Industry: Pharmaceutical
Instrument: HT3 Static and Dynamic Headspace System
Developing One Universal Method for Residual Solvents Using the New Teledyne Tekmar HT3™ Headspace Sample Introduction System
A variety of solvents are used in the manufacturing of pharmaceutical products, substances, and excipients. In an effort to protect the health of the patient, pharmaceutical companies are adopting methodologies that will reduce the toxicity of the residual solvents. The International Conference on Harmonization (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use has published guidelines on a list of 3 separate classes of residual solvents and their daily exposure limits.
Class 1. These residual solvents are know carcinogens or environmental hazards and are avoided whenever possible in pharmaceutical manufacturing.
Class 2. This class causes some reversible or irreversible toxicity but is less toxic than class 1. These solvents are limited in their use in pharmaceutical manufacturing.
Class 3. These residual solvents have a low toxic potential or have no health-related exposure limits.
Difficulties have occurred in finding a matrix in which all of the residual solvents can be successfully analyzed. The diversity of pharmaceutical matrices has produced many analytical methods for the analysis of residual solvents. The multitude of methods has created a significant cost and complexity barrier to establishing residual solvent compliance on a global basis. Recently, a universal analytical method was developed using 1,3-dimethyl-2-imidazolidinone (DMI) as the sample matrix for the dissolution of the drug compounds with the use of static headspace for sample introduction into a Gas Chromatograph (GC).
DMI provides good solubility characteristics for a broad range of drug compounds. DMI is thermally stable and can be obtained at high purities (example 99.5%). DMI has the capability to dissolve both organic and inorganic compounds. The solubility characteristics allow for many drug substances and residual solvents to be evaluated using one method instead of numerous methods.
The static headspace sample introduction technique allows residual solvents in DMI to diffuse into a gas phase within a sealed vial until equilibrium is reached. The gas phase is then transferred to the GC for analysis. Because the sample transferred to the GC is in a gas phase, there is minimal interference from drug substance and drug product excipients.
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