From Research to Routine
The needs of the pharma industry are always evolving – and analytical techniques must advance to remain relevant or adapt to fulfill new demands. Here, I describe how mass data is marching from R&D into more routine use: the search for genotoxic impurities.
Moosung Kim |
sponsored by Waters
Daewoong Pharmaceuticals has seen countless analytical advances over the years. Founded in 1945 as a global healthcare company, it is one of the top ten largest drug companies in South Korea and regarded as a pharmaceutical “giant”. In addition to its significant South Korean footprint, Daewoong’s ongoing research into new drugs, generics and biosimilars is supported by its laboratories in the US, India and China.
As well as being essential for an increasingly global business, our laboratories around the world allow us to collaborate internationally on research that accelerates technological development. Daewoong's core value of “open collaboration” goes beyond our employees. In fact, we take the concept a step further by opening our research facilities to everyone – even external researchers. Accordingly, we also cooperate with professors from other institutes and also other laboratories.
Currently, liquid and gas chromatography represent our workhorse separation techniques – they’ve been in use for over 16 years – and we introduced mass spectrometry in around 2002. Over the years, we have invested heavily in the instrumentation necessary to create an environment where internal and external collaborators can flourish; keeping up to date with advances in chromatography, spectroscopy and mass spectrometry also ensures that we remain successful in a competitive market.
Analytical stepping stones – and the power of mass detection
In the early days, our analytical work was closely tied to the development of quality generic raw material for export. In more recent years, we needed to develop analytical methods for new drugs and raw materials. Now, we are focusing on trace and structural analysis – a trend that demanded an expansion of my own scope of expertise into mass measurement.
Specifically, in my role of Senior Research Fellow in our new drug development center in R&D, I work for CMC (Chemistry, Manufacturing and Control), developing new drugs and managing CMC involvement in discovery, development, QA/QC and regulatory affairs.
Today, mass detection plays an essential role in our analytical workflows – and there are several general advantages that newcomers to the technology may be unaware of. Here, I present four points – some specific to the Waters ACQUITY QDa mass detector – that are particularly worth noting:
- Perhaps the biggest advantage is that mass detection allows both qualitative and quantitative analysis. Qualitative experimental modes on ACQUITY QDa facilitate faster method development of API impurity methods – identification of co-elutions and method confidence, for example. And the quantitative experimental mode – single ion recording (SIR) – allows quantitation at lower limits of detection than typical optical detection, but comparable to legacy MS systems (1).
- The mass detector is more “universal” in operation – in other words, because detection is based on specific mass measurements, it can detect many substances – even at trace amounts – without concerns for the need of other attributes, such as the presence of chromophores or specific volatility.
- A special stand-out feature of the QDa is ease of use. After focused training for a day – or even less – almost anyone can operate the instrument. This is a game changer in terms of mass data accessibility. Though I should add a caveat: data analysis can still be a challenge when working with unknown or impure compounds.
- More specific to the QDa: the price point relative to legacy single quadrupole mass spectrometers has dropped considerably. Today, gaining access to the advantages highlighted in i) and ii) above no longer requires such a substantial investment in both capital equipment and resources.
Making mass detection routine
It is important to note that regulations, such as the guidelines issued by ICH (2), have also driven our technology choices. Today, whenever new medicines are approved, compounds must undergo early inspection to detect foreign substances – and the data must be stored, even when submission of a report is not required. Therefore, the pharma industry requires sensitive instrumentation that can detect trace amounts of contaminating compounds in routine workflows, which is why, alongside the other benefits previously described, we switched from our legacy single quadrupole mass spectrometers to the QDa mass detector.
Previously, when mass spectrometry was primarily used in research, efficiency and ease of use were not high on the agenda. But the new demand for mass data in official documents for approval or quality control has really emphasized the need for rapid reporting and user-friendliness. In quality control, SIR mode is typically used – and that’s where QDa comes into its own, offering fast turnaround of quantitative analyses.
When it comes to genotoxic impurity (GTI) analysis, for example, the ACQUITY QDa offers rapid, accurate – and reproducible – analyte quantitation. Here, the use of mass detection with SIR boosts specificity and sensitivity, both of which are essential given the low concentrations of impurities being quantified.
In the past, such analyses would have typically demanded triple quadrupole MS methods that could only be commissioned from a dedicated analytical laboratory – and would result in additional expense and necessitate the cumbersome process of checking equipment availability. Now, as the chromatographers have access to a mass detector, we can mostly perform this analysis ourselves. Direct analysis means time saved – and decisions can be made more efficiently.
Mass detection in pharma’s future
Accessibility to mass data is now at the point where it meets new demands in pharmaceutical analysis. By combining sensitivity, functionality, robustness, and chromatography data system (CDS) familiarity in such a user-friendly system, mass data can finally move out of research and specialist analytical laboratories and take on a quality control role in manufacturing.
I believe mass detectors like the ACQUITY QDa will continue to gain traction where the routine use of mass data complements more traditional methods – or where it boosts productivity by reducing the need to send samples to a dedicated mass spectrometry facility.
- M Maziarz, M Wrona, “Coupling mass detection with UV to improve method sensitivity for esters of benzenesulfonic acid in analysis of genotoxic impurities”. Available at: bit.ly/2qYcdrV. Accessed May 9, 2017.
- ICH, “Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk”, (2014). Available at: bit.ly/1vgSDCe. Accessed May 9, 2017.