Improving the Analysis of Organic Volatile Impurities in Pharmaceuticals

Organic solvents are widely used in the manufacture of active pharmaceuticals and other drug products. Many can enhance production yields, improve crystallization or increase solubility, but are potentially toxic to humans or harmful to the environment. To safeguard the public, regulations in most countries limit the levels of organic volatile impurities (OVIs) that can be present in finished pharmaceutical products.

In recent years, the accepted safe levels of OVIs and other contaminants have trended downward due to both new information regarding toxicity and new analytical capabilities. Over time, researchers and regulatory agencies have learned more about the potential harmful effects of long-term and low-level exposure to residual solvents. Their work has been aided by improvements in the detection sensitivity of analytical instrumentation.

Detecting low-level impurities

Most quality control labs in pharmaceutical manufacturing use gas chromatography (GC) for the analysis of OVIs. GC coupled with headspace sampling (HS) is acknowledged as an easy-to-use, high-throughput tool for determination of these low-level impurities.

A recent Agilent application note describes results produced by an enhanced system that combines HS, GC and mass-selective detection (MSD) to provide compound identification, confirmation and quantitation. The system included the Agilent G1888 network headspace sampler interfaced to a 6890N GC and configured with a 5975 inert MSD. The system also included the MSD Productivity ChemStation software. For regulated laboratories, the MSD Security ChemStation software provides the same functionality plus the ability to work in full compliance with 21 CFR Part 11.

Enabling dual analyses

The methods and procedures outlined in the application note illustrate new potential approaches to the analysis of residual solvents by HS/GC/MSD. The key enabler is the latest version of the 5975 inert MSD: its Synchronous SIM/Scan operating mode provides library searchable full-scan spectra as well as trace-level selected ion monitoring (SIM) data in the same acquisition. The companion AutoSIM function automatically converts full-scan data into SIM acquisition parameters for use in Synchronous SIM/Scan methods.

With these capabilities complementing the excellent sensitivity of the HS/GC/MSD system, manufacturers of pharmaceuticals can more easily ensure that OVIs and related contaminants are either absent from their products or are present below accepted safe levels.

For more information

To learn more about related solutions, please see the Drug Manufacturing/QA/QC page. For additional information about these and other Agilent chemical analysis products and resources, please visit the Life Sciences/Chemical Analysis main page.