Fentanyl Analog Screening using LC-TIMS-TOF MS/MS

Area of Science:

• Forensic Chemistry
• Analytical Chemistry
• Toxicology

Background:

• Fentanyl and its analogs are a major cause of overdose deaths in the United States.
• Illicitly manufactured fentanyl's extreme potency contributes to most recent overdose cases.
• There is a growing need for rapid and comprehensive analytical methods to detect these substances.

Purpose of the Study:

• To develop a high-throughput analytical protocol for screening fentanyl analogs.
• To enable the separation and identification of numerous fentanyl analogs from complex samples.
• To provide a reliable method for forensic and toxicological analysis.

Main Methods:

• Utilized a combination of liquid chromatography (LC), trapped ion mobility spectrometry (TIMS), and tandem mass spectrometry (MS/MS).
• Employed data-dependent acquisition (DDA) and data-independent acquisition (DIA) strategies.
• Incorporated parallel accumulation in the mobility trap followed by sequential collision-induced dissociation (CID) fragmentation.

Main Results:

• Successfully separated and assigned hundreds of fentanyl analogs in a single sample and scan.
• Achieved confident analog identification based on retention time, ion mobility, and MS/MS fragmentation patterns.
• Demonstrated the protocol's effectiveness for high-throughput screening.

Conclusions:

• The developed LC-TIMS-MS/MS protocol offers a powerful tool for detecting and identifying fentanyl analogs.
• This method can significantly aid in monitoring the evolving landscape of synthetic opioids.
• The protocol supports forensic investigations and public health efforts to combat overdose epidemics.