Methods & Technologies / Residual Solvents

Applications for Residual Solvents


Analysis of Residual Solvents in Pharmaceuticals Using Headspace GC-FID/MS Detector Splitting System

Headspace gas chromatography with flame ionization detection (GC-FID) is often used for residual solvent testing of pharmaceuticals, though the qualitative power of this method is not particularly high. Because gas chromatography mass spectrometry (GC/MS) utilizes MS to perform qualitative analysis based on mass spectra, GC/MS can be used to estimate and identify individual peaks detected in the expected vicinity of a target solvent as well as other unknown peaks.

We describe an example of residual solvent test of a pharmaceutical using a detector splitting system that simultaneously obtains FID and MS data in a single measurement.


Analysis of Residual Solvents in Pharmaceuticals  - An Analysis Method for Class 2 Solvents (Water- Soluble Samples) Unsuited to Headspace GC Methods

Testing methods for residual solvents in pharmaceuticals are defined in the Japanese Pharmacopoeia Seventeenth Edition and USP (U.S. Pharmacopeia), General Chapters <467> Residual Solvents. While these testing methods mainly describe the detailed testing procedures for Class 1 and Class 2 residual solvents using headspace GC methods, there is no mention of testing methods for solvents possibly used in the testing of compounds and water-insoluble pharmaceuticals, which are unsuited to headspace analysis.


Using GCMS to Test for Residual Solvents in Pharmaceuticals

The HS-GC-FID method is used to test for residual solvents in pharmaceuticals, but GC-MS is useful for identifying peaks in close proximity or for qualifying unknown peaks. However, to qualify peaks detected by GC-FID using GC-MS requires matching chromatogram patterns. The advanced flow controller (AFC) in GC-2010 Plus systems includes constant linear velocity control as standard functionality. This allows achieving similar retention time and separation patterns in GC-FID and GC-MS chromatograms by specifying the same linear velocity setting, provided the columns are identical or columns with the same phase ratio are used.


GCMS Solutions for Pharmaceuticals

The headspace-GC (FID) method specified in the Japanese Pharmacopoeia is normally used to test for residual solvents in pharmaceuticals. However, unknown peaks not from target solvents sometimes appear during testing. GC-MS can be useful for qualitatively analyzing those peaks. Since GC-MS systems can be equipped with an FID detector, the same system can be used for both GC-MS and GC Analysis.

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