Department of Chemistry, Illinois State University, Normal, IL, USA.
Chemistry Division, Research Department, Naval Air Warfare Center, Weapons Division (NAWCWD), United States Navy Naval Air Systems Command (NAVAIR), China Lake, CA, USA.
Rapid Commun Mass Spectrom. 2023 Sep;37 Suppl 1:e9493. doi: 10.1002/rcm.9493. Epub 2023 Mar 2.
The burgeoning concern of N-nitrosamine (NAM) contamination found in various pharmaceutical compositions has increased the demand for rapid and reliable screening methods to better assess the breadth of the problem. These carcinogenic compounds are also found in food, water, and soil, and they have been used in poison-related homicides.
A combination of complementary, ambient ionization methods, paper spray ionization (PSI) and filter cone spray ionization (FCSI)-mass spectrometry (MS), was characterized towards trace-level residue screening of select NAMs (e.g., N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodibutylamine) directly from complex and problematic matrices of interest, including prescription and over-the-counter tablets, drinking water, soil, and consumable goods. Spectral data for analyte confirmation and detection limit studies were collected using a Thermo LCQ Fleet ion trap mass spectrometer.
PSI-MS and FCSI-MS readily produced mass spectral data marked by their simplicity (e.g., predominantly protonated molecular ions observed) and congruence with traditional electrospray ionization mass spectra in under 2 min. per sample. Both methods proved robust to the complex matrices tested, yielding ion signatures for target NAMs, as well as active pharmaceutical ingredients for analyzed tablets, flavorants inherent to food products, etc. Low part-per-million detection limits were observed but were shown dependent on sample composition.
PSI-MS and FCSI-MS were successful in detecting trace-level NAMS in complex liquid- and solid-phase matrices with little to no prior preparation. This work suggests that these methodologies can provide a means for assessing problematic pharmaceutical adulterants/degradants for expedited quality control, as well as enhancing environmental stewardship efforts and forensic investigations.
在各种药物制剂中发现的亚硝胺（NAM）污染问题日益受到关注，这促使人们对快速可靠的筛选方法的需求增加，以便更好地评估问题的广泛性。这些致癌化合物也存在于食品、水和土壤中，并且在与中毒有关的杀人案件中被使用过。
本研究采用纸喷雾电离（PSI）和滤膜喷雾电离（FCSI）-质谱（MS）相结合的互补离子化方法，对选定的 NAMs（例如，N-亚硝基二甲胺、N-亚硝基二乙胺、N-亚硝基二丁胺）进行痕量残留筛选，这些 NAMs 直接来自复杂且存在问题的感兴趣基质，包括处方和非处方片剂、饮用水、土壤和消耗品。使用 Thermo LCQ Fleet 离子阱质谱仪收集用于分析物确认和检测限研究的光谱数据。
PSI-MS 和 FCSI-MS 很容易产生质谱数据，其特点是简单（例如，主要观察到质子化分子离子），并且与传统的电喷雾电离质谱在 2 分钟内具有一致性。两种方法都对测试的复杂基质表现出稳健性，为目标 NAMs 以及分析片剂中的活性药物成分、食品产品中固有的香料等产生离子特征。观察到低至 ppm 的检测限，但显示出依赖于样品组成。
PSI-MS 和 FCSI-MS 成功地检测了复杂的液体和固体相基质中的痕量 NAMS，几乎无需事先准备。这项工作表明，这些方法可以为评估有问题的药物掺杂物/降解物提供一种手段，以加快质量控制，以及加强环境管理工作和法医调查。
