Identification and quantitation of N-nitrosamines in human postmortem organs

Area of Science:

• Analytical Chemistry
• Toxicology
• Forensic Science

Background:

• Volatile N-nitrosamines are a class of compounds with known carcinogenic potential.
• Their presence in human tissues, particularly postmortem, requires sensitive and selective detection methods.
• Understanding N-nitrosamine distribution in organs is crucial for toxicological and forensic investigations.

Purpose of the Study:

• To develop and validate a highly sensitive and selective gas-liquid chromatographic (GLC) method for quantifying six volatile N-nitrosamines in human postmortem organs.
• To assess the recovery rates of specific N-nitrosamines using the developed method.
• To investigate the distribution of N-nitrosamines in various human organs, including the brain, liver, kidneys, and pancreas.

Main Methods:

• Quantitative determination of six volatile N-nitrosamines (NDMA, NDEA, NDPA, NDBA, NPIP, NPY) using gas-liquid chromatography.
• Employing two detectors: electron capture detector (ECD) and thermal energy analyzer (TEA) for enhanced selectivity and sensitivity.
• N-Nitrosamines were derivatized to N-nitramine analogs using pertrifluoroacetic acid oxidation followed by purification via adsorption chromatography for ECD analysis.
• Direct analysis of N-nitrosamines in organ extracts using the TEA detector without derivatization.

Main Results:

• The method demonstrated good mean absolute percentage recoveries for the analyzed N-nitrosamines, ranging from 54.7% to 80.0%.
• N-Nitrosodimethylamine (NDMA) was ubiquitously detected in all examined postmortem organs.
• N-Nitrosodipropylamine (NDPA) was detected in the liver of only one out of four subjects.
• NDMA was present in all brain samples, confirming its ability to cross the blood-brain barrier.

Conclusions:

• The developed GLC method is effective for the sensitive and selective quantitative determination of volatile N-nitrosamines in human postmortem organs.
• The ubiquitous presence of NDMA in all organs and its detection in the brain highlights potential systemic exposure and neurotoxicological implications.
• The method's ability to avoid artifactual formation of N-nitrosomethyl-N-butylamine (NMBA) enhances its reliability for nitrosation studies.