The benefits of high-resolution mass spectrometry for impurity profiling

Author: Chris Nortcliffe, Mass Spectrometry Manager

The growing complexity of pharmaceuticals has resulted in increasingly complex impurity profiles. This, coupled with the use of diverse starting materials and evolving regulatory requirements around impurity detection, has introduced new analytical challenges to impurity profiling. Meanwhile, technological advancements, including higher resolution mass analysers, have increased the sensitivity and speed of mass spectrometry, making it a powerful technique for impurity profiling. Pharmaceutical organisations can utilise these tools to meet regulatory requirements while also bringing new efficiency to their programme.

I recently penned a whitepaper about a specific analysis strategy to assess and identify impurities within a model system of a triazine pesticide using mass spectrometry (MS) and tandem mass spectrometry (MS/MS). If you haven’t read it, you can access the full paper here.

While MS is a powerful tool for impurity profiling, the key to employing it successfully is knowing when to harness it based on the impurity types and analytical requirements of your unique application. In this blog, we’ll discuss some of the advantages of MS and MS/MS over other techniques like thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC), and identify scenarios in which MS and MS/MS are the optimal impurity profiling approach.

Comparing mass spectrometry and tandem mass spectrometry to thin-layer chromatography and high-performance liquid chromatography

Mass spectrometry provides greater sensitivity and selectivity than techniques like thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC), enabling the detection of trace impurities and reducing interferences in impurity profiling. In addition to its sensitivity and selectivity benefits, mass spec sheds light on structural information which cannot be provided by these other techniques—a key advantage when it comes to impurity profiling.

More specifically, TLC is largely a qualitative technique and lacks scalable quantitative data that can be used for analysis. In addition, TLC lacks resolution compared to mass spectrometry, which can result in inaccuracy, and provides no additional structural information.

HPLC also provides limited structural insight and is often combined with other techniques to fill this gap. Furthermore, HPLC falls short when it comes to the length of the process, which can be quite long, making it less ideal in certain situations amid a desire for accelerated project timelines.

An additional benefit of MS over HPLC in particular is that chromatographic resolution of peaks in the trace is important. It can sometimes be difficult to resolve close running peaks from one another, and easy to miss peaks that co-elute. MS has the advantage of detecting even small mass differences between species that may otherwise co-elute on a HPLC trace, saving valuable analytical development time

When is mass spectrometry the right choice for impurity profiling?

Mass spectrometry and tandem mass spectrometry offer deeper levels of structural information, specificity and speed compared to some of the most widely used impurity profiling techniques, with a trade-off of increased sample preparation and cost. It also utilises far less sample than orthogonal techniques. By understanding the applications for which these analytical approaches are best suited, we can maximise the benefits of these techniques for our customers.

Mass spectrometry can be especially valuable in scenarios where impurities are unknown, as it can aid in identifying impurities even in complex mixtures. Its ability to provide precise information on low-level impurity substructures is a powerful tool in identification and characterisation. High-resolution mass spectrometry, in particular, can deliver mass data across several orders of magnitude, enabling scientists to observe isotope and fragmentation patterns to match the observed information of potential structures or isomers.

Due to their exceedingly high levels of sensitivity, these methods also prove extremely valuable in monitoring scenarios to ensure rigorous quality and compliance standards are met. The techniques are similarly powerful in stability analysis, in which impurities are analysed under a variety of conditions.

Finally, mass spec is particularly useful in high-throughput scenarios, as it enables rapid analysis when used both on its own and in conjunction with other analytical techniques.

Optimising impurity profiling with the right partner

As analytical technologies continue to advance, impurity profiling techniques will naturally continue to evolve. With so many alternative techniques at our disposal, the role of an innovative and highly experienced partner has never been more important.

At Sterling, we bring more than 50 years’ of experience in full-service API development and manufacturing services, including extensive experience in analytical chemistry and impurity characterisation. To speak with an expert about the unique impurity profiling requirements of your project, contact us here.