Development and validation of a LC-MS/MS method for analysis of fentanyl and its analogs in stamps

Fentanyl is a synthetic opioid, 50-100 times stronger than morphine. These powerful effects are also observed in the fentanyl analogues, which presents similar chemical structure. The human consume of these molecules may produce psychoactive effects have been associated with cases of deaths worldwide. The goal of this work was the development and validation of a method based on LC-MS/MS to quantify fentanyl, acetylfentanyl, acetyl-norfentanyl, acrylfentanyl, carfentanyl, furanylfentanyl, tiofentanyl and valerylfentanyl in samples of stamps. The LC-MS/MS method was developed using a Force Biphenyl column (1.8 μm and 50 x 2.1 mm) with a specific temperature program in a LCMS-8040 (Shimadzu, Kyoto, Japan) coupled with electrospray ionization, using the multiple reaction monitoring (MRM) mode, totaling 4 min for each run (Figure 1). Fentanyl-d5 was used as internal standard and the validation was based on international guidelines for illicit drug analysis. The method was also found to be linear from 1 to 100 ng/mL for all eight compounds. The imprecisions (intraday and interday %RSD) and accuracy bias (%) were satisfactory at both quality control concentrations, with no more than 10% of RSD. The recovery rates were found between 94-105%. In the real stamps samples analysis, we have quantified 0.58-2.17 mg/blotter of furanylfentanyl. In the best of our acknowledgment, we have developed the first LC-MS/MS method to analyze fentanyl analogs with application in real samples of stamps collected in São Paulo-SP, Brazil.