Applications for GCMS

 

Thermal Desorption – GCMS Method for Screening Analysis of Extractables in Drug Packing Materials

Both extractables and leachables (E&L) from pharmaceutical packaging materials and products are of utmost concerns by authorities, since they may affect the efficacy, quality and safety. Many regulatory guidance documents have been established regarding E&L approach and assessment. However, details on how to perform E&L evaluation in various packaging materials and products are still under discussion and development. Extractables are defined as the compounds that can be extracted from a drug packaging under certain conditions, e.g. in solvent and/or with heating. Leachables are compounds that migrate from the drug packaging into the drug under normal storage condition. Theoretically, leachables emerge from extractables, although not all leachables are extractable in practice. Special analysis methods are needed for the detection and quantitation of extractables and leachables on pharmaceutical packaging and products.

 
 
 
 
 
 

Analysis of N-Nitrosodimethylamine (NDMA) & N-Nitrosodiethylamine (NDEA) in pharmaceutical substance by HSGCMS

N-Nitrosodimethylamine (NDMA) & NNitrosodiethylamine (NDEA) are simplest of Dialkylnitrosamines. They are continued to be released as a by-product and contaminant from various industries and from municipal wastewater treatment plants. Major releases of NDMA, NDEA have been from the manufacture of pesticides, rubber tires, alkyl amines, and dyes. Similarly, these compounds are produced as a byproduct in the manufacturing of Active Pharmaceutical Ingredients (API’s). These compounds are classified as a Group 2A carcinogen (probable human carcinogen) by the World Health Organization.

 
 
 
 
 
 

Quantitation of 7 Nitrosamines in API by HSGC-MSMS as per proposed USP General Chapter

Nitrosamines refer to any molecule containing the nitroso functional group. Although they are also present in some foods and drinking water supplies, their presence in drugs is considered unacceptable. NDMA and NDEA belong to the so-called “cohort of concern”, which is a group of highly potent mutagenic carcinogens that have been classified as probably human carcinogens (PGI). The Drug Regulatory Authorities first noticed the presence of the nitrosamine impurity (NSA), N[1]Nitrosodimethylamine (NDMA) in products containing valsartan in July 2018. Valsartan is an Angiotensin II Receptor Blocker (ARB) and belongs to a family of analogue compounds commonly referred to as the Sartans.

 
 
 
 
 
 

Analysis of Potential Genotoxic Impurities in Active Pharmaceutical Ingredients

Chemicals such as methanesulfonic acid (mesylate), benzenesulfonic acid (besilate), and p-toluenesulfonic acid (tosylate) are used in the process of synthesizing active pharmaceutical ingredients. These compounds are likely to generate sulfonic acid ester as a reaction byproduct. These compounds are known as potential genotoxic impurities (PGI) and are a significant cause for concern among pharmaceutical manufacturers. This article introduces the analysis of sulfonic acid esters utilizing the GCMS-QP2010 Ultra.

 
 
 
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