Related Experiment Video
Updated: Mar 29, 2026
08:25
Measuring Nitrite and Nitrate, Metabolites in the Nitric Oxide Pathway, in Biological Materials using the Chemiluminescence Method
Published on: December 25, 2016
23.2K
Analysis of nitrite in pharmaceutical excipients: A multi‑laboratory comparative study
Giorgio Blom1, Tamas Balogh2, Petra Loos3
1Chemical Development, Pharmaceutical Technology and Development, Operations, AstraZeneca, Macclesfield, UK.
Summary
Controlling nitrosamine impurities in drugs requires understanding nitrite levels in excipients. A comparative study highlighted variability in nitrite analysis, especially for magnesium stearate, emphasizing the need for rigorous method validation.
Area of Science:
- Pharmaceutical analysis
- Impurity profiling
- Chemical risk assessment
Background:
- N-nitrosamine impurities in pharmaceuticals pose carcinogenicity risks.
- Nitrosamine formation is linked to amine and nitrite reactions, with nitrite often being the limiting factor.
- Accurate quantification of nitrite in excipients is crucial for assessing nitrosamine formation potential.
Purpose of the Study:
- To evaluate the accuracy and variability of nitrite quantification in common pharmaceutical excipients.
- To compare different analytical methods for trace nitrite detection in excipients.
- To inform updated guidance for method validation within the pharmaceutical industry.
Main Methods:
- A comparative testing study involving six independent laboratories.
- Analysis of microcrystalline cellulose, magnesium stearate, and lactose using ion chromatography (IC-CD), Griess/LC-UV, and DAN/LC-FLR.
- Evaluation of results based on detection method, extraction, and clarification procedures.
Main Results:
- Consistent nitrite results were observed for lactose across laboratories.
- Matrix interference prevented quantifiable nitrite detection in microcrystalline cellulose.
- Significant variability in magnesium stearate analysis was linked to sonication in sample preparation.
Conclusions:
- Trace level nitrite analysis in excipients exhibits potential variability.
- Method characterization, including specificity, accuracy, and precision, is essential.
- Updated guidance for method validation has been disseminated by the Lhasa Nitrites consortium.
Related Concept Videos
01:202° Amines to N-Nitrosamines: Reaction with NaNO2
5.7K
Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
5.7K
01:19Pharmaceutical Alternatives: Excipients and Impurities-Related Therapeutic Nonequivalence
224
Pharmaceutical products contain more than just the active drug; they also contain various excipients such as binders, solubilizers, stabilizers, preservatives, and other elements. In some cases, impurities or contaminants might be present. Traditionally, quality control in pharmaceuticals has primarily focused on the analysis of the active drug, often overlooking the impact of these additional components. The recent issue with heparin contamination by over-sulfated chondroitin sulfate, a...
224
01:28Factors Influencing Drug Absorption: Pharmaceutical Parameters
760
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
760
01:261° Amines to Diazonium or Aryldiazonium Salts: Diazotization with NaNO2 Overview
4.0K
Nitrous acid and nitric acids are two types of acids containing nitrogen, among which nitrous acid is weaker than nitric acid. Nitrous acid with a pKa value of 3.37 ionizes in water to give a nitrite ion and the hydronium ion.
The nitrous acid is unstable. Hence, it is formed in situ from a solution of sodium nitrite and cold aqueous acids such as hydrochloric or sulfuric acid. In an acidic solution, the –OH group of nitrous acid undergoes protonation to give oxonium ion, followed by...
The nitrous acid is unstable. Hence, it is formed in situ from a solution of sodium nitrite and cold aqueous acids such as hydrochloric or sulfuric acid. In an acidic solution, the –OH group of nitrous acid undergoes protonation to give oxonium ion, followed by...
4.0K
01:29Preparation of Amines: Reduction of Oximes and Nitro Compounds
4.9K
Oximes can be reduced to primary amines using catalytic hydrogenation, hydride reduction, or sodium metal reduction. The reduction of aliphatic and aromatic nitro compounds to primary amines takes place by either catalytic hydrogenation or by using active metals like Fe, Zn, and Sn in the presence of an acid.
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
4.9K
01:22Inorganic Nitrogen Assimilation
799
Nitrogen is an essential element in biological systems, forming a crucial component of proteins, nucleic acids, and other cellular constituents. Many bacteria and archaea acquire nitrogen in the form of nitrate (NO₃⁻) or ammonia (NH₃), which are then assimilated into biomolecules through specific enzymatic pathways.Assimilatory Nitrate ReductionWhen nitrate enters the cell, it undergoes a two-step reduction process known as assimilatory nitrate reduction. Initially, the enzyme...
799