Adsorption of N-Nitrosodiethylamine and N-Nitrosodimethylamine on Activated Carbon: A Pre-Concentration Procedure for Gas Chromatographic Analysis

In this study, a rapid pre-concentration procedure, which employs powdered activated carbon as a clean-up and pre-concentration material, is described for the gas chromatographic analysis of N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) in aqueous solutions. It was found that powdered activated carbon is suitable for the adsorption of volatile N-nitrosamine compounds from aqueous solutions. Adsorption efficiency with spiked beer samples (alcohol content 5% v/v) was found to be 80.5% (NDMA) and 89.4% (NDEA) and recovery of extraction from activated carbon was calculated as 82.1% (NDMA) and 89.7% (NDEA), respectively. The effect of 100µgmL^–1 of tannic acid on the adsorption was also studied, and no significant effect on the adsorption and extraction of volatile N-nitrosamine compounds was found.     

Application of capillary electrophoresis-nano-electrospray ionization-mass spectrometry for the determination of N-nitrosodimethylamine in pharmaceuticals

After a presence of highly hepatotoxic and potentially carcinogenic N-nitrosodimethylamine was detected in certain lots of sartan, ranitidine, metformin, and other pharmaceuticals, local regulatory authorities issued recalls of suspected products, and concerns of the pharmacotherapy safety were widely discussed. Since then, testing of a representative sample of each produced lot of these pharmaceuticals is required as a part of quality control processes. Hence, an interface-free CE-nanoESI system coupled with MS detection was employed for the development of a simple and economical method for quantitative detection of this contaminant in the valsartan drug substances and finished formulations used as model matrices. In this arrangement, a fused-silica capillary was used as both a separation column and a nanoESI emitter providing high ionization efficiency and sensitivity. The optimized procedure was found to have sufficient selectivity, linearity, accuracy, and precision. The established LOD and LOQ values were 0.3 and 1.0 ng/mL, respectively. The practical applicability of the method was tested by analyses of commercially available Valsacor^® tablets. The results obtained prove that the developed procedure represents a promising alternative to currently available GC- and LC-based methods. Furthermore, after an adjustment of the separation conditions, the CE-nanoESI/MS system can be conceptually used for the determination of NDMA in other suspected pharmaceuticals.     

Collision induced dissociation of protonated N-nitrosodimethylamine by ion trap mass spectrometry: Ultimate carcinogens in gas phase

Collision induced dissociation of protonated N-nitrosodimethylamine (NDMA) and isotopically labeled N-nitrosodimethyl-d6-amine (NDMA-d6) was investigated by sequential ion trap mass spectrometry to establish mechanisms of gas phase reactions leading to intriguing products of this potent carcinogen. The fragmentation of (NDMA + H⁺) occurs via two dissociation pathways. In the alkylation pathway, homolytic cleavage of the N–O bond of N-dimethyl, N′-hydroxydiazenium ion generates N-dimethyldiazenium distonic ion which reacts further by a CH₃ radical loss to form methanediazonium ion. Both methanediazonium ion and its precursor are involved in ion/molecule reactions. Methanediazonium ion showed to be capable of methylating water and methanol molecules in the gas phase of the ion trap and N-dimethyldiazenium distonic ion showed to abstract a hydrogen atom from a solvent molecule. In the denitrosation pathway, a tautomerization of N-dimethyl, N′-hydroxydiazenium ion to N-nitrosodimethylammonium intermediate ion results in radical cleavage of the N–N bond of the intermediate ion to form N-dimethylaminium radical cation which reacts further through α-cleavage to generate N-methylmethylenimmonium ion. Although the reactions of NDMA in the gas phase are different to those for enzymatic conversion of NDMA in biological systems, each activation method generates the same products. We will show that collision induced dissociation of N-nitrosodiethylamine (NDEA) and N-nitrosodipropylamine (NDPA) is also a feasible approach to gain information on formation, stability, and reactivity of alkylating agents originating from NDEA and NDPA. Investigating such biologically relevant, but highly reactive intermediates in the condensed phase is hampered by the short life-times of these transient species.     

O_(3)/UV多相催化氧化法处理UDMH废水的研究北大核心CSCD

含偏二甲肼(UDMH)的废水在臭氧氧化过程中会显著生成高毒性且难降解的次级氧化产物亚硝基二甲胺(NDMA),采用臭氧/紫外(O_(3)/UV)联用技术仍不能有效抑制NDMA的生成和彻底氧化NDMA.我们以Fe_(2)O_(3)/γ-Al_(2)O_(3)为催化剂,采用多相催化氧化-O_(3)/UV联用技术对含UDMH的废水进行了氧化处理,详细对比了有无催化剂时UDMH的降解效率以及次级氧化产物NDMA生成、氧化消除的规律,结果表明,多相催化技术与O_(3)/UV联用能够显著提高对废水中UDMH的氧化分解效率,且能有效地抑制NDMA的生成和促进NDMA的氧化消除.通过反应参数的优化,确定了最佳的反应条件.在此基础上,对UDMH和NDMA的氧化降解反应动力学进行了对比研究,结果显示,多相催化技术有效提升了NDMA在O_(3)/UV中的氧化降解效率,使得反应所产生的NDMA可以及时分解.我们还对稳定性进行了研究,催化剂经8次循环仍保持较高的催化活性和稳定性.我们的研究结果表明多相催化-O_(3)/UV联用技术对含UDMH废水处理有优良的适用性,综合效能优于现用的O_(3)/UV处理技术.     

气相色谱-质谱法测定含偏二甲肼污水中N-亚硝基二甲胺

采用水蒸气蒸馏、二氯甲烷萃取及氮气吹扫浓缩等样品预处理方法,建立了含偏二甲肼污水中 N-亚硝基二甲胺(NDMA)的气相色谱-质谱(GC-MS)分析方法.以N-亚硝基二甲胺的浓度在0.31～1.54 mg·L-1 范围内对峰面积做校准曲线,回归方程 Y=2.60×104x-4.49×103(r=0.999 5),于 100 mL 蒸馏水(即空白溶液)中分别加入 2.016 μg 及 10.08 μg NDMA,按方法测定并计算回收率及标准偏差,测定结果的相对标准偏差为 4.82%和 4.96%,回收率为 88.8%和89.3%,检出限(S/N=3)为2 μg·L-1.     

超高效液相色谱-静电场轨道阱高分辨质谱法测定法莫替丁及其制剂中的痕量N-亚硝基二甲胺

建立了测定法莫替丁及其制剂中N-亚硝基二甲胺(NDMA)含量的超高效液相色谱-静电场轨道阱高分辨质谱法(UHPLC-Orbitrap HRMS)。样品以甲醇作为提取溶剂,经涡旋混匀、恒温振荡、高速离心、微孔过滤后进行液相色谱-质谱(LC-MS)分析。采用ACE EXCEL 3 C_(18)-AR(150 mm×4.6 mm,3μm)色谱柱,以0.1%甲酸水溶液和0.1%甲酸乙腈为流动相梯度洗脱分离,流速为0.50 mL/min,柱温为30℃,自动进样器温度为4℃,设置六通阀切换保护质谱系统。质谱分析采用ESI离子源,正离子平行反应监测(PRM)扫描模式,外标法定量。NDMA在1.00～100.00 ng/mL范围内线性良好,相关系数(r)为0.999 7,检出限和定量下限分别为0.20 ng/mL和1.00 ng/mL,在法莫替丁及其制剂中的平均回收率为98.5%～108%,相对标准偏差(RSD)为2.3%～6.7%。将该法用于47批供试品中NDMA的测定,在1批法莫替丁原料和2批制剂中检出NDMA,其含量超过限度规定。该方法灵敏、准确、操作简便,可用于法莫替丁及其制剂中NDMA的测定。     

A sensitive method for the determination of nitroamines in alcoholic beverages

Summary Nitrosamines in alcoholic beverages and malted barley were analysed by adsorption from the gas phase onto a porous polymer trap of Chromosorb 104 and subsequent desorption of the trapped compounds directly to a gas chromatograph fitted with glass capillary column and alkali-FID. The detection limit for NDMA was 0.05 g/l in beer samples and 0.3 g/kg in malted barley.Presented at the 14th International Symposium on Chromatography London, September, 1982     

Determination of eight nitrosamines in water at the ng L levels by liquid chromatography coupled to atmospheric pressure chemical ionization tandem mass spectrometry

In this work, we have developed a sensitive method for detection and quantification of eight N-nitrosamines, N-nitrosodimethylamine (NDMA), N-nitrosomorpholine (NMor), N-nitrosomethylethylamine (NMEA), N-nitrosopirrolidine (NPyr), N-nitrosodiethylamine (NDEA), N-nitrosopiperidine (NPip), N-nitroso-n-dipropylamine (NDPA) and N-nitrosodi-n-butylamine (NDBA) in drinking water. The method is based on liquid chromatography coupled to tandem mass spectrometry, using atmospheric pressure chemical ionization (APCI) in positive mode with a triple quadrupole analyzer (QqQ). The simultaneous acquisition of two MS/MS transitions in selected reaction monitoring mode (SRM) for each compound, together with the evaluation of their relative intensity, allowed the simultaneous quantification and reliable identification in water at ppt levels. Empirical formula of the product ions selected was confirmed by UHPLC-(Q)TOF MS accurate mass measurements from reference standards.Prior to LC–MS/MS QqQ analysis, a preconcentration step by off-line SPE using coconut charcoal EPA 521 cartridges (by passing 500 mL of water sample) was necessary to improve the sensitivity and to meet regulation requirements. For accurate quantification, two isotope labelled nitrosamines (NDMA-d₆ and NDPA-d₁₄) were added as surrogate internal standards to the samples.The optimized method was validated at two concentration levels (10 and 100 ng L⁻¹) in drinking water samples, obtaining satisfactory recoveries (between 90 and 120%) and precision (RSD < 20%). Limits of detection were found to be in the range of 1–8 ng L⁻¹. The described methodology has been applied to different types of water samples: chlorinated from drinking water and wastewater treatment plants (DWTP and WWTP, respectively), wastewaters subjected to ozonation and tap waters.     

二甲胺与亚硝酸反应生成N,N-二甲基亚硝胺的理论研究

应用量子化学计算方法在CCSD/6-311＋G(d,p)//B3LYP/6-311＋G(d,p)水平上对二甲胺(DMA)与亚硝酸作用形成N,N-二甲基亚硝胺(NDMA)的反应机理进行了研究. 分别讨论了DMA与一分子亚硝酸直接反应的途径和两分子亚硝酸先反应生成活性中间体N₂O₃再与DMA作用的间接反应途径. 计算结果表明, DMA与亚硝酸间接反应的活化能比直接反应的低约55 kJ/mol, 由此可推断DMA与亚硝酸生成NDMA的反应是以两分子的亚硝酸先生成ONNO₂再亚硝化DMA为主要反应途径. 这一结论和NDMA的形成速率与亚硝酸的浓度的平方成正比的实验结果相一致.