Nitrosamine Compounds Research Articles

Protective Effect of Fish Oil and Virgin Olive Oil on Diethylnitrosamine Toxicity in Rats

Liver injury induced by viruses, toxic chemicals, certain drugs and environmental pollutants, has been on the increase for the past few decades and recognized as a toxicological problem. Nitrosamine compounds are known hepatic carcinogens. The present study was carried out to investigate the hepatoprotective effect of fish oil and virgin olive oil against diethylnitrosamine (DEN) intoxication in rats compared with drug (25mg/kg diet). Wister rats weighing 200 ± 5 g were induced hepatotoxicity by injection of DEN (via single intraperitoneally injection at 150 mg/kg/body weight). Rats were divided into 9 groups (n = 6) of non- hepatotoxicity, non- hepatotoxicity and treated, hepatotoxicity non-treated and hepatotoxicity treated with drug, fish oil, virgin olive oil. After 8 weeks the rats feeding with fish oil, virgin olive oil supplied to hepatotoxicity rats instead of diet significant improvement in lipid profile and liver function. However, a significantly increment in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSPx) and glutathione reduced (GSH) were observed in blood of hepatotoxicity rats treated with fish oil, virgin olive oil and mixtures. The treated groups showed a significant decrement in thiobarbituric acid reactive substances (MDA) in serum. Since the study of induction of the redox enzymes is considered to be a reliable marker for evaluating the antiperoxidative efficacy of the fish oil and virgin olive oil. Treatment with fish oil and virgin olive oil reduces the histopathological liver abnormalities associated with hepatotoxicity. Moreover to the anti hepatotoxicity effect and possess antioxidant potential that may be used for therapeutic purposes suggested. The present study showed that fish oil, virgin olive oil were able to prevent or reduce the severity of diethylnitrosamine -induced liver injury.

Distribution of groundwater nitrate contamination in GIS environment: A case study, Sonqor plain

Background: Nitrate is a pollutant of groundwater resources which can results health risks such as methemoglobinemia and formation of nitrosamine compounds in higher concentration limits. The present study was aimed to determine the nitrite level, causes of pollution and zonation of nitrite concentration in drinking water resources in the villages of Sonqor. Methods: In this descriptive-analytrical study, 73 samples of all groundwater resources of Sonqor plain were taken in ,high water (March 2010) and low water (September 2011) periods. Water nitrate levels were then determined by spectrophotometry. Results were compared by national standards and analyzed by SPSS and Arcview GIS 9.3 software. Finally, the concentration distribution mapping was carried out in GIS environment and the factors affecting nitrite changes were analyzed. Results: nitrate concentration of water resources of Sonqor plain was fluctuating at 3.09-88.5 mg per liter.In one station, nitrite concentrations in the high (88.5 mg/liter) and low (71.4 mg/liter) water seasons were higher than the maximum limit. Based on the maps, a relatively high concentration of nitrite was observed in the Eastern and Southeastern regions. Conclusion: The findings indicated a reverse correlation between nitrite concentration changes and changes of static surface depth. Low thickness of alluvium, location of wells in the downstream farmlands, farming condition of the region, nitrate leaching from agricultural soils and wide application of nitrogen fertilizers in agriculture were considered as the causes of the pollution in one station.

Determination of Seven Volatile N-Nitrosamines in Fast Food

In this study, various fast food samples, including raw meat, cured meat, grilled meat, fried meat, smoked meat and canned meat products, were analyzed for the determination of the seven volatile N-nitrosamines. The samples were treated with an aqueous sodium hydroxide (NaOH) by autoclaving at 121°C for 10 min and extracted by liquid-liquid extraction with dichloromethane, and then the nitrosamines were pre-concentrated by using activated silica. Then, gas chromatography coupled with flame ionization detector was used for the separation and determination of the different nitrosamines contained in a real sample. The applied method allowed the determination of nitrosamine compounds at trace levels with limit of detection ranging from 0.077 to 0.18 ppb, and quantitation limits were from 0.26 to 0.60 ppb for all nitrosamines. The total concentrations of the seven nitrosamines in the studied meat samples ranged from 2.60 to 13.28 μg/kg.

Determination of volatile nitrosamines in urine through gas chromatography-mass spectrometry

To establish a detection method based on gas chromatography-mass spectrometry (GC-MS) for concentrations of volatile nitrosamine compounds in urine, and apply it to the test of real samples. Target compounds dichloromethane in urine samples was extracted with dichloromethane through liquid-liquid extraction, then the dichloromethane extract was filtrated, evaporated with nitrogen at 40°C to dryness, and the volume was set with 0.2 ml dichloromethane. Analysis of nine volatile nitroso-compounds were performed with GC-MS under selected ion monitoring mode, external reference method was used for quantification, and the detection limit, repeatability and sensitivity were evaluated. In addition, nine volatile nitroso-compounds of 92 urine samples in a town of Anhui province were measured. A good linear range of 2 - 200 ng/ml (with correlation coefficient 0.9985 - 0.9999) were obtained for the above mentioned nine kinds of analyte, and the lowest examination concentration was 0.05 - 0.50 ng/ml. The addition standard recoveries were 68%-102% with the RSD of 0.4% - 5.5% (n = 3). The detection limits were 0.001 - 0.013 ng/ml urine. The detection rate of N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n-propylamine (NDPA), N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR), N-nitrosopiperidine (NPIP), N-nitrosodi-n-butylamine (NDBA) and N-nitrosodiphenylamine (NDPhA) were 71% (65), 74% (68), 65% (60), 80% (73), 92% (85), 78% (72), 76% (70), 87% (80), 98% (90), respectively, with the results (0.27 ± 0.12), (0.75 ± 0.29), (0.06 ± 0.02), (0.16 ± 0.07), (23.66 ± 5.18), (1.01 ± 0.35), (0.38 ± 0.11), (2.47 ± 0.52) and (15.13 ± 3.48) nmol/g creatinine. A gas chromatography-mass spectrometry detect method was developed for low level volatile nitrosamines in urine samples.

Rapid and Simple Extraction Method for Volatile N-Nitrosamines in Meat Products

A new methodology for extraction, pre-concentration and analysis of volatile nitrosamines in meat-derived products was developed and compared with conventional methods (Distillation and two-step solid-phase extraction). The samples (canned sausages, cured meat, luncheon and smoked meat) were treated with an aqueous sodium hydroxide (NaOH) by autoclaving at 121°C for 10 min and extracted by liquid-liquid extraction with dichloromethane, then the nitrosamines were pre-concentrated using activated silica. Then, gas chromatography coupled with flame ionization detector was used for the separation and determination of the different nitrosamines contained in a real sample and gas chromatography with mass spectrometry detection was used as the confirmation technique. The newly invented autoclaving method allowed the determination of nitrosamine compounds at trace levels with limit of detection ranged from 0.077 to 0.18 ppb and quantitation limits were from 0.26 to 0.6 ppb for all nitrosamines, and found to be superior to the conventional ones, yielding approximately about 10%-20% increasing in the recovery compared with the mean recovery obtained when applying conventional methods.

Nitrosamine occurrence at Korean surface water using an analytical method based on GC/LRMS

The survey of nitrosamine occurrence at Korean surface water of Nakdong river is conducted in this study. For this purpose, the nitrosamine analytical method based on more affordable GC/LRMS (low resolution mass spectrometry) has been developed. According to the study results, six nitrosamine compounds (NDEA as N-nitrosomethylethylamine, NDPA as N-nitrosodi-n-propylamine, NDMA as N-nitrosodimethylamine, NMEA as N-nitrosomethylethylamine, NDBA as N-nitrosodi-n-butylamine, and NDPHA as N-nitrosodiphenylamine) were detected at the Nakdong river. Among these, NDEA and NDPA are the most important compounds in terms of the nitrosamine contamination of the Nakdong river. The detected concentration of NDEA exceeded the CDHCS (California Department of Health Care Services) response level of 100 ng/L at several sites. The detected concentration of NDPA approached the response level (500 ng/L) at a few sites. When all nitrosamine concentrations were summed up, the maximum concentration of 735.7 ng/L was detected at the Nakdong river. An equation describing a decrease in total nitrosamine concentration along downstream sampling sites was proposed in this study. The equation can be used to predict the downstream nitrosamine contamination at the Nakdong river. Among various water quality parameters, T-N showed a good correlation with total nitrosamine concentration.

7-Azabicyclo[2.2.1]heptane as a structural motif to block mutagenicity of nitrosamines

Nitrosamines are potent carcinogens and toxicants in the rat and potential genotoxins in humans. They are metabolically activated by hydroxylation at an α-carbon atom with respect to the nitrosoamino group, catalyzed by cytochrome P450. However, there has been little systematic investigation of the structure–mutagenic activity relationship of N-nitrosamines. Herein, we evaluated the mutagenicity of a series of 7-azabicyclo[2.2.1]heptane N-nitrosamines and related monocyclic nitrosamines by using the Ames assay. Our results show that the N-nitrosamine functionality embedded in the bicyclic 7-azabicylo[2.2.1]heptane structure lacks mutagenicity, that is, it is inert to α-hydroxylation, which is the trigger of mutagenic events. Further, the calculated α-C–H bond dissociation energies of the bicyclic nitrosamines are larger in magnitude than those of the corresponding monocyclic nitrosamines and N-nitrosodimethylamine by as much as 20–30 kcal/mol. These results are consistent with lower α-C–H bond reactivity of the bicyclic nitrosamines. Thus, the 7-azabicyclo[2.2.1]heptane structural motif may be useful for the design of nongenotoxic nitrosamine compounds with potential biological/medicinal applications.

Identification of Candida albicans by using different culture medias and its association in potentially malignant and malignant lesions

Background and Objective:The present study evaluates the association of Candida albicans with normal control group, potentially malignant and malignant lesions of oral cavity by using two different liquid culture media.Materials and Methods:Saliva was collected and biopsy was taken only from those clinically suspected potentially malignant and malignant lesions for histopathological diagnosis. Saliva samples were inoculated for fungal growth in Sabouraud's dextrose agar and culture-positive samples had undergone for Germ tube test. Germ tube-positive samples were further taken for quantification of chlamydospore production in liquid media at 8 and 16 hours.Results:In normal control groups no fungus growth was found; however, potentially malignant and malignant cases showed fungus growth, positive germ tube test and chlamydospore formation. The result also showed rapid and quantitatively more chlamydospore formation in corn meal broth + 5% milk in comparison to serum milk culture media.Conclusion:The oral mucosa is compromised in potentially malignant lesions, it can be argued that this species may be involved in carcinogenesis by elaborating the nitrosamine compounds which either act directly on oral mucosa or interact with other chemical carcinogens to activate specific proto-oncogenes and thereby initiate oral neoplasia.

CpG island hypermethylation of multiple tumor suppressor genes associated with loss of their protein expression during rat lung carcinogenesis induced by 3-methylcholanthrene and diethylnitrosamine

The epigenetic mechanisms underlying the tumorigenesis caused by polycyclic aromatic hydrocarbons and nitrosamine compounds such as 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN) are currently unknown. We reported previously that dynamic changes in DNA methylation occurred during MCA/DEN-induced rat lung carcinogenesis. Here, we used the same animal model to further study the evolution of methylation alterations in tumor suppressor genes (TSGs) DAPK1, FHIT, RASSF1A, and SOCS-3. We found that none of these genes were methylated in either normal or hyperplasia tissue. However, as the severity of the cancer progressed through squamous metaplasia and dysplasia to carcinoma in situ (CIS) and infiltrating carcinoma, so methylation became more prevalent. Particularly dramatic increases in the level of methylation, the average number of methylated genes, and the incidence of concurrent methylation in three genes were observed in CIS and infiltrating carcinoma. Similar but less profound changes were seen in squamous metaplasia and dysplasia. Furthermore, methylation status was closely correlated to loss of protein expression for these genes, with protein levels markedly declining along the continuum of carcinogenesis. These results suggest that progressive CpG island hypermethylation leading to inactivation of TSGs might be a vital molecular mechanism in the pathogenesis of MCA/DEN-induced multistep rat lung carcinogenesis.

Ameliorating effect of chicory ( Cichorium intybus L.)-supplemented diet against nitrosamine precursors-induced liver injury and oxidative stress in male rats

The current study was carried out to elucidate the modulating effect of chicory ( Cichorium intybus L.)-supplemented diet against nitrosamnine-induced oxidative stress and hepatotoxicity in male rats. Rats were divided into four groups and treated for 8 weeks as follow: group 1 served as control; group 2 fed on chicory-supplemented diet (10% w/w); group 3 received simultaneously nitrosamine precursors [sodium nitrite (0.05% in drinking water) plus chlorpromazine (1.7 mg/kg body weight)] and group 4 received nitrosamine precursors and fed on chicory-supplemented diet. The obtained results revealed that rats received nitrosamine precursors showed a significant increase in liver TBARS and total lipids, total cholesterol, bilirubin, and enzymes activity (AST, ALT, ALP and γ-GT) in both serum and liver. While a significant decrease in the levels of GSH, GSH-Rx, SOD, catalase, total protein and albumin was recorded. On the other hand, chicory-supplemented diet succeeded to modulate these observed abnormalities resulting from nitrosamine compounds as indicated by the reduction of TBARS and the pronounced improvement of the investigated biochemical and antioxidant parameters. So, it could be concluded that chicory has a promising role and it worth to be considered as a natural substance for ameliorating the oxidative stress and hepatic injury induced by nitrosamine compounds.

Insulin is a Two-Edged Knife on the Brain

Insulin, long known as an important regulator of blood glucose levels, plays important and multifaceted roles in the brain. It has been reported that insulin is an important neuromodulator, contributing to several neurobiological processes in particular energy homeostasis and cognition. Dysregulation of insulin signaling has been linked to aging and metabolic and neurodegenerative disorders. The first part of this review is devoted to discussion of the critical role of insulin signaling in normal brain function. Then the involvement of impaired insulin signaling in the pathophysiology of diabetes, Alzheimer's, Parkinson's and Huntington's diseases and amyotrophic lateral sclerosis will be discussed. Finally, the potential therapeutic effect of insulin and insulin sensitizers will be examined.

Esophageal cancer associated with chronic mucocutaneous candidiasis. Could chronic candidiasis lead to esophageal cancer?

Chronic mucocutaneous candidiasis (CMC) is a rare disease associated with immunodeficiency and characterized by persistent and refractory infections of the skin, appendages and mucous membranes caused by members of the genus Candida. Several different disorders are classified under this common denominator, including chronic and recurrent mucocutaneous infections due to Candida spp., which are sometimes linked to autoimmune endocrinopathies. These fungal infections are usually confined to the mucocutaneous surface, with little propensity for systemic disease or septicemia. We describe a patient with CMC who had an esophageal candidiasis refractory to treatment for decades and who developed an epidermoid esophageal cancer. No risk factors such as familiar susceptibility, smoking, alcohol drinking, or living in an endemic area were verified. This case report suggests the participation of nitrosamine compounds produced by chronic Candida infections as a risk factor for esophageal cancer in a patient with autosomal-dominant chronic mucocutaneous candidiasis.

Molecular modeling of nitrosamines adsorbed on H-ZSM-5 zeolite: An ONIOM study

Binding energies of nitrosamine compounds, N-nitrosamine (NA), N-methyl-N-nitrososamine (NMA), N-ethyl-N-nitrososamine (NEA), N,N-dimethyl-N-nitrosoamine (NDMA), N-ethyl-N-methyl-N-nitrosoamine (NEMA) and N,N-diethyl-N-nitrosoamine (NDEA) on the H-ZSM-5 zeolite were obtained using the ONIOM(B3LYP/6-31G(d):AM1) approach. Based on amino and imino isomers of nitrosamines, there are two adsorption configurations on the H-ZSM-5 for NA (as NA_a and NA_i), NMA (as NMA_a and NMA_i) and NEA (as NEA_a and NEA_i). The relative binding energies of nitrosamines are in order: NA_a > NMA_a approximately NEA_a > NA_i > NMA_i approximately NEA_i > NEMA approximately NDEA > NDMA. The order of adsorption selectivity for nitrosamines of the H-ZSM-5 is NA_a approximately NA_i >> NMA_a approximately NEA_a > NDMA approximately NMA_i approximately NEMA > NDEA approximately NEA_i. The selective recognition of the NA by the H-ZSM-5 was obviously found.

Diethylnitrosamine-induced hepatocarcinogenesis in rats: possible chemoprevention by blueberries

Nitrosamine compounds are known hepatic carcinogens. This study was designed to study the efficacy of dietary supplementation with blueberries (BB) on diethylnitrosamine (DEN)-initiated hepatocarcinogenesis in male wistar rats. Rats were divided into three groups. The first group served as normal control group, the second group received DEN at a dose of 10 mg/kg body weight five times a week for 15 weeks. The third one received DEN as in DEN-treated group simultaneously with 4% BB-supplemented diet. The results showed that BB caused significant decrease in the elevated serum levels of α-fetoprotein (AFP), homocysteine (Hcy) along with levels of glutathione(GSH), deoxyribonucleic acid (DNA), ribonucleic acid (RNA)and activity of glutathione reductase (GR) in liver. Normalization of elevated α2-macroglobulin (α2M) and total antioxidant capacity (TAC) levels in serum, hepatic glutathione-S-transferase (GST), glutathione peroxidase (GPx) activities and liver weight was achieved whereas body weight was significantly decreased. Moreover, no significant change was observed in elevated relative liver weight, hepatic glucose-6-P-dehydrogenase (G6PD), lactate dehydrogenase (LDH) along with serum aminotransferases, alkaline phosphatase (ALP) and γ-glutamyltransferase (γ-GT) activities. Significant increase in reduced hepatic activity of xanthine oxidase (XO) was achieved and histopathological damage was minimized in BB-treated group. It is suggested that BB suppress DEN- induced hepatocarcinogenesis and could be developed as a promising chemopreventive natural supplement for liver cancer. Key words: Blueberries, diethylnitrosamine, hepatocarcinogenesis, α2-macroglobulin, α-fetoprotein, homocysteine, glutathione, rats.

Protective role of Vitamin E pre-treatment on N-nitrosodiethylamine induced oxidative stress in rat liver

Nitrosamine compounds are known hepatic carcinogens. In the metabolism of nitrosamines, such as N-nitrosodiethylamine (NDEA), there is evidence of the formation of reactive oxygen species (ROS) resulting in oxidative stress, which may be one of the factors in the etiology of cancer. The formation of ROS may alter the antioxidant system, while the presence of Vitamin E may counteract NDEA induced oxidative stress. This study was planned to determine whether pre-treatment with Vitamin E (40 mg/kg body weight, i.p., twice a week for 4 weeks) to NDEA induced rats provides protection against oxidative stress in liver caused by the carcinogen. A single necrogenic dose of NDEA (200 mg/kg body weight) was administered i.p. to the male albino rats with or without Vitamin E pre-treatment and the animals were sacrificed on Days 7, 14 or 21 after the administration of NDEA. The result showed enhanced levels of hepatic lipid peroxidation (LPO) and conjugated dienes of NDEA treated rats as the indices of oxidative stress, however, Vitamin E pre-treated rats administered NDEA showed decreased LPO and conjugated dienes (Day 21). Superoxide dismutase (SOD) activity in liver was not altered significantly in NDEA treated rats with or without Vitamin E pre-treatment. Catalase (CAT) activity was inhibited with NDEA treatment, however, Vitamin E pre-treatment showed recovery in hepatic CAT activity (Days 14 and 21). Total and Se-glutathione peroxidase (GSH-Px) activities and glutathione- S-transferase (GST) activity in liver increased in NDEA treated rats irrespective of Vitamin E pre-treatment. Glutathione reductase (GSH-R) activity as well as total glutathione (GSH) content in liver decreased in NDEA treated animals, both of which were recovered in Vitamin E pre-treated rats administered NDEA. Activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were increased significantly following NDEA treatment to rats with or without Vitamin E pre-treatment. The activities of AST and ALT enzymes were significantly reduced on Days 14 and 21 and ALP activity was reduced on Day 21 in NDEA + Vitamin E treated animals when compared to NDEA treated alone. LDH enzyme activity was normalized on Day 14 in Vitamin E pre-treated animals administered NDEA. However, the AST, ALT and ALP enzyme activities remained high in all treatment groups as compared to control group. Normal control and Vitamin E treated alone rats revealed normal histology of liver. On the other hand, NDEA treated animals showed alterations in normal hepatic histoachitecture, which comprised of necrosis and vacuolization of the cells. However, the rats treated with Vitamin E + NDEA showed that the liver cells were normal, with very little necrosis (Day 21). This study concludes that the pre-treatment with Vitamin E prior to the administration of NDEA, reduced the degree of oxidative stress, although this vitamin produced only slight changes in the hepatic injury, in a time-dependent manner.

Nitrosamine formation from different Catha edulis leaves extracts under simulated gastric condition

Nitrosamines are well-known carcinogenic and toxic compounds for humans and animals. The aim of this study was to investigate the possible formation of nitrosamine compounds from aqueous extracts of five different types of Catha edulis leaves using nitrite as a nitrosation agent, either in aqueous solution or under simulated normal fasting stomach conditions (at 37 °C and pH 2) for 1 h. Nitrosoephedrine was used as a reference compound in this study. Nitrosation of aqueous extracts of the different types of Catha edulis leaves with constant concentration of nitrite (14.4 mM) in aqueous solution showed total apparent nitrosamine compounds to be in the range 94–319 mg/100 g DM (dry matter) of CE ( Catha edulis) leaves. In contrast, nitrosamines formed in simulated gastric fluid were much lower, in the range 23–79 mg/100 g DM of CE leaves. Based on the moderate formation of nitrosamines with the Sabri Catha edulis leaves, the latter was selected for investigating the effect of varying levels of nitrite in aqueous solution and simulated gastric juice. The nitrosation of aqueous extracts of Sabri Catha edulis with different levels of nitrite in aqueous solution yielded a dose-dependent amount of total apparent nitrosamine compounds, these being undetected at ⩽0.5 mM sodium nitrite in aqueous solution and ⩽1 mM in simulated gastric juice. This raises the question of whether the observed high incidence of esophageal and forestomach carcinomas in Yemen could be attributed to the formation of nitrosamines in vivo from the secondary amines present in Catha edulis leaves.

AIM and NBO analyses of N–N rotational barrier in monocyclic nitrosamine compounds

The rotational barrier in monocyclic aliphatic nitroseamines has been examined with the aid of topological theory of atoms in molecules and Weinhold’s natural bond orbital (NBO) analyses. In addition, due to the similarity of the structures of nitrosamines and amides, we have compared the origin of the rotational barrier in nitrosoamine NH 2NO and formamide NH 2CHO compounds. A good correlation between the structural parameters, NBO results, and the properties of charge density has been found.

Restricted rotation in six-membered cyclic nitrosamine compounds: an ab initio and DFT study and NBO analysis

Besides the fact that in nitrosamines, considered as a family of potent carcinogenic compounds, the barrier to internal rotation about the N–N bond is a significant conformational factor, it is as well important for understanding the mechanism of their bioactivity and detoxification. In this work, a detailed study of the internal rotation of the NO group about the N–N bond in various six-membered cyclic nitrosamine compounds was performed using ab initio (HF and MP2) and DFT methods with 6-31G** basis set. Between the two resulting rotational transition states (TS1 and TS2), TS1 was found to be more stable than TS2 according to the all used methods. The activation energy barriers obtained by ab initio methods were also in good agreement with the experimental values. In the studied compound series, the ab initio (HF and MP2) calculated internal rotation activation Gibbs free energies through TS1, lies between 80.01 and 96.26 kJ/mol. The results showed as well that the planar structure of the N-atom in ground state becomes pyramidal in transition states. In addition, in order to explore the origin of the internal rotation energy barrier, the natural bond orbital analysis (NBO) revealed, specifically, that the lp(N4)→BD*(N O) donor–acceptor interaction is the most significant interaction in nitrosamine compounds. NBO analysis showed also that the s-character of the N4 lone pair orbital and its occupation number increases as approaching the top of the rotational barrier in these studied compounds.

Determination of nitrosamines in preserved sausages by solid-phase extraction–micellar electrokinetic chromatography

A new methodology for extraction, pre-concentration and analysis of nitrosamines in meat derived products was developed. The samples (canned sausages) were distilled in vacuum steam and the nitrosamines were pre-concentrated by solid-phase extraction with active carbon. Then, micellar electrokinetic chromatography was used for the separation and determination of the different nitrosamines contained in a real sample and gas chromatography with mass spectrometry detection was used as the confirmation technique. The method allowed the determination of nitrosamine compounds at trace levels with relative standard deviation ranging from 4.0 to 22%.

Restricted rotation in five-membered cyclic nitrosamine compounds: DFT investigation of structural, energetic and kinetics properties

Minimum energy and transition state structures, thermodynamic energies, dipole moments, rotational barrier energies around the N–N bond and also the stability for each of the E and Z isomer forms of some five-membered ring nitrosamines have been determined using density functional theory based method at the B3LYP/6-31G∗ level of theory, using Gaussian 98 package programs. The obtained activation Gibbs free energy of rotation around the N–N bond varies between 51.02 and 112.18kJ/mol in these compounds. The E isomer is generally more stable than the Z isomer except when the hydrogen bonding between NH2 and NO play a stabilizing effect in this molecule. The magnitude of the rotational barrier energy is sensibly affected by the presence of different substituent groups adjacent to the N–NO bond, e.g. for a methyl group adjacent to the N–NO bond the rotational barrier energy is increased while the presence of a carbonyl group adjacent to N–NO, decreases this barrier energy. The DFT results predict also the possibility of separation of some of the E and Z isomer forms in these investigated compounds.