What is the role of Meglumine in Pharma?
To understand the N-Nitroso Meglumine and its significance, we must first discuss its precursor, Meglumine. Methylglucamine, or Meglumine, is widely used as an excipient in the pharma industry. It is used to improve the solubility and stability of poorly soluble drugs for better absorption of the drug molecules in the body. Due to its ability to buffer formulations and create salt forms of APIs, it is an invaluable compound in formulating oral and injectable dosage forms. It is also a popular contrast agent used in diagnostic imaging. During the manufacturing processes or storage steps, the formation of N-Nitroso meglumine can occur due to the contamination by nitrosating agents.
What is N-Nitroso Meglumine?
N-Nitroso Meglumine belongs to the class of N-Nitrosamine impurities, known for their potential carcinogenicity. These impurities form under specific chemical conditions, in the presence of nitrites and secondary or tertiary amines under acidic conditions. Below is the structure of Meglumine.
As its structure reveals, Meglumine is a nitrogen-containing compound that can be nitrosated during its manufacturing and storage. There is a high chance of the formation of N-Nitroso Meglumine if a nitrosating agent like sodium nitrite is present in raw materials or even in the processing environment. When a nitrosated byproduct is present even in trace amounts, it can pose a serious health risk if left unchecked.
Other Details of N-Nitroso Meglumine:
1) Chemical Name: N-Methyl-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)nitrous amide; 1-Deoxy-1-(methylnitrosamino)-D-glucitol
2) Product Code: 87309
3) CAS number: 10356-92-0
4) Molecular Weight: 224.21 g/mol
5) Mol. formula: C7H16N2O6
The Structure of N-Nitroso Meglumine is:
Why check Nitrosamine Impurities?
Recently, regulatory agencies like the US FDA, EMA, and ICH have tightened their scrutiny over the presence of nitrosamine impurities in pharma products. The Nitrosamine impurities, including N-Nitrosodimethylamine and N-Nitrosodiethylamine (NDEA), were the first impurities detected in widely consumed medicines such as sartan-based antihypertensives and metformin.
Since then, the regulatory framework has evolved rapidly. The ICH M7 and ICH Q3A/Q3B guidelines now emphasize the significance of not just identifying, but quantifying, and controlling the potentially genotoxic impurities like N-Nitrosamines.
Therefore, manufacturers must validate the analytical methods employed to detect and quantify this impurity at ppt and ppb levels. In case of failure to do so, it can result in serious consequences such as non-compliance, product recalls and restrictions in key markets.
Detect and Quantify N-Nitroso Meglumine
Since it is carcinogenic, it is crucial to detect it with 100% accuracy. Accurate detection and quantification are non-negotiable during the development of analytical methods, validation protocols, stability studies, and product testing when produced on a commercial scale.
Highly sensitive techniques such as Liquid Chromatography, GC-MS, or HPLC with UV or fluorescence detection are employed to identify and quantify nitrosamines. While developing a specific detection method, one must ensure the LOD (Limit of Detection) and LOQ (Limit of Quantification) remain within the acceptable intake limits per the regulations. The acceptable intake limit is usually in the range of 18ng/day and lower for numerous nitrosamines.
To develop methods and for calibrations, you need highly pure reference standards. Advent offers such fine and specialty chemicals in highly pure form!
Where to Buy N-Nitroso Meglumine?
At Advent, we have successfully developed N-nitroso meglumine on a milligram to gram scale, with a more than 95% purity. This impurity standard can be used as a working standard in validated testing procedures, supporting both R&D and quality control in pharma companies.
In addition to the chemical, we also provide you with its comprehensive characterization, which includes:
1) 1H NMR: to confirm the proton environment and structural integrity of the compound
2) Mass Spectrometry: to verify the molecular weight and its identity
3) Infrared Spectroscopy: to confirm the functional groups
4) Thermogravimetric Analysis: to assess its stability and moisture content
With this data, you can confidently use N-Nitroso Meglumine standards in your analytical workflows for accuracy, traceability, and regulatory compliance. These working standards are available to companies in India and abroad for better risk assessment of the nitrosamine impurities and better control.
Applications of N-Nitroso Meglumine
Every time you use meglumine in your pharmaceutical formulation, there is a high chance that this impurity will be present and, therefore, must be monitored. These are the critical areas where this impurity standard is a necessity:
1) Manufacturing of contrasting agents like iopamidol and iomeprol.
2) Production of injectable formulations having meglumine salts.
3) Processing of drug substances or intermediates with meglumine as a solubilizing agent.
4) To analyze meglumine-based formulations in the R&D lab.
Benefits of using impurity standards in Pharma
When pharma companies develop new complex formulations, the presence of impurities with carcinogenic potential can prove to be a threat to patient safety. As it is rightly said, “Prevention is better than cure,” it is always better to strictly check the impurities even in trace levels to avoid non-compliance with the regulatory standards.
The Impurity standards help Pharma Companies in ways like:
Ensures Regulatory Readiness: Without any worries, you can be ready for an audit when using the impurity standards to validate your methods.
Preventing Product Recalls: As you validate and strictly control the quality of your products, there are fewer chances of facing situations like product recalls. It is highly cost-effective.
Improving Patient Safety: When you use impurity standards, you do not need to worry about patient safety and product withdrawal after being distributed in the market.
Reinforcing Brand Credibility: Just like “Rome was not built in a day”, building the brand trust in the market takes years of effort. This brand trust could be easily lost if the FDA recalls the product.
Find your Eureka Moment!
Advent offers fine and specialty chemicals for your every reaction and every process. With more than 3000 products in the basket, we offer you the best in the market of impurity standards. To find your Eureka moment, visit our website today!
