A Full Evaporation Static Headspace Gas Chromatography Method with Nitrogen Phosphorous Detection for Ultrasensitive Analysis of Semi-volatile Nitrosamines in Pharmaceutical Products

The recent detection of potent carcinogenic nitrosamine impurities in several human medicines has triggered product recalls and interrupted the supply of critical medications for hundreds of millions of patients, illuminating the need for increased testing of nitrosamines in pharmaceutical products. However, the development of analytical methods for nitrosamine detection is challenging due to high sensitivity requirements, complex matrices, and the large number and variety of samples requiring testing. Herein, we report an analytical method for the analysis of a common nitrosamine, N-nitrosodimethylamine (NDMA), in pharmaceutical products using full evaporation static headspace gas chromatography with nitrogen phosphorous detection (FE-SHSGC-NPD). This method is sensitive, specific, accurate, and precise and has the potential to serve as a universal method for testing all semi-volatile nitrosamines across different drug products. Through elimination of the detrimental headspace-liquid partition, a quantitation limit of 0.25 ppb is achieved for NDMA, a significant improvement upon traditional LC-MS methods. The extraction of nitrosamines directly from solid sample not only simplifies the sample preparation procedure but also enables the method to be used for different products as is or with minor modifications, as demonstrated by the analysis of NDMA in 10+ pharmaceutical products. The in situ nitrosation that is commonly observed in GC methods for nitrosamine analysis was completely inhibited by the addition of a small volume solvent containing pyrogallol, phosphoric acid, and isopropanol. Employing simple procedures and low-cost instrumentation, this method can be implemented in any analytical laboratory for routine nitrosamine analysis, ensuring patient safety and uninterrupted supply of critical medications.

New Insights into the Chemical Reactivity of Dry-Cured Fermented Sausages: Focus on Nitrosation, Nitrosylation and Oxidation

Nitrite and nitrate are added to cured meat for their bacteriological, technological and sensorial properties. However, they are suspected to be involved in the formation of nitroso compounds (NOCs), such as potentially mutagenic nitrosamines, nitrosylheme and nitrosothiols. Controlling the sanitary and sensorial qualities of cured meat products by reducing these additives requires elucidating the mechanisms involved in the formation of NOCs. To this end, we studied the dose-response relationship of added sodium nitrite and/or sodium nitrate (0/0, 80/80, 0/200, and 120/120 ppm) on the formation of NOCs in dry cured fermented sausages. The results showed a basal heme iron nitrosylation in the absence of NaNO2/NaNO3 due to starter cultures. This reaction was promoted by the addition of NaNO2/NaNO3 in the other conditions. Reducing the dose to 80/80 ppm still limits lipid oxidation without the formation of non-volatile nitrosamines. Conversely, the addition of NO2/NO3 slightly increases protein oxidation through higher carbonyl content. The use of 80/80 ppm could be a means of reducing these additives in dry-cured fermented meat products.

Polymorphisms of CYP2E1 rs2031920 is not Associated with Risk of Nasopharyngeal Carcinoma in Minangkabau Ethnic Group

BACKGROUND: Various environmental factors have been suspected to be associated with the risk of developing Nasopharyngeal Carcinoma (NPC). Volatile nitrosamines found in salted fish are thought to be carcinogenic substances for NPC. Nitrosamines are activated by the CYP2E1 enzyme. Several studies investigated the relationship between polymorphism in the CYP2E1 gene and susceptibility to NPC, but the results obtained were inconsistent. AIM: This study was conducted to analyse the association of the CYP2E1 rs2031920 polymorphisms with the incidence of NPC in the Minangkabau ethnic group. METHODS: The subjects of this study were newly diagnosed NPC Minangkabau ethnic patients, while the controls were healthy people. A total of 23 cases of NPC and 23 aged (± 3 years) and sex-matched controls participated in the study. The method used to identify these polymorphisms is PCR sequencing. RESULTS: On recent study, we found CYP2E1 rs2031920 gene polymorphism in both the NPC and control groups, in the NPC group there were 8.7% heterozygote mutants while in the control group there were 26.1% heterozygote mutants, and there were no homozygote mutants in the two groups, and statistically none a significant relationship between CYP2E1 gene polymorphism and the incidence of NPC, with p > 0.05. CONCLUSION: Our study reveals that there is no association of CYP2E1 gene polymorphism (rs2031920) with the incidence of nasopharyngeal carcinoma in the Minangkabau ethnic group.