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 an important role in hospital and clinic as anesthetic. 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 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 measurement 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 to acid, alkaline, and oxidative stress conditions, while relatively stable under dry photolytic and thermal stress conditions. Alfentanil hydrochloride was most susceptible for degradation in the N-phenylpropanamide and piperidine sites. CONCLUSIONS Process-related alfentanil hydrochloride compounds are useful for determination of synthetic routes and entangling of fentanyl analogs. 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.