Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang 317700, PR China.
Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, PR China.
J Pharm Biomed Anal. 2022 Feb 20;210:114576. doi: 10.1016/j.jpba.2021.114576. Epub 2022 Jan 3.
N-nitrosamines (NAs) are common toxic substances that have a strong correlation with many human diseases, such as liver damage and cancer. However, there is a lack of studies on methods involving the detection of NAs in biological samples, possibly owing to the interference of complex biological matrices and the influence of endogenous NAs. In this work, solid-phase extraction with mixed solid phases and adsorption sedimentation were used to successfully establish a gas chromatography-mass spectrometry (GC-MS) method for detecting eight NAs in rat faeces. Chromatographic separation of analytes was performed with Agilent VF-WAXms (30 m × 0.25 mm, 0.25 µm) GC columns. The LLOQs of eight NAs were set to the concentration of 0.5 ng/g and the obtained standard curves were linear, and correlation coefficients (r) were ≥ 0.99 for samples with concentration ranges of 0.5-500 ng/g. The inter and intra-assay precisions were< 15% for all analytes in the quality control samples, and the accuracies ranged from 88.67% to 108.33%. The extraction recoveries were above 78.56% for seven NAs, and a significant matrix effect was not observed. The application of this method revealed that the levels of NAS in the faeces of rats with colorectal cancer were higher than those of normal rats. Additionally, the effect of a high nitrite diet on NAs in faeces was analysed; the results confirmed that a high nitrite diet might contribute to an abnormal increase in NAs. Our work provides an analytical method for further in vivo study of NAs. Furthermore, a pilot study on the relationship between NAs and colorectal cancer was completed.
N-亚硝胺(NAs)是常见的毒性物质,与许多人类疾病密切相关,如肝损伤和癌症。然而,目前缺乏涉及检测生物样本中 NAs 的方法的研究,这可能是由于复杂的生物基质的干扰和内源性 NAs 的影响。在这项工作中,采用混合固相萃取和吸附沉淀成功建立了一种气相色谱-质谱(GC-MS)法,用于检测大鼠粪便中的八种 NAs。采用 Agilent VF-WAXms(30 m×0.25 mm,0.25 µm)GC 柱对分析物进行色谱分离。八种 NAs 的LLOQ 设置为 0.5 ng/g,所得标准曲线线性良好,浓度范围为 0.5-500 ng/g 的样品相关系数(r)≥0.99。在质控样品中,所有分析物的日内和日间精密度均<15%,准确度在 88.67%至 108.33%之间。七种 NAs 的提取回收率均高于 78.56%,且未观察到明显的基质效应。该方法的应用表明,结直肠癌大鼠粪便中 NAS 的水平高于正常大鼠。此外,还分析了高亚硝酸盐饮食对粪便中 NAs 的影响;结果证实,高亚硝酸盐饮食可能导致 NAs 异常增加。我们的工作为进一步研究 NAs 的体内作用提供了分析方法。此外,还完成了 NAs 与结直肠癌之间关系的初步研究。