High standards have to be met by the pharmaceutical industry when it comes to drug quality and safety. These standards are documented in pharmacopoeias as officially recognized pharmaceutical rules, and published as legal tools of customer protection by authorities such as governments and medical societies. The identification of a drug depends on sensitive, reliable instruments and methods — as does the determination of the drug's compliance with applicable regulations.
Ion chromatography (IC) is the method of choice to determine active ingredients, excipients, and traces of impurities, as well as metabolites in the form of organic and inorganic ions or polar substances, in a number of pharmaceuticals, pharmaceutical solutions, and even body fluids. It can determine several substances within a very short time in a single analysis — and can even distinguish chemically similar analytes. The concentration of analytes can vary from ng/L up to the per cent range. The large selection of separation columns and elution systems available makes IC useful for almost any kind of analyte. Interfering effects caused by the sample matrix can easily be avoided by using the right sample preparation or choosing a suitable detection method. In-line sample preparation is a feature of many modern IC systems, as the focus of recent advances in IC has been mainly on ease of use. However, convenience is not the only advantage brought by automation of the IC process: Reducing human interference to a minimum also means reducing the chances of mistakes and contamination.
Depending on the requirements of analyte and matrix, there is a broad range of detection methods to choose from:
The term "pharmaceutical solutions" denotes isotonic solutions, hemodialysis solutions, or infusion solutions. They contain anions, cations, carbohydrates, and organic acids, the concentrations of which frequently differ from one another by several orders of magnitude. Within the context of production monitoring and final quality control, an analysis method is required that can determine these ingredients with a high degree of precision. In addition, the analysis should be quick and require minimal effort. With its intelligent analytical procedure and automatic in-line sample preparation, IC fully accomplishes this task.
Figure 1 shows the simultaneous determination of citrate and acetate in diluted hemodialysis solution. In part A, an anion standard was measured; part B shows the sample determination. Citrate is added to hemodialysis solutions for its anticoagulant properties and acetate is added as a buffer substance. It is transferred to the patient's bloodstream during hemodialysis and stabilizes the blood's pH value. This is necessary because the kidneys of dialysis patients are not capable of excreting acid components – therefore, patients are often acidotic.
Besides citrate and acetate, the chromatogram reveals the presence of a close to physiological concentration of chloride. By using physiological solute concentrations, the concentration gradient is reduced to a minimum and a dynamic equilibrium is reached between the blood and dialysis solution. The loss of certain solutes — including chloride — is thereby prevented.