Determination of Nitrite in Pharmaceuticals

 

N-nitrosodimethylamine (NDMA) is an organic compound with the formula (CH3)NNO. NDMA is a known carcinogen that is present in some fermented foods. Since July 2018, a few drug products including losartan, ranitidine, and metformin have been recalled by the United States Food and Drug Administration (USFDA) due to the presence of NDMA. 

Therefore, the FDA has provided industry guidance for controlling NDMA in human drugs. This has increased interest in understanding the potential of NDMA formation during pharmaceutical manufacturing. So it is important to limit the nitrite and amine levels in drug substances and drug products. 

While there are wet chemical methods for determining nitrite, ion chromatography (IC) is the typical method. IC involves separation with an ion-exchange column and conductivity, electrochemical, UV absorption, or mass spectrometry detection.

An ion chromatography method used to determine an amine in pharmaceutical samples. For nitrite, the separation is achieved by anion-exchange chromatography and detection by UV absorbance at 210 nm.

The determination of common anions, including nitrite and nitrate, is usually achieved by coupling an anion-exchange separation with suppressed conductivity detection (CD). In hydrochloride drug products, chloride is the counter ion and present at a very high concentration. The integration of a small nitrite peak in the presence of a large chloride peak can be challenging when the detection is suppressed conductivity.

The determination of LOD was based on the signal to noise (S/N) ratio. Determination of the S/N ratio is performed by comparing measured signal from a standard with a low concentration of analyte with those of blank and establishing the minimum concentration at which the analyte can be reliably detected. For method accuracy evaluation spike recovery studies to be considered.

Source: Thermo Fisher Scientific