepts, and practical improvements in the technique. All of these variables have come together to transform it into a technology well-suited to impurity identification. The separation power is increased by processing the sample using several distinct separation mechanisms.

    Coupling of two forms of liquid chromatography can shorten conventional workflow, enabling both class and species separation at the same time – before tandem mass spectrometry detection. This kind of multidimensional approach is being used more and more, especially in comprehensive mode (LC x LC).

    A fully automated LC x LC-MS/MS system is validated on standard compounds and then used to characterize the sample. Using LC x LC for separation at the start renders the sample less complex before it enters the probe. More easily identified and quantified by mass spec, the sample also requires less clean-up procedures—noticeably boosting efficiency and saving time. Using tandem mass spectrometry allows greater selectivity, specificity, and structural information to be obtained.

  • Hyphenated Mass Spectrometric Techniques
    Another trend involves using hyphenated mass spectrometric techniques to analyze ultra-thin films for high throughput screening. An optimized TGA-GC-MS method allows thin films to be analyzed without having to pre-treat samples. The method is also sufficiently sensitive to point out slight differences in the thermal behavior of ultra-thin films.

    By examining living cells and organisms in a label-free, non-invasive way, coherent Raman scattering can map 3D distributions of small drug molecules. In addition to its role in molecular-based drug discovery, it can be used to build innovative drug delivery systems and even for quality control of finished products. For example, it has been used to assess the size distribution of API micro-particles and the homogeneity of the API distribution in a composite formulated tablet.

  • Inductively Coupled Plasma Mass Spectrometry (ICP-MS)
    ICP-MS
    is highly sensitive and well-suited to multi-element trace analysis and ultra-trace analysis, often at the parts-per-trillion level. Effective at revealing inorganic impurities in pharmaceuticals and their ingredients, it can also detect specific elemental migration of colored plastic packaging used for soft drinks.

    Research has also recently shown how multidimensional LC-GC-GC-GC-preparative chromatography can be used to quickly isolate highly pure volatile compounds. The four-dimensional system can collect high sample amounts in just a few runs, with a high level of purity. By replacing the matrix with organic pure solvent, the LC system injects higher sample volumes and increases collection of compounds with lower concentration.

  • Error Analysis
    To conduct error analysis, parameters of overlapping peaks can be determined by separating complex spectra into individual components. In a recent study, it was shown that using the derivative mode for curve-fitting works better than normal mode when dealing with a background that is not modeled.

    The errors in finding the maximum peak positions of the doublets were most sensitive to the noise. Boosting the additive noise increased the relative number of good-fitting models in both the normal and derivative modes, but the probability decreased. 

  • Semi-Micro Methacrylate Monolithic Columns
    To separate alkylbenzenes and proteins by reversed-phase liquid chromatography, semi-micro methacrylate monolithic columns can be used. This is especially useful for separating proteins, as a recent study showed protein separation in all types of columns tested, although the efficiency differed.
  • LC/NMR/MS Integration
    Fully integrated LC/NMR/MS systems
    are critical to pharmaceutical bioanalysis. They harness the power of mass spectrometry’s rapid and ultra-sensitive screening capabilities to identify peaks of interest in complex mixtures for further analysis by NMR. Knowing which peak to submit to extended 1D or 2D NMR analysis makes chromatographic separation as efficient as possible.
  • Supercritical Fluid Chromatography (SFC)
    SFC is ideal for isolating impurities or purifying enantiomers, as it is faster, uses much less solvent, and is less expensive than HPLC. By showing itself to be a better, greener alternative, SFC will become even more popular in the years to come.

What are you seeing as trends in analytical R&D, and what do you hope will emerge in the future?

 

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