Mass spectrometry based fragmentation patterns of nitrosamine compounds

Asare, Shardrack O.; Hoskins, Jessica N.; Blessing, Richard A; Hertzler, Russell L.

doi:10.1002/rcm.9261

Cited by 4 publications

(3 citation statements)

References 25 publications

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“…The current N -nitrosamine risk assessment approach − in the pharmaceutical industry consists of paper-based evaluation of synthetic routes and subsequent GC-MS and/or LC-MS analysis − of drug substances and drug products considered to be under risk for N -nitrosamine contamination. The current instrumental analytical methods that can quantify N -nitrosamines in levels below ppm region are time-consuming and expensive, require highly skilled personnel, and require development of the specific analytical method for each individual N -nitrosamine and each drug product.…”

Section: Introductionmentioning

confidence: 99%

Does the Red Shift in UV–Vis Spectra Really Provide a Sensing Option for Detection of N-Nitrosamines Using Metalloporphyrins?

Trampuž¹,

Žnidarič²,

Gallou

et al. 2022

ACS Omega

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N-nitrosamines are widespread cancerogenic compounds in human environment, including water, tobacco products, food, and medicinal products. Their presence in pharmaceuticals has recently led to several recalls of important medicines from the market, and strict controls and tight limits of N-nitrosamines are now required. Analytical determination of N-nitrosamines is expensive, laborious, and time-inefficient making development of simpler and faster techniques for their detection crucial. Several reports published in the previous decade have demonstrated that cobalt porphyrin-based chemosensors selectively bind N-nitrosamines, which produces a red shift of characteristic Soret band in UV–Vis spectra. In this study, a thorough re-evaluation of metalloporphyrin/N-nitrosamine adducts was performed using various characterization methods. Herein, we demonstrate that while N-nitrosamines can interact directly with cobalt-based porphyrin complexes, the red shift in UV–Vis spectra is not selectively assured and might also result from the interaction between impurities in N-nitrosamines and porphyrin skeleton or interaction of other functional groups within the N-nitrosamine structure and the metal ion within the porphyrin. We show that pyridine nitrogen is the interacting atom in tobacco-specific N-nitrosamines (TSNAs), as pyridine itself is an active ligand and not the N-nitrosamine moiety. When using Co(II) porphyrins as chemosensors, acidic and basic impurities in dialkyl N-nitrosamines (e.g., formic acid, dimethylamine) are also UV–Vis spectra red shift-producing species. Treatment of these N-nitrosamines with K2CO3 prevents the observed UV–Vis phenomena. These results imply that cobalt-based metalloporphyrins cannot be considered as selective chemosensors for UV–Vis detection of N-nitrosamine moiety-containing species. Therefore, special caution in interpretation of UV–Vis red shift for chemical sensors is suggested.

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Section: Introductionmentioning

confidence: 99%

Does the Red Shift in UV–Vis Spectra Really Provide a Sensing Option for Detection of N-Nitrosamines Using Metalloporphyrins?

Trampuž¹,

Žnidarič²,

Gallou

et al. 2022

ACS Omega

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“…This database comprises a total of 27,944 nitrosamines collected from various sources: safety assessments of pharmaceutical regulatory agencies, commercial suppliers, and in-silico-generated structures. Fragmentation rules were coded from the literature − and in-house sources and the whole database was fragmented accordingly (more details on the two databases are provided in the Supporting Information).…”

Section: Workflow and Methodsmentioning

confidence: 99%

MARS: A Multipurpose Software for Untargeted LC–MS-Based Metabolomics and Exposomics

Goracci,

Tiberi,

Di Bona

et al. 2024

Anal. Chem.

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Untargeted metabolomics is a growing field, in which recent advances in high-resolution mass spectrometry coupled with liquid chromatography (LC-MS) have facilitated untargeted approaches as a result of improvements in sensitivity, mass accuracy, and resolving power. However, a very large amount of data are generated. Consequently, using computational tools is now mandatory for the in-depth analysis of untargeted metabolomics data. This article describes MetAbolomics ReSearch (MARS), an all-in-one vendor-agnostic graphical user interface-based software applying LC-MS analysis to untargeted metabolomics. All of the analytical steps are described (from instrument data conversion and processing to statistical analysis, annotation/identification, quantification, and preliminary biological interpretation), and tools developed to improve annotation accuracy (e.g., multiple adducts and in-source fragmentation detection, trends across samples, and the MS/MS validator) are highlighted. In addition, MARS allows in-house building of reference databases, to bypass the limits of freely available MS/MS spectra collections. Focusing on the flexibility of the software and its user-friendliness, which are two important features in multipurpose software, MARS could provide new perspectives in untargeted metabolomics data analysis.

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“…In addition, analytical techniques such as HPLC, LC-MS/MS, HR-MS/MS, and GC-MS/MS should be developed for the testing and analysis in detecting and avoiding NMI in herbal products. All herbal products should be tested for the presence of NMI before they are released to the market, and regular testing should be conducted to ensure that NMI does not form over time during the storage of the herbal products [71][72][73][74][75] (▶Fig. 1).…”

Section: Impact and Prevention Strategies For Nitrosamine Impurities ...mentioning

confidence: 99%

Nitrosamine Impurities in Herbal Formulations: A Review of Risks and Mitigation Strategies

et al. 2023

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Nitrosamines are a class of chemical compounds that have been found to be impurities in a variety of pharmaceutical products. These impurities have raised concerns due to their potential carcinogenic effects. Recent studies have identified nitrosamines as impurities in a number of pharmaceutical products including angiotensin II receptor blockers (ARBs) and proton pump inhibitors (PPIs). The presence of nitrosamines in these products has led to recalls and market withdrawals. In addition to pharmaceuticals, nitrosamines have also been found in some herbal medicines particularly those containing traditional Chinese medicinal ingredients. The presence of nitrosamines in herbal formulations poses a significant risk to public health and highlights the need for quality control and regulations in the herbal drug industry. The present review article aims to discuss nitrosamine impurities (NMI) prominent causes, risks and scientific strategies for preventing NMI in herbal formulations. The primary objective of this study is to examine the origins of nitrosamine contamination in herbal formulations, the risks associated with these contaminants, and the methods for reducing them. The significance of thorough testing and examination before releasing herbal products to the public is also emphasized. In conclusion, the presence of nitrosamines is not limited to pharmaceutical products and poses a significant threat to the safety of herbal drugs as well. Adequate testing and extensive research are crucial for producing and distributing herbal medicines to the general population.

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Mass spectrometry based fragmentation patterns of nitrosamine compounds

Cited by 4 publications

References 25 publications

Does the Red Shift in UV–Vis Spectra Really Provide a Sensing Option for Detection of N-Nitrosamines Using Metalloporphyrins?

Does the Red Shift in UV–Vis Spectra Really Provide a Sensing Option for Detection of N-Nitrosamines Using Metalloporphyrins?

MARS: A Multipurpose Software for Untargeted LC–MS-Based Metabolomics and Exposomics

Nitrosamine Impurities in Herbal Formulations: A Review of Risks and Mitigation Strategies

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