Aplikace

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.

Pharmaceutical analysis guarantees drug safety by providing information on the identity, content, quality, purity, and stability of pharmaceutical products using analytical chemistry. Ion chromatography (IC) offers a broad range of pharmacopeia-compliant applications for quality control, monitoring, and improving drug manufacturing.As a very accurate and versatile technique, IC meets the requirements of many pharmaceutical applications. IC is a USP-accepted standard method for the determination of active pharmaceutical ingredients (APIs), excipients, impurities,pharmaceutical solutions as well as pharmaceutical starting materials, finished pharmaceutical products (FPPs) and even body fluids.This poster describes some typical examples.

This poster presented jointly with USP at AAPS meeting shows, that we successfully validated an IC method to determine chloride and sulfate in drug substances, potassium bicarbonate and potassium carbonate. The proposed IC method overcomes limitations of the turbidimetry/visual comparison methods.

Determination of tributylamine in a pharmaceutical product (gabapentine) using cation chromatography with direct conductivity detection.

Determination of N-methylpyrrolidone (N-MP) in a pharmaceutical product (Cefepime Hydrochloride) using cation chromatography with direct conductivity detection.

Determination of Bethanechol chloride and calcium in tablets using cation chromatography with direct conductivity detection.

Determination of Bethanechol Chloride and HPTA (2-hydroxy-propyl-trimethyl ammonium chloride) besides sodium and calcium using cation chromatography with direct conductivity detection.

Bethanechol is a pharmaceutical compound which is used to treat urinary retention. This API (active pharmaceutical ingredient) can be determined by cation chromatography with direct conductivity detection. A good separation is achieved between bethanechol and its degradation product 2-hydroxy-propyl-trimethyl ammonium (HPTA) and the standard cations. Peak shape and resolution meet the USP requirements for bethanechol.

Potassium bitartrate for pharmaceutical use must comply with USP requirements. The actual monograph (USP 42) uses a colorimetric method for the determination of ammonium impurities. Ion chromatography allows the measurement in a single determination under the same conditions used for the potassium assay (see AN-C-181). In the course of the USP monograph modernization, this ion chromatographic approach makes this type of analysis even easier.

Atorvastatin is a medication that is used for reducing cholesterol levels. A sensitive and reliable method for TBA detection is required, given that trace amounts of tetrabutylammonium (TBA) are to be found in the presence of atorvastatin and its derivatives. One such method is ion chromatographic separation on the Metrosep C Supp 1 - 250/4.0 with subsequent conductivity detection and sequential suppression.

Meropenem is a beta-lactam antibiotic that is classed among the carbapenems; it suppresses murein biosynthesis and thus the buildup of the bacterial cell wall. Dimethylamine is an important precursor in meropenem synthesis and must therefore be monitored as an impurity. Detection is performed on the Metrosep C Supp 1 - 250/4 column with subsequent conductivity detection after sequential suppression.

Succinylcholine is a short-term paralyzing agent used e.g., for tracheal intubation. Choline is a building block of the drug and needs to be determined as an impurity. USP applies cation chromatography with conductivity detection after suppression. Eluent composition and column type do not exactly comply with the USP method. However, the results fulfill the respective requirements. The choline concentration of the sample is out of USP specifications.

Determination of chloride in bethanechol tablets using anion chromatography with conductivity detection after chemical suppression.

Topiramate is an antiepilepsy drug. According to USP Topiramate tablets have to be tested for impurities. The determination of sulfate and sulfamate is mentioned under 'Specific Tests'. The isocratic method applies a column eluent combination primarily used for non-suppressed IC. But as sulfamate shows a negative peak under theses conditions the use of suppression is advantageous.

Pamidronate is applied to treat osteoporosis by strengthening the bones. It is a bisphosphonate containing a primary amine group. Phosphite and phosphate are related compounds, which need to be quantified. USP requires the use of formic acid eluent with refractive index detection. But a standard IC procedure offers an alternative with better sensitivity. Phosphite and phosphate are analyzed with conductivity detection after sequential suppression.

As an alternative to titration, ion chromatography (IC) with suppressed conductivity detection has been approved by USP as validated method to quantify chloride content in NaCl tablets for solution or oral use.

Determination of salicylic acid and acetylsalicylic acid according to USP 28-NF 23 (second supplement) using RP chromatography with UV detection.

The pharmaceutical industry is very likely more comprehensively regulated that any other branch of industry. It therefore requires analytic methods that meet the requirements of regulations while at the same time being practical. This applies in particular for large sample quantities, such as are encountered with incoming goods inspections, for example. It is here that particularly rapid and simple analysis methods are called for which make routine analyses simpler and more efficient. This White Paper describes some of the most important regulations in the pharmaceutical analysis and shows how Vis-NIR spectroscopy can solve analytic problems in the pharmaceutical industry in accordance with regulations.

Ion chromatography is a flexible technique with a large selection of intended uses in the pharmaceutical industry. – A few development trends and the latest advances are displayed here.

Underestimation of quality control (QC) processes is one of the major factors leading to internal and external product failure, which have been reported to cause a loss of turnover between 10–30%. As a result, many different norms are put in place to support manufacturers with their QC process. However, time to result and the associated costs for chemicals can be quite excessive, leading many companies to implement near-infrared spectroscopy (NIRS) in their QC process. This paper illustrates the potential of NIRS and displays cost saving potentials up to 90%.

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.