Quantitative analysis of fentanyl in pharmaceutical preparations by gas chromatography-mass spectrometry

Fentanyl (1-[2-phenethyl]-4-N-[N-propionylanilino]piperidine) is a potent synthetic opiate commonly used for surgical analgesia and sedation. Reports of abuse of this highly addictive drug among health care personnel have prompted the need to verify the concentration in the unused portion of single-dose ampules returned to the pharmacy. We describe a simple quantitative method for the analysis of fentanyl citrate (Sublimaze) in syringes returned to the pharmacy following surgery. Fentanyl citrate (0.1 mL) and 2H5-fentanyl (internal standard, 0.05 mL, 100 mg/L) were extracted with Toxi-A tubes (Toxi-Lab, Irvine, CA) and analyzed by gas chromatography-mass spectrometry. Calibration was linear from 1 to 60 mg/L (correlation coefficient of 0.997, n = 13) and had a limit of detection of 0.4 mg/L. Mean recovery at concentrations from 5 to 50 mg/L was 89% (range, 69-104%). No interferences were found with morphine, ketamine, midazolam, sufentanil, or alfentanil. These drugs were not selected for their potential chromatographic interference but for their availability in surgical syringes. This assay is useful in verifying that any unused fentanyl is discarded according to narcotic regulations, thereby avoiding the possibility of diversion for illicit consumption.