Identification and monitoring of fentanyls-related substances in east China sewage water samples by LC-MS for drug enforcement.

Fentanyls abuse is a persistent international concern. New fentanyl derivatives are constantly appearing, circumventing national and international laws. In this study, laboratory degradation experiment with different conditions such as pH, light, temperature and oxygen availability were compared to improve the understanding of the fentanyls degradation pathways. Twelve major degradants of sufentanil and alfentanil were detected and identified together using UHPLC-QTOF-MS. A total of thirty nine fentanyls including twelve typical fentanyl new psychoactive substances, eighteen manufacturing process-related substances and nine key degradants of sufentanil and alfentanil were screened in 120 sewage water samples collected from 20 sewage water treatment plants chosen among 6 urban cities in east China from July to August in 2020 using a validated UHPLC-MS/MS method. Three fentanyls (fentanyl, sufentanil, alfentanil), seven degradants and six manufacturing process-related substances were found in the test samples. The study could provide a useful tool for the monitoring of the abuses, illegal manufacturing or pharmaceuticals related pollutions of fentanyls and their analogs.

Impurity profiling of alfentanil hydrochloride by liquid chromatography/quadrupole time-of-flight high-resolution mass spectrometric techniques for drug enforcement.

RATIONALE: Fentanyl and its analogues play important roles in the hospital and clinic setting as anesthetics. However, illicitly manufactured fentanyl as well as the new psychoactive substances (NPS) account for 30% of all deaths in the United States. Since fentanyl derivatives and NPS are designed to produce similar effects, their related substances are similar or even have the same active groups. A comprehensive analysis of the related substances of alfentanil hydrochloride can provide a basis for the identification and supervision of fentanyl derivatives and NPS. METHODS: A liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (LC/QTOF-MS/MS) method was developed for the separation and characterization of related substances in alfentanil hydrochloride. Degradation studies were conducted according to the ICH-prescribed stress conditions. The compounds were identified mainly through positive electrospray ionization QTOF high-resolution mass spectrometric measurements of the accurate masses of the precursor and product ions and their calculated elemental compositions. Their formation mechanisms were also discussed. RESULTS: Seventeen related substances were detected in alfentanil hydrochloride and its stressed samples. Among them, nine were process-related substances and the other eight were degradation products. The stress study results demonstrated that alfentanil hydrochloride was unstable under acid, alkaline, and oxidative stress conditions, while relatively stable under dry photolytic and thermal stress conditions. Alfentanil hydrochloride was most susceptible for degradation at the N-phenylpropanamide and piperidine sites. CONCLUSIONS: Process-related alfentanil hydrochloride compounds are useful for determination of synthetic routes and entangling of fentanyl analogues. The stress study results can provide a sound scientific basis for the waste water monitoring of alfentanil. These results are important for routine quality control in the manufacturing and storage of alfentanil hydrochloride, as well as for drug enforcement of fentanyl and its analogues.