Applications

High-Performance Liquid Chromatography (HPLC) and Ion Chromatography (IC) are commonly used in the pharma, food, and environmental sectors to analyze samples for specific components and to verify compliance with norms and standards. However, users of HPLC may run into the limitations of this technique, e.g., when analyzing standard anions or certain pharmaceutical impurities. This white paper outlines how such challenges can be overcome with IC.

Norms and Standards 21 CFR Part 11 is the FDA rule relating to the use of electronic records and electronic signatures.Recognizing the increasing impact of electronic media on critical data in regulated environments, the FDA met with members of the pharmaceutical industry in the early 1990s. The pharmaceutical industry and the FDA were interested in how they could accommodate paperless record systems and ensure the reliability, trustworthiness, and integrity of electronic records.

Chemometrics is a powerful tool widely used for method development in the pharmaceutical industry. This whitepaper describes the lifecycle of multivariate models and summarizes the workflow of the development of chemometrical models according to the new USP chapter <1039>.

This white paper summarizes the steps involved in converting an existing manual titration procedure to semi-automated or automated titration procedures. It discusses topics such as selecting the right electrode and titration mode. For a better understanding, the discussion topics are illustrated with three examples.

The objective of validation of an analytical procedure is to demonstrate that it is suitable for its intended purpose. Recommendations for the validation of analytical methods can be found in ICH Guidance Q2(R1) Validation of Analytical Procedures: Text and Methodology and in USP General Chapter <1225> Validation of Compendial Procedures. The goal of this white paper is to provide some recommendations for the validation of titration methods.

Haemophilus influenzae type B (Hib) is a major cause of bacterial meningitis in children in many countries. The capsular polysaccharide (PS) of Hib plays an important role in the virulence of the organism. The polysaccharide capsule hides cell surface components from elements of the mammalian immune system, such as antibodies and complement proteins that otherwise would activate mechanisms to kill the pathogen. Vaccines require rigorous characterization and assays to ensure final product quality and consistency. For glycoconjugate vaccines, it is important to measure both free and total PS to ensure the quality. A large amount of unconjugated PS may suppress immunity to the antigen. Additionally, the presence of free PS is a key indicator of process consistency. Current methods to determine PS content in vaccines such as Hib are imprecise and unreliable, especially if the vaccine contains a sugar stabilizer (e.g. lactose). Ion chromatography with pulsed amperometric detection (IC-PAD, or HPAEC-PAD) offers a simpler procedure and better sensitivity than other assays to quantify PS (here, polyribosylribitol phosphate [PRP]) in Hib vaccine.

By means of azide analysis in Irbesartan a simple, fast, precise and accurate ion chromatographic method for the determination of traces of inorganic contaminants in pharmaceuticals is described. Traces of toxic azides in pharmaceutical products can accurately be determined in the sub-ppb range after Metrohm Inline Matrix Elimination using isocratic ion chromatography (IC) with suppressed conductivity detection. While the azide anions are retained on the preconcentration column, the interfering pharmaceutical matrix is washed away by a transfer solution, ideally consisting of 70% methanol and 30% ultrapure water. The analytical setup provides a well-resolved azide peak and thus alleviates the common drawback of excipient interferences, especially from the nitrate anion. Calibration with azide standards is linear over the range of 5…80 ppb, providing a coefficient of determination of 0.9995. The limit of detection (LOD) and the limit of quantification (LOQ) of azide in Irbesartan are 5 and 30 µg/L respectively; the relative standard deviations (RSD) for the peak area, peak height and retention time being smaller than 3.9%. Robustness testing involved variation of column oven temperature and composition of the transfer solution and, in terms of peak area, provided RSDs smaller than 2.8% and 3.1% respectively.

The water content of tablets determines the release of their active ingredients as well as their chemical, physical, microbial and shelf-life properties. Accordingly, the water content is of crucial importance and has to be accurately determined. This paper describes the straightforward determination of the water content using automated volumetric Karl Fischer titration (KFT). Tedious sample preparation steps are eliminated by using a high-frequency homogenizer that additionally serves as a stirrer. Prior to titration, the homogenizer comminutes the tablets directly in the KF solution. As the comminution process takes place directly in the hermetically sealed titration vessels, interference from atmospheric humidity does not occur. Even after 24 h in the vessels, the moisture content of four different tablet type samples was within 93…108% of the initially determined values. With a coefficient of determination of 0.99993 the KF method is highly linear for water amounts between 4 and 215 mg. For all investigated tablet types, KFT provides results that lie within the range expected by the manufacturer.

Analytical methods to perform CU testing should ideally be fast, noninvasive and achieved with limited sample preparation. Recently, transmission near-infrared (NIR) spectroscopy and transmission Raman spectroscopy have both been explored as alternative methods for rapid and non-destructive on- and at-line CU testing with no sample preparation. Although quick and nondestructive, transmission NIR spectroscopy suffers from poor chemical selectivity and is sensitive to changes in the testing environment. Transmission Raman spectroscopy combined with chemometric modeling is quickly emerging as a valued technique for CU testing due to its high chemical specificity, which is particularly useful when dealing with complex pharmaceutical formulations that contain multiple components.

The raw materials whey, sorbitol, stearic acid, and calcium phosphate dihydrate dibasic all show very distinctive, unique Raman signatures, which indicates that Raman spectroscopy is the ideal technology for identification of these materials. The PCA model-based method provides reliable specificity to successfully identify these nondestructively in plastc samples bags using the NanoRam.