Blog Post 9 – Through the Lens of GC/QTOF: Tracking Down Impurities in Ophthalmics
3 min reading time
In the development of ophthalmic drug products, impurity profiling is essential to ensure long-term safety and regulatory compliance. While many impurities are well-characterized, unexpected compounds can emerge—particularly after formulation changes—requiring a flexible and multi-technique analytical approach.
In this case, the customer detected a previously unobserved impurity during a new stability study, initiated after a change in the formulation.
Initial identification efforts were conducted using our high-end Liquid Chromatography Mass Spectrometry (LC/MS) platform, applying high-resolution mass spectrometry to characterize the unknown peak. Despite method optimization and trials with multiple ionization techniques, no MS signal was observed at the retention time of the UV-detected peak. This suggested that the compound was either too volatile, too non-polar, or otherwise incompatible with LC/MS detection.
Figure 1: Overview of the different steps taken in the detection and identification process
To address this, a solvent switch to an organic solvent was performed, enabling analysis on our Gas Chromatography Quadrupole Time-of-Flight (GC/QTOF) platform. This approach allowed a successful detection of the impurity. The retention time and mass spectrum of the impurity was searched in our Nelson Lab’s proprietary Screener Database of Semi-Volatile Organic Compounds (SVOC) and yielded one excellent match. This compound is a known preservative commonly used in ophthalmic products.
To confirm the result, a reference standard of the identified compound was prepared and analyzed using our LC/UV system. The retention time and UV spectrum matched those of the original impurity peak, thereby validating the identification.
This case illustrates the importance of combining orthogonal analytical techniques and using comprehensive compound databases. The inability of LC/MS to detect the impurity demonstrates the value of GC-based methods for volatile and semi-volatile compounds. By integrating GC/QTOF analysis with database-driven identification and LC/UV confirmation, a robust impurity characterization was achieved.
At Nelson Labs, we specialize in resolving complex impurity challenges through advanced instrumentation, rapid method adaptation, and deep domain expertise. Our multi-platform capabilities and extensive databases enable us to support clients in maintaining the highest standards of pharmaceutical quality—especially in sensitive applications like ophthalmic drug products.
If you have additional questions about Impurities Identification test services or would like to consult with the experts at Nelson Labs, just send an e-mail to [email protected].
