Detecting Fentanyl Analogs in Urine Using Precursor Ion Scan Mode

The opioid crisis has led many providers to inquire about the capabilities of urine drug testing (UDT) to detect contemporary compounds such as fentanyl and fentanyl analogs (FAs). However, current methods for clinical UDT, including immunoassays and targeted liquid chromatography tandem mass spectrometry, are not designed to broadly screen for the variety of FAs that may be encountered. In this proof-of-principle study, we developed a precursor ion scan (PIS) method to enable semi-targeted data acquisition for structurally related FAs. Based on the knowledge that many analogs fragment to m/z = 188 and m/z = 105, data were acquired on all precursor ions of 250-400 Da that fragmented to these product ions. Using a tandem mass spectrometer, we analyzed 102 residual urine specimens, in which we identified fentanyl, acetylfentanyl and acrylfentanyl. In 30 contrived urine samples, the PIS was also able to identify furanylfentanyl, butyrylfentanyl, 4-fluoroisobutyrylfentanyl and despropionylfentanyl with accuracy ranging from 83% to 100%.