title: Highly sensitive capillary electrophoresis-mass spectrometry for rapid screening and accurate quantitation of drugs of abuse in urine.
abstract: The combination of capillary electrophoresis (CE) and mass spectrometry (MS) is particularly well adapted to bioanalysis due to its high separation efficiency, selectivity, and sensitivity; its short analytical time; and its low solvent and sample consumption. For clinical and forensic toxicology, a two-step analysis is usually performed: first, a screening step for compound identification, and second, confirmation and/or accurate quantitation in cases of presumed positive results. In this study, a fast and sensitive CE-MS workflow was developed for the screening and quantitation of drugs of abuse in urine samples. A CE with a time-of-flight MS (CE-TOF/MS) screening method was developed using a simple urine dilution and on-line sample preconcentration with pH-mediated stacking. The sample stacking allowed for a high loading capacity (20.5% of the capillary length), leading to limits of detection as low as 2 ng mL(-1) for drugs of abuse. Compound quantitation of positive samples was performed by CE-MS/MS with a triple quadrupole MS equipped with an adapted triple-tube sprayer and an electrospray ionization (ESI) source. The CE-ESI-MS/MS method was validated for two model compounds, cocaine (COC) and methadone (MTD), according to the Guidance of the Food and Drug Administration. The quantitative performance was evaluated for selectivity, response function, the lower limit of quantitation, trueness, precision, and accuracy. COC and MTD detection in urine samples was determined to be accurate over the range of 10-1000 ng mL(-1) and 21-1000 ng mL(-1), respectively.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva 4, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Kohler
authors.forename: Julie
authors.initials: J
authors.lastname: Schappler
authors.forename: Serge
authors.initials: S
authors.lastname: Rudaz
mesh_terms: D000662:Amphetamines / Q000652:urine*; D003042:Cocaine / Q000737:chemistry; D019075:Electrophoresis, Capillary / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D053610:Opiate Alkaloids / Q000652:urine*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015813:Substance Abuse Detection / Q000295:instrumentation* / Q000379:methods*
chemical_list: D000662:Amphetamines; D053610:Opiate Alkaloids; D003042:Cocaine