title: Highly sensitive gas chromatographic-mass spectrometric screening method for the determination of picogram levels of fentanyl, sufentanil and alfentanil and their major metabolites in urine of opioid exposed workers.
abstract: Highly sensitive and specific analytical GC-MS procedures were developed and comprehensively validated for the determination of the opioid narcotics fentanyl, sufentanil and alfentanil and their major nor-metabolites in urine of potentially exposed opioid production workers. A simple, one step extraction protocol was developed using commercially available solid phase extraction (SPE) columns to recover all analytes from urine. The secondary amine functionalities of the nor-metabolites were derivatized to form stable, pentafluorobenzamide (PFBA)-derivatives with good chromatographic properties. Using the penta-deuterated analogues as internal standards, a limit-of-detection (LOD) of 2.5 pg fentanyl/ml, 2.5 pg sufentanil/ml and 7.5 pg alfentanil/ml urine was achieved. For the opioid metabolites the LODs were found to be <50 pg/ml urine. The developed analytical procedures show excellent intra-assay accuracy, particularly considering the ultra low levels of the analytes, with relative errors generally below 10%. Overall, an excellent reproducibility was observed with coefficients of variation below 10% at all spike levels for all opioid parent compounds and their metabolites, except for low norfentanyl concentrations. Upon storage at -30 degrees C urine samples were found to be stable for at least 2 months as no significant losses of either compound were observed. The developed analytical procedures have been successfully applied in a biological monitoring survey of fentanyl exposed production workers.
authors.affiliation: Department of Occupational, Katholieke Universiteit Leuven, Environmental and Insurance Medicine, Laboratory for Occupational Hygiene and Toxicology, Kapucijnenvoer 35, 6th floor, B-3000 Leuven, Belgium. nadine.vannimmen@med.kuleuven.ac.be
authors.forename: Nadine F J
authors.initials: NF
authors.lastname: Van Nimmen
authors.forename: Katrien L C
authors.initials: KL
authors.lastname: Poels
authors.forename: Hendrik A F
authors.initials: HA
authors.lastname: Veulemans
mesh_terms: D000328:Adult; D015760:Alfentanil / Q000652:urine*; D000701:Analgesics, Opioid / Q000652:urine*; D002138:Calibration; D005283:Fentanyl / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D016273:Occupational Exposure; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017409:Sufentanil / Q000652:urine*
chemical_list: D000701:Analgesics, Opioid; D015760:Alfentanil; D017409:Sufentanil; D005283:Fentanyl