Determination Of N-nitrosamines Research Articles

Stir bar sorptive-dispersive microextraction mediated by magnetic nanoparticles-metal organic framework composite: Determination of N-nitrosamines in cosmetic products

A new analytical method based on the recently proposed stir bar sorptive-dispersive microextraction (SBSDME) technique has been developed to determine eight hazardous N-nitrosamines in cosmetic products. As previous step, a simple clean-up is carried out with hexane to remove those highly lipophilic compounds that disturb the SBSDME step. Subsequently, SBSDME is performed by using magnetic nanoparticles–metal organic framework composite, CoFe2O4/MIL-101(Fe), as sorbent to entrap the target analytes, which are later chemically desorbed and measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The experimental variables related to the SBSDME procedure were studied to achieve the highest analytical signal. Under the most favorable conditions, the proposed method was validated providing good linearity; enrichment factors up to 62 depending on the analyte; limits of detection from 3 to 13 µg kg−1; and good repeatability values (RSD < 17.0%). Finally, the method was successfully applied to cosmetic samples composed either of lipophilic or hydrophilic matrices. Quantitative relative recoveries (96–109%) were obtained by using standard addition calibration. The present work expands the applicability of the SBSDME technique, whereas its analytical features make it useful to carry out the quality control of cosmetic samples.

Rapid Identification and Determination of N-Nitrosamines in Food Products by Ultra-High-Performance Liquid Chromatography–High Resolution Quadrupole-Time-of-Flight Mass Spectrometry by Exact Masses of Protonated Molecules

A method is proposed for the rapid identification and determination of seven N-nitrosamines in food products by ultra-high-performance liquid chromatography in combination with high-resolution quadrupole-time-of-flight mass spectrometry. The ranges of detectable concentrations of N-nitrosamines are from 0.001–5 to 2–100 ng/mL for liquid (water, beer) and from 2–50 to 4–100 ng/g for solid (meat, fish, mussels, malt, grain, sausage, wieners, and bockwursts) products. The limits of detection are 0.0005–2 ng/mL, 2–5 ng/g for liquid and solid products, respectively. The recovery of analytes is from 62 to 105%. The matrix effect was estimated in determining N-nitrosamines in samples of different nature. The matrix effect is negligible (≤20%) in the determination of N-nitrosamines in water and is significant for beer, meat products, grain, malt, and fish (>20%). A procedure is proposed for the rapid identification and determination of N-nitrosamines by the standard addition method and using matrix calibration. The relative standard deviation of the results of analysis does not exceed 17%. The duration of sample identification is 40 min; the determination of the detected analytes takes 1–1.5 h.

Determination of N-nitrosamines in water resources using Al-AC sorbent for stir-bar supported micro-solid-phase extraction coupled with gas chromatography mass-spectrometry

This work presents the synthesis of a simple, cheap and an effective sorbent for the extraction of polar nitrosamines from aqueous samples. The sorbent was prepared by the loading of aluminum on activated carbon (Al-AC) and characterized by Fourier transform infrared (FTIR), Raman spectroscopy, and thermogravimetry analysis. The simple sorbent material was then utilized in membrane protected stir-bar supported micro-solid-phase extraction (SB-μ-SPE) to preconcentrate nitrosamines (NA) from various types of aqueous samples. Furthermore, the extracted analytes were analyzed using gas chromatography mass spectrometry. The extraction process parameters were optimized including choosing the best sorbent, mass of that sorbent, time for extraction and desorption, stirring rate during extraction, type of desorption solvent and its volume, and the effect of adding salt to the aqueous sample. The extraction and chromatographic method have shown a wide linear range of 10 to 1000 ng mL−1 with an r2 ranging from 0.9912 to 0.9986. This method can analyze polar nitrosamines with LOD in the range of 0.8 to 3.3 ng mL−1. The reproducibility was tested at three concentration levels from the linear range and found to be in the range of 4.0 to 6.6%. To evaluate the method applicability in a real matrix, the relative recoveries in wastewater, seawater, and drinking water were tested and found to be between 85% and 104.2%.

Determination of N-nitrosamines in Water by Automated Headspace Solid-Phase Microextraction

An automated headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (automated HS-SPME/GC–MS) for the determination of four N-nitrosamines N-nitroso-di-n-ethylamine, N-nitroso-di-n-propylamine, N-nitrosopiperidine and N-nitroso-di-n-butylamine in groundwater samples was developed. Response surface methodology was employed to optimize relevant extraction parameters including extraction time, sample pH, incubation temperature and salt addition. The optimal HS-SPME were 20 min of extraction time, sample pH of 7, incubation temperature of $$65\,{^{\circ }}\hbox {C}$$ and 30% (w/v) sodium chloride concentration. Under these conditions, good linearity for the analytes in the range from 0.1 to $$100\,\upmu \hbox {g}/\hbox {L}$$ with correlation coefficient (R) from 0.975 to 0.992 was obtained. The limits of detection based on a signal-to-noise ratio of 3 were between 0.78 and 11.92 ng/L with corresponding relative standard deviations from 1.8 to 5.7% $$({n}=4)$$ . The average relative recoveries of the four N-nitrosamines from spiked different groundwater samples by $$1\,\upmu \hbox {g}/\hbox {L}$$ and $$20\,\upmu \hbox {g}/\hbox {L}$$ of each analyte (mean ± standard deviation, $$n=4$$ ) were $$96.6\pm 4.4$$ and $$102.3\pm 4.86\,\%$$ , respectively. The method was applied to determine the N-nitrosamine in groundwater samples from different locations in Saudi Arabia. The average recoveries of spiked N-nitrosamines in different groundwater.

Determination of N-nitrosamines in cosmetic products by vortex-assisted reversed-phase dispersive liquid-liquid microextraction and liquid chromatography with mass spectrometry.

A new analytical method for the simultaneous determination of trace levels of seven prohibited N-nitrosamines (N-nitrosodimethylamine, N-nitrosoethylmethylamine, N-nitrosopyrrolidine, N-nitrosodiethylamine, N-nitrosopiperidine, N-nitrosomorpholine, and N-nitrosodiethanolamine) in cosmetic products has been developed. The method is based on vortex-assisted reversed-phase dispersive liquid-liquid microextraction, which allows the extraction of highly polar compounds, followed by liquid chromatography with mass spectrometry. The variables involved in the extraction process were studied to obtain the highest enrichment factor. Under the selected conditions, 75μL of water as extraction solvent was added to 5mL of n-hexane sample solution and assisted by vortex mixing during 30s to form the cloudy solution. The method was successfully validated showing good linearity (0.5-50ng/mL), enrichment factors up to 65 depending on the target compound, limits of detection values of 1.8-50ng/g, and good repeatability (RSD<9.8%). Finally, the proposed method was applied to different cosmetic samples. Quantitative relative recovery values (80-113%) were obtained, thus showing that matrix effects were negligible. The achieved analytical features of the proposed method, besides of its simplicity and affordability, make it useful to perform the quality control of cosmetic products to ensure the safety of consumers.

Determination of N-nitrosamines in water by nano iron-porphyrinated poly(amidoamine) dendrimer MCM-41 generation-3 through solid phase membrane tip extraction and HPLC

Abstract This study described a method comprising solid-phase membrane tip extraction (SPMTE) with nano iron-porphyrinated poly(amidoamine) dendrimer Mobil Composition Matter-41 Generation-3 (FeP-Dend-MCM-41-G3) and high-performance liquid chromatography for analysis of N-nitrosamines in water samples (tap, lake, and hospital water). The studied carcinogenic nitrosamines were N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR), and N-nitrosopiperidine (NPIP). Nano FeP-Dend-MCM-41-G3 SPMTE was evaluated in terms of efficiency for the extraction of nitrosamines from waste, lake, and tap water samples. The suitability of the chromatographic system for the separation of nitrosamines was also established. The capacity factor, k ′ for NMOR, NPYR, and NPIP were 1.67, 2.50, and 6.75, respectively, with excellent selectivity factors (NMOR-NPYR, 1.497 and NPYR-NPIP, 2.70) and resolution, R s (NMOR-NPYR, 1.81 and NPYR-NPIP, 6.00). Under the optimized conditions, the proposed method showed good relative recovery within 84%–100% and acceptable reproducibility with intra- and inter-day relative standard deviations of

Ordered mesoporous carbon as sorbent for the extraction of N-nitrosamines in wastewater and swimming pool water

The analysis and determination of N-nitrosamines (NAs) in water samples are challenging and demanding. In this study, a simple, reliable, and practical methodology is reported for the quantitative determination by gas chromatography-tandem mass spectrometry with electron impact ionization (EI) and triple quadrupole analyzer (GC-EI-MS/MS) of eight NAs after micro-solid-phase extraction (μ-SPE) from wastewater and swimming pool water. Thirty milligram of an ordered mesoporous carbonaceous material, oxidative surface-modified CMK-3, enclosed within a porous polypropylene membrane bag, were used as sorbent for μ-SPE. A central composite design approach was applied to optimize the μ-SPE parameters. An isotopically-labeled NA was used as internal standard. Under the optimized conditions, μ-SPE-GC-EI-MS/MS was validated for an NA concentration range of between 0.1–100ng/mL. The precision of the method was evaluated and an average relative standard deviation of 4.8% (n=8) for a standard solution spiked at 50ng/mL of each NA was obtained. The limits of detection were measured to be in the range of 0.005–0.283ng/mL. Domestic wastewater and swimming pool water samples were used to evaluate the applicability of the method. NAs were detected in swimming pool water and wastewater at concentrations of <2ng/mL and 11ng/mL, respectively.

Development of an analytical method for the determination of N-nitrosamines in tobacco by GC-NCD after solid phase extraction

In this paper an analytical method was developed for the determination of some tobacco specific N-nitrosamines (TSNAs) in cigarettes, and applied to cigarettes purchased in the city of Rio de Janeiro/RJ (Brazil).

Octadecylamine-modified poly (glycidylmethacrylate-divinylbenzene) stationary phase for HPLC determination of N-nitrosamines

Poly (glycidylmethacrylate-divinylbenzene) (Poly (GMA-DVB)) microspheres were prepared by the two-staged swelling and polymerization method, and modified with octadecylamine (ODA) to obtain ODA-poly (GMA-DVB) stationary phase for HPLC. The new material was characterized by scanning electron microscope, nitrogen adsorption-desorption measurement, Fourier transform infrared spectrum, elemental analysis and thermogravimetric analysis. The results showed that poly (GMA-DVB) microspheres had good monodispersity, porosity and ball shapes. The diameters and specific surface area of the microspheres were about 6µm and 396m2g−1, respectively. ODA-poly (GMA-DVB) stationary phase had good thermal stability. Furthermore, the chromatographic performance of the stationary phase was illustrated by separating n-alkylbenzenes, mono-substituted benzenes and N-nitrosamines. Auxiliary quantum chemistry calculation was also carried out to evaluate the interaction mechanism. According to the evaluation, ODA-poly (GMA-DVB) stationary phase exhibited good hydrophobicity and hydrophobic selectivity, strong stereo-selectivity, polar interaction and π-π interaction. The multi-interaction mechanisms could very likely guarantee its excellent chromatographic performance for the analysis of complex samples. Finally, the column was successfully applied in the determination of N-nitrosamines in pickles sample.

Determination of N-nitrosamines in processed meats by liquid extraction combined with gas chromatography-methanol chemical ionisation/mass spectrometry

A simple, accessible and reproducible method was developed and validated as an alternative for the determination of nine volatile N-nitrosamines (NAs) in meat products, using a low volume of organic solvent and without requiring specific apparatus, offering the possibility of practical implementation in routine laboratories. The NAs were extracted with dichloromethane followed by a clean-up with phosphate buffer solution (pH 7.0). The extracts were analysed by gas chromatography-chemical ionisation/mass spectrometry (GC-CI/MS) in positive-ion mode using methanol as reagent. Limits of detection and quantification, recovery and reproducibility were determined for all NAs (N-nitrosodimethylamine, N-nitrosomethylethylamine, N-nitrosodiethylamine, N-nitrosopyrrolidine, N-nitrosodipropylamine, N-nitrosomorpholine, N-nitrosopiperidine, N-nitrosodibutylamine and N-nitrosodiphenylamine). Satisfactory sensitivity and selectivity were obtained even without concentrating the extract by solvent evaporation, avoiding the loss of the nine NAs studied. Limits of detection ranged from 0.15 to 0.37 µg kg−1, whereas limits of quantification ranged from 0.50 to 1.24 µg kg−1. Recoveries calculated in cooked ham that had been spiked at 10 and 100 µg kg−1 were found to be between 70% and 114% with an average relative standard deviation of 13.2%. The method was successfully used to analyse five samples of processed meat products on the day of purchase and 7 days later (after storage at 4°C). The most abundant NAs found in the analysed products were N-nitrosodipropylamine and N-nitrosopiperidine, which ranged from 1.75 to 34.75 µg kg−1 and from 1.50 to 4.26 µg kg−1, respectively. In general, an increase in the level of NAs was observed after the storage period. The proposed method may therefore be a useful tool for food safety control once it allows assessing the profile and the dietary intake of NAs in food over time.

Determination of N-nitrosamines and nicotine in air particulate matter samples by pressurised liquid extraction and gas chromatography-ion trap tandem mass spectrometry

N-nitrosamines are potentially hazardous pollutants, classified as probable carcinogenic and mutagenic by the U.S. Environmental Protection Agency (EPA). In this paper, the presence of these pollutants was studied in air samples taken at different locations of Tarragona (urban and harbour). As a result, a reliable method has been developed for determining N-nitrosamines and nicotine based on pressurised liquid extraction (PLE) and gas chromatography-(chemical ionisation) ion trap tandem mass spectrometry (GC-(CI)MS/MS). The chromatographic analysis enables the determination of these compounds in less than 13min with total separation and good resolution between the compounds. Recovery values were higher than 80% for most of the compounds and the repeatability of the method was under 18% (5ngm−3, %RSD, n=4). MDLs were between 0.1ngm−3 (NMor and NPip) and 2ngm−3 (NMEA). NMor, NPyr, NPip and nicotine were the most frequent compounds in urban and harbour samples at concentration levels between 0.3ngm−3 (NPyr) and 12.5ngm−3 (nicotine) and between 0.13ngm−3 (NPyr) and 3.8ngm−3 (nicotine), respectively.

Liquid chromatography-tandem mass spectrometry determination of N-nitrosamines released from rubber or elastomer teats and soothers

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method as an alternative to a gas chromatography-thermal energy analyser (GC-TEA) method recommended by the European Committee on Standardization (CEN) was validated for the simultaneous determination of eight N-nitrosamines released into artificial saliva from rubber or elastomer teats and soothers. N-nitroso-dipropylamine-d14 (NDPA-d14) was used as internal standard for accurate quantification. The method was validated with relatively good analytical results, including sufficiently low limits of detection (0.1–2 µg kg−1 of sample) and good linearity (r 2 > 0.99) throughout the studied concentration ranges. Intra- and inter-day precisions expressed with the relative standard deviation (RSD, %) were 3.4–8.0% and 4.4–11.3%, which were below the performance criteria based on one-half of the value derived from the Horwitz value. It was also found that the LC-MS/MS method is sufficiently rugged and successfully applicable to its routine analysis for the compliance test of Commission Directive 93/11/EEC.

The determination of N-nitrosamines in food

Introduction N-nitrosamines are formed in food as a result of natural chemical interactions, but mainly through food processing activity. Most are potent carcinogens and their determination is therefore of considerable importance. They exist in various chemical forms and have been measured by colorimetric and spectroscopic methods following gas or liquid chromatography or as a total N-nitroso group by measurement of chemically released nitric oxide. Objectives To provide an overview of the available methods for the analysis of N-nitrosamines in food that includes recently developments. Methods The literature was reviewed from the discovery of the N-nitrosamine problem and the introduction on the N-nitroso-specific detector. Results The evaluation shows that analytical detection methods for volatile N-nitrosamines in food have changed little since the introduction on the N-nitroso-specific detector and that research into the occurrence and formation of both non-volatile N-nitrosamines and the apparent total N-nitroso content (ATNC) have declined. Methods for measuring the apparent total N-nitroso content have not been improved significantly in recent years. Conclusion Modern sample extraction techniques and mass spectrometric methods for the volatile N-nitrosamines have been applied more extensively to water analysis and offer a good opportunity to improve the determination of these carcinogens in food and make the analysis more widely available. Developments in liquid chromatography-mass spectrometry should provide an avenue for renewed interest in non-volatile N-nitrosamines, and could help with the identification of novel compounds whose presence is suggested by the high apparent total N-nitroso content of some foods.

Automatic screening method for the preconcentration and determination of N-nitrosamines in water

A screening method was developed to discriminate among water samples contaminated or uncontaminated with N-nitrosamines in order to reduce the use of expensive instruments such as chromatographs. The system is based on the preconcentration of the analytes onto a sorbent column, elution and derivatization to form nitrite, then formation of a coloured product (Griess reaction) and photometric detection. The limit of detection achieved for 100 ml of sample volume was 0.2 μg/l and the sample frequency 3 h −1. The reliability of the proposed method of the N-nitrosamines was established at five concentrations (between 0.5 and 3 times the limit of detection). For a level concentration of 0.6 μg/l (three times the limit of detection), the percentage of false negatives is 0%. The method was applied to the screening of several water samples (river, pond, well, tap and waste) with a positive response only for waste water samples.

Determination of N-nitrosamines in latex by sequential supercritical fluid extraction and derivatization

A new method to determine N-nitrosamines in latex products has been developed by combination of supercritical fluids and chemical derivatization. A new design for a liquid trap has been introduced. A factorial fractional design was used in order to evaluate the influence of the different factors affecting the process. Factors such as pressure, temperature, static and dynamic time, restrictor temperature and volume of an hydrobromic acid–acetic anhydride mixture (1:10, v/v) were included in the design. CO 2 was used as the extraction fluid. Gas chromatography with nitrogen and phosphorus sensitive detection was employed to achieve good sensitivity attending to the molecular structure of these compounds ( N-nitrosamines and their corresponding secondary amines). The obtained results have shown to be useful to increase selectivity and reduce sample handling.

Optimization of parameters for the supercritical fluid extraction in the determination of N-nitrosamines in rubbers

The study of the possibilities of supercritical fluid extraction (SFE) with N-nitrosamines in rubbers has been carried out. Home-made materials fortified with several N-nitrosamines were prepared in order to optimize the SFE parameters. A Plackett–Burman design was employed to evaluate the influence of those parameters to be controlled in SFE, such as pressure, temperature, static and dynamic time, restrictor temperature and volume of modifier while CO 2 was used as the extraction fluid. An extra central composite design for the main factors (according to the previously obtained results) was also developed in order to refine the best supercritical conditions for the extraction of N-nitrosamines from rubbers. Gas chromatography with a nitrogen and phosphorus sensitive detector was used to achieve sensitivity and limits of detection for the concentrations expected in plastic materials. The proposed analytical method has shown to be useful in the determination of N-nitrosamines even for complex matrices.

High-performance liquid chromatography with post-column chemiluminescence detection for simultaneous determination of trace N-nitrosamines and corresponding secondary amines in groundwater

A sensitive, selective and reliable high-performance liquid chromatographic method with chemiluminescence detection is described for the determination of trace N-nitrosamines and corresponding secondary amines simultaneously in environmental water samples. The method combines solid-phase extraction on to a mini activated carbon column, followed by elution with acetone and concentration of the extracts by denitrosation and fluorogenic derivatization. The separation of derivatives was performed on a C18 column (3µm, 83 × 4.6 mm id) with a mobile phase consisting of acetonitrile-water-ethanol (63.5 + 35.5 + 1.0 v/v) containing 3.0 mmol l–1 imidazole and 0.5 mmol l–1 oxalic acid and with a pH of 6.2. Peroxyoxalate chemiluminescence detection was carried out by using bis(2-nitrophenyl) oxalate and hydrogen peroxide as chemilumigenic reagents. The quantitative data obtained (calibration graphs, detection limits, etc.) were analogous to those published previously. Groundwater samples were analysed using the proposed method. Data including the total amounts of secondary amines plus N-nitrosamines, the amount of secondary amines and results of blank experiments from the chromatograms for individual water sample were calculated, then the final concentrations of N-nitrosamines and secondary amines in each water sample were obtained simultaneously. The application of this procedure for determination of N-nitrosamines and corresponding secondary amines in water samples at pmol l–1 and fmol l–1 levels was successfully achieved. The recoveries of various N-nitrosamines and secondary amines added to groundwater samples were excellent (95% for all except two).

InternationalN‐nitroso compounds check sample programme: Report on the performance in the second study dedicated to their determination in beer and malt

The second check sample survey for the determination of N-nitrosamines in beer and malt has been initiated. Each laboratory received four samples: two beer, from the same batch, spiked respectively with 0.5 microgram/l N-nitrosodimethylamine (NDMA) and 4 micrograms/l NDMA plus 30 micrograms/l N-nitrosoproline (NPRO) and two naturally contaminated malts. Sixteen laboratories sent their results and two apologized in view of analytical problems. Results from this have been statistically evaluated. Comparison to those from the previous study demonstrated a distinct improvement in the results from the analysis of NDMA in beer and malt. Little has been achieved for the other two common contaminants of beer and malt, N-nitrosopyrrolidine (NPYR) and NPRO. For this latter compound in beer, however, some hope came from the data produced by the method of Sen et al. (1983), but the number of results is insufficient to allow firm conclusions to be drawn.

The determination of N-nitrosamines in foods and cosmetics

The discovery that N-nitrosamines are carcinogenic prompted a great deal of research activity in the measurement, occurrence and significance of N-nitroso compounds. As a result, an adequate methodology has been developed for their analysis, although some problems remain to be solved.

Determination of N-nitrosamines by high-performance liquid chromatographic separation with voltammetric detection

The highly polar, nonvolatile N-nitrosamines, N-nitrosoproline and N-nitrosodiethanolamine, are determined by high-performance liquid Chromatographic separation with electrochemical detection using d.c. voltammetry, normal pulse voltammetry, and differential pulse voltammetry. The influence of flow rate and pulse time are determined, and detection limits on the order of 10 -7 M are obtained.