Safety of pharmaceuticals is paramount as even small amounts of impurities can influence the safety and efficacy of a pharmaceutical product. Because of this reason, governmental drug regulatory bodies, such as the U.S. Food and Drug Administration (FDA), require pharma manufacturers to verify the identity, strength, quality, and purity characteristics of pharma products.
Iimpurities are defined as any component of the active pharmaceutical ingredient (API) that is not the chemical entity defined as the API.1 (as per the International Conference on Harmonization). Therefore, the identification, quantification, and control of impurities are important during drug development in the pharmaceutical industry.
A primary consideration in the development of a suitable ion chromatography (IC) method for pharmaceuticals is the solubility of the API in water. Many drugs and intermediates are insoluble in water and other aqueous solutions that are typically used in IC systems. This poses a challenge as it could lead to precipitation of the API in the chromatography system, causing column contamination and excessive backpressure.
One solution to this dilemma is to combine sample preconcentration with matrix elimination to remove the water-insoluble API and organic solvent from the sample. This can be accomplished by replacing the system’s sample loop with a concentrator cartridge. Be sure that the direction of sample loading is opposite to that of the analytical flow.
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As an example, a pharmaceutical is dissolved in 100% MeOH and then concentrated on the concentrator cartridge, followed by elimination of the MeOH and API with deionized water. This allows determination of the target inorganic anions without interference. If you are using our Thermo Scientific Chromeleon Chromatography Data System (CDS) software, you can quickly use its program setup wizard to facilitate the concentrate and matrix elimination steps.
This approach eliminates the need for an organic solvent in the eluent or the off-line precipitation of the API, providing analytical chemists a simpler approach to determine trace anions in water-insoluble samples. Additional information including the linearity, detection limits, precision, and accuracy of this method can be found in Application Note 220, Determination of Inorganic Anion Impurities in a Water-Insoluble Pharmaceutical by Ion Chromatography with Suppressed Conductivity Detection (downloadable PDF).
Further Reading Suggestions on Our Pharma Solutions
- Drug discovery analytical applications for drug design, drug metabolism and pharmacokinetics (DMPK) lab, natural products, and metabolomics.
- Drug development analytical solutions for pre-clinical drug development; clinical trials for drug development; chemistry, manufacturing, and control for drug development; and regulatory compliance for pharmaceuticals.
- Drug manufacturing analytical solutions for QA/QC, process analytics, and regulatory compliance.
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