Drug characterization and quantitation, and purity, counterion, and excipient analyses
Most pharmaceuticals are produced synthetically in bulk then formulated into small dosage forms such as tablets or injectables. Many of these substances are manufactured in specific salt forms to promote solubility, stability, and bioavailability. The most common pharmaceutical counterions used in the development of basic drugs are chloride and sulfate.
Analysis of pharmaceuticals
It is important to accurately determine the concentration of these counterions to establish the correct molecular mass of the drug, the stoichiometric relationship between the drug and counterion, and the completeness of salt formation. During the early stages of drug product development, it is also critical to determine the concentrations of unknown ionic impurities.
Ion chromatography can simultaneously determine multiple cations in a single injection. Suppressors significantly reduce background conductivity and increase the analyte signal, thereby providing very low detection limits. Using a Thermo Scientific™ Reagent-Free™ Ion Chromatography (RFIC™) system with electrolytically generated eluent simplifies the method and enhances method reproducibility between laboratories.
Regulatory information
- ICH, International Conference on Harmonization: established guidelines for the control of impurities in pharmaceuticals propose a qualification threshold of 0.1% if the maximum daily dose is ≤2g/day and 0.05% if the maximum daily dose exceeds 2g/day.
- MHRA, Medicines and Healthcare Regulatory Agency: In the UK, all new medicines have to be assessed and authorized by the MHRA before they can be sold. The MHRA also operates a Yellow Card system for reporting, investigating and monitoring suspected side effects or adverse reactions to medicines.
- WHO: Develops and maintains global norms, international standards and guidelines for the quality, safety and efficacy of drugs.
- FDA: Center for Drug Evaluation and Research (CDER) evaluates new drugs before they hit the market, ensuring that brand-name and generic drugs work correctly and that their health benefits outweigh their known risks.
Example application notes
| Application Notes | Analyte/Sample Type | MDL | IC Columns |
|---|---|---|---|
| Determination of Bethanechol by Ion Chromatography (AN 148) | Bethanechol | 0.05mg/L | Dionex IonPac CS1 Columns |
| Assay of Nitrite and Determination of Nitrate Impurity in Sodium Nitrite Using a Reagent-Free IC (AN 1148) | Sodium nitrite | 43.6–97.3mg/L | Dionex IonPac AS12A Columns |
| IC Assay for Lithium, Sodium, and Calcium in Lithium Carbonate (AN 1090) | Lithium carbonate | 0.27–7.4mg/L | Dionex IonPac CS16 Columns |
| Sulfate Counter Ion and Anionic Impurities in Aminoglycoside Drug Substances by IC with Suppressed Conductivity Detection (AN 190) | Aminoglycoside sulfate compounds | 3.0–9.3mg/L | Dionex IonPac AS18 Columns |
| HPAE-PAD Determination of Cyclodextrins (AN 73011) | Sulfobutyl Ether Sodium monograph | Dionex CarboPac PA200 |
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