title: Validation and uncertainties evaluation of an isotope dilution-SPE-LC-MS/MS for the quantification of drug residues in surface waters.
abstract: The present work describes the development and validation of a reference method conducted at the French National Institute of Metrology (LNE) for the quantitative determination of psychoactive compounds in the dissolved fraction of surface waters. More specifically an isotope dilution-SPE-LC-MS/MS based method has been implemented for the characterization of a broad range of analytes belonging to different classes of psychotropic drugs such as benzodiazepines, antidepressants, stimulants, opiates and opioids, anticonvulsants, anti-dementia drugs, analgesics as well as the anti-inflammatory drug diclofenac in the low ng L(-1) range of concentration. Full validation of the method was performed following procedures described by the French standard NF T90-210. Limits of quantification between 0.14 and 3.54 ng L(-1) were obtained. Method recoveries from 71 to 123% were observed with standard deviation below 10% in intermediate precision conditions. Accuracy was determined for every compound: measurement errors were between -4 and +1% and standard deviations in intermediate precision conditions were included within a 1-9% interval. Finally, measurement uncertainties were evaluated following the Guide to the expression of uncertainty in measurement (GUM). Expanded uncertainties (k=2) ranged from 2% for carbamazepine, EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) and venlafaxine to 17% for diazepam. The validated method was implemented to Seine river surface waters demonstrating its fitness for purpose. All compounds were detected and 22 out of 25 analytes were quantified. More specifically, measured concentration ranged from 0.39 ng L(-1) for MDMA (3,4-methylene-dioxy-N-methylamphetamine) to 182 ng L(-1) for gabapentine.
authors.affiliation: Laboratoire National de Métrologie et d'Essais (LNE), 1 rue Gaston Boissier, 75724 Paris, France; EPOC-UMR 5805 CNRS, Université Bordeaux 1, 351 cours de la Libération, 33405 Talence, France.
authors.forename: V
authors.initials: V
authors.lastname: Brieudes
authors.affiliation: Laboratoire National de Métrologie et d'Essais (LNE), 1 rue Gaston Boissier, 75724 Paris, France. Electronic address: sophie.lardy-fontan@lne.fr.
authors.forename: S
authors.initials: S
authors.lastname: Lardy-Fontan
authors.affiliation: Laboratoire National de Métrologie et d'Essais (LNE), 1 rue Gaston Boissier, 75724 Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Lalere
authors.affiliation: Laboratoire National de Métrologie et d'Essais (LNE), 1 rue Gaston Boissier, 75724 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Vaslin-Reimann
authors.affiliation: EPOC-UMR 5805 CNRS, Université Bordeaux 1, 351 cours de la Libération, 33405 Talence, France.
authors.forename: H
authors.initials: H
authors.lastname: Budzinski
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D004350:Drug Residues / Q000032:analysis* / Q000302:isolation & purification*; D007554:Isotopes; D057230:Limit of Detection; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D035501:Uncertainty; D014867:Water / Q000737:chemistry*; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000302:isolation & purification
chemical_list: D007554:Isotopes; D014874:Water Pollutants, Chemical; D014867:Water
keywords: Illicit drugs; Isotope dilution; Method validation; Metrology; Pharmaceuticals; Surface waters; Uncertainties