A New Method for Fast Residual Solvents Analysis and Untargeted Unknown Identification
Faster Sample Throughput and Shorter GC Runtimes Using GC-VUV and Static Headspace
Volatile organic compounds are used in pharmaceutical manufacturing during the production of drug substances, pharmaceutical additives, and drug products. Known also as residual solvents, they account for 50-90% of mass in typical pharmaceutical operations and represent most of the process toxicity. These organic solvents can contaminate the drug product during its packaging, storage, and transportation. Testing for the presence of these solvents in Active Pharmaceutical Ingredients (API) is critical for patient safety and commonly follows Unites States Pharmacopeia (USP) Method <467> guidelines, or more broadly, International Council for Harmonization (ICH) Guideline Q3C(R6).
USP Method <467> recommends a 60-minute gas chromatography (GC) runtime for residual solvent analysis . Class 1 and 2 solvents are additionally suggested to be analysed separately. VUV Analytics recently published an application note describing how the spectral deconvolution capabilities of VUV spectroscopy allow GC runtimes to be shortened from 60 minutes to 10 minutes or less . Solvent classes can also be combined into individual analyses for increased sample throughput.
GC-VUV spectral data is inherently three dimensional (time, absorbance, wavelength) and specific to compound chemical structure. Most compounds absorb strongly in the VUV region (120 – 240 nm) of the UV spectrum measured by VUV detection. Photons in this wavelength range are capable of producing electronic transitions in virtually all chemical bonds, especially in ground state to excited state transitions such as σ→σ* and π→π*. The result is spectral signatures that are specific to each compound and can be readily identified by the VUV library3. This characteristic of VUV spectroscopy lends itself to intentional chromatographic compression due to the ability to deconvolve overlapping spectral responses.
A GC-VUV method that utilises static headspace sampling was developed for the analysis of all residual solvent classes (Class 1 – 3), as well as other solvents of interest. Significant gains in analysis productivity can be realised by decreasing total GC runtimes by greater than 5X. This capability is demonstrated here by condensing the runtime used in Class 3 residual solvent analysis. The GC-VUV method…