Posta a punt d'un procediment per la determinació de nitrit en presència d'elevades concentracions de clorur en mostres relacionades amb l'entorn farmacèutic per mètodes espectrofotomètrics i cromatogràfics


Rojas Serra, Oriol


In 2018, the Food and Drug Administration (FDA) detected trace amounts of N - dimethylnitrosamine (NDMA), a possible human carcinogen, in a wide range of drugs. The FDA, with the collaboration of several regulatory administrations, has set a maximum daily intake of nitrosamines of 0.096 mg/day.
NDMA was known to be an environmental pollutant found in drinking water, foods such as bacon, cheese or beer and its precursors had been studied to be dimethylamine (DMA) and nitrite. Under acidic conditions, dimethylamine (DMA) reacts with nitrite to form NDMA. Under these conditions, nitrite salts form nitrous acid, which can react with amine to form nitrosamine. In general, processes that use nitrite, or raw materials contaminated with nitrite, in the presence of amines present a high risk of producing nitrosamines.
This work focuses on the determination of nitrite to ensure that raw materials or drugs do not contain this precursor. Visible absorption spectrophotometry is usually used to analyze nitrite, after obtaining a derivative with the Griess reagent and ion chromatography with a conductometric detector. This work proposes the use of reverse phase chromatography with a UV-Vis detector for the determination of the Griess derivative and the use of the UV-Vis detector coupled to the exchange column, as an alternative to the conductometric detector.
Drugs can have high levels of inorganic salts such as sodium chloride, or the active ingredients can be in the form of hydrochloride. In the present work, a matrix as simple as sodium chloride is chosen as simulating the drugs. An adequate chromatographic method for the determination of the Griess derivative of nitrite has not been achieved since high chloride concentrations significantly influence the retention of this derivative. In contrast, the replacement of the conductometric detector with a UV-Vis detector has resolved the interference of high concentrations of chloride in the determination of nitrite by ion exchange chromatography. The procedure developed is selective, linear, exact and repetitive in the nitrite concentration range of 0,05 to 1,00 mg/L in the presence of high chloride concentrations. This technique allows the detection of 0,05 mg/L of nitrite in the presence of 10000 mg/L of chloride, this is equivalent to 3 mg/kg in sodium chloride.



Margarit Roig, Lourdes
Broto Puig, Francesc


IQS SE - Undergraduate Program in Chemistry