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      Position of chromatographic techniques in screening for detection of drugs or poisons in clinical and forensic toxicology and/or doping control

      Clinical Chemistry and Laboratory Medicine (CCLM)
      Walter de Gruyter GmbH

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          Abstract

          This paper reviews chromatographic screening procedures for simultaneous detection of several drug classes relevant to clinical and forensic toxicology or doping control in urine or blood using gas chromatography-mass spectrometry (GC-MS), liquid chromatography coupled with a diode-array detector (LC-DAD) or a mass spectrometer (LC-MS). The pros and cons of the different techniques and procedures are discussed leading to the following conclusions and perspectives. GC-MS, especially in the electron ionization full-scan mode, is still the method of choice for comprehensive screening providing best separation power, specificity and universality, although requiring derivatization. LC-DAD is also often used for screening, but its separation power and its specificity are still inferior to those of GC-MS. Finally, LC-MS has shown to be an ideal supplement, especially for the detection of more polar, thermolabile and/or low-dose drugs, especially in blood plasma. It may become the gold standard in clinical and forensic toxicology and doping control if, at a later date, the costs of the apparatus will be markedly reduced, the current disadvantages like irreproducibility of fragmentation, reduction of ionization by matrix, etc. will be overcome, and finally if one of the increasing number of quite different techniques will become the apparatus standard.

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          Matrix effect in bio-analysis of illicit drugs with LC-MS/MS: influence of ionization type, sample preparation, and biofluid.

          The purpose of the present work was to evaluate the synergistic effect of ionization type, sample preparation technique, and bio-fluid on the presence of matrix effect in quantitative liquid chromatography (LC)-MS/MS analysis of illicit drugs by post-column infusion experiments with morphine (10-microg/mL solution). Three bio-fluids (urine, oral fluid, and plasma) were pretreated with four sample preparation procedures [direct injection, dilution, protein precipitation, solid-phase extraction (SPE)] and analyzed by both LC-electrospray ionization (ESI)-MS/MS and LC-atmospheric pressure chemical ionization (APCI)-MS/MS. Our results indicated that both ionization types showed matrix effect, but ESI was more susceptible than APCI. Sample preparation could reduce (clean up) or magnify (pre-concentrate) matrix effect. Residual matrix components were specific to each bio-fluid and interfered at different time points in the chromatogram. We evaluated matrix effect in an early stage of method development and combined optimal ionization type and sample preparation technique for each bio-fluid. Simple dilution of urine was sufficient to allow for the analysis of the analytes of interest by LC-APCI-MS/MS. Acetonitrile protein precipitation provided both sample clean up and concentration for oral fluid analysis, while SPE was necessary for extensive clean up of plasma prior to LC-APCI-MS/MS.
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            Methcathinone: a new and potent amphetamine-like agent.

            The purpose of the present investigation was to examine the effect of N-monomethylation of phenylisopropylamine derivatives on amphetamine-like activity. In tests of stimulus generalization using rats trained to discriminate 1.0 mg/kg of (+)-amphetamine from saline, the N-monomethyl derivatives of 1-(X-phenyl)-2-aminopropane, where X = 2,4-dimethoxy (2,4-DMA), 3,4-dimethoxy (3,4-DMA), 2,4,5-trimethoxy (2,4,5,-TMA), and 2-methoxy-4,5-methylenedioxy (MMDA-2), did not produce amphetamine-appropriate responding at the doses evaluated. However, the N-monomethyl derivative of cathinone (i.e., methcathinone), like cathinone, resulted in stimulus generalization. Further studies with this agent revealed that (a) in the amphetamine-trained animals, methcathinone (ED50 = 0.37 mg/kg) is more potent than racemic cathinone or racemic amphetamine (ED50 = 0.71 mg/kg in both cases), (b) methcathinone is capable of inducing release of radioactivity from [3H]dopamine-prelabeled tissue of rat caudate nucleus in a manner similar to that observed with cathinone, amphetamine, and methamphetamine, and (c) methcathinone is more potent than cathinone as a locomotor stimulant in mice as determined by their effect on spontaneous activity. The results of the present study provide evidence for a structural analogy between the prototypic psychostimulants amphetamine/methamphetamine and cathinone/methcathinone, and lend further support to the concept that amphetamine and cathinone correspond in their pharmacological effects.
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              Detection Time of Drugs of Abuse in Urine

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                Author and article information

                Journal
                Clinical Chemistry and Laboratory Medicine (CCLM)
                Walter de Gruyter GmbH
                1437-4331
                1434-6621
                January 1 2004
                January 1 2004
                : 42
                : 11
                Article
                10.1515/CCLM.2004.250
                15576292
                6a3cb44b-c03b-45b3-bb77-b9622a0149af
                © 2004
                History

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