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1 It has been reported that co-administration of¯uoxetine with 3,4-methylenedioxymethamphetamine (MDMA,`ecstasy') prevents MDMA-induced degeneration of 5-HT nerve endings in rat brain. The mechanisms involved have now been investigated. 4 A signi®cant cerebral concentration of¯uoxetine plus nor¯uoxetine was detected over the 7 days following¯uoxetine administration. The¯uvoxamine concentration had decreased markedly by 24 h. 5 Pretreatment with¯uoxetine (10 mg kg 71 , 62) failed to alter cerebral MDMA accumulation compared to saline pretreated controls. 6 Neither¯uoxetine or¯uvoxamine altered MDMA-induced acute hyperthermia. 7 These data demonstrate that¯uoxetine produces long-lasting protection against MDMA-induced neurodegeneration, an e ect apparently related to the presence of the drug and its active metabolite inhibiting the 5-HT transporter. Fluoxetine does not alter the metabolism of MDMA or its rate of cerebral accumulation.

Background and aimsIncreased propionylcarnitine levels in newborn screening are indicative for a group of potentially severe disorders including propionic acidemia (PA), methylmalonic acidemias and combined remethylation disorders (MMACBL). This alteration is relatively non-specific, resulting in the necessity of confirmation and differential diagnosis in subsequent tests. Thus, we aimed to develop a multiplex approach for concurrent determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid from the same dried blood spot (DBS) as in primary screening (second-tier test). We also set out to validate the method using newborn and follow-up samples of patients with confirmed PA or MMACBL.MethodsThe assay was developed using liquid chromatography–tandem mass spectrometry and clinically validated with retrospective analysis of DBS samples from PA or MMACBL patients.ResultsReliable determination of all three analytes in DBSs was achieved following simple and fast (<20 min) sample preparation without laborious derivatization or any additional pipetting steps. The method clearly distinguished the pathological and normal samples and differentiated between PA and MMACBL in all stored newborn specimens. Methylcitric acid was elevated in all PA samples; 3-hydroxypropionic acid was also high in most cases. Methylmalonic acid was increased in all MMACBL specimens; mostly together with methylcitric acid.ConclusionsA liquid chromatography–tandem mass spectrometry assay allowing simultaneous determination of the biomarkers 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in DBSs has been developed. The assay can use the same specimen as in primary screening (second-tier test) which may reduce the need for repeated blood sampling. The presented preliminary findings suggest that this method can reliably differentiate patients with PA and MMACBL in newborn screening. The validated assay is being evaluated prospectively in a pilot project for extension of the German newborn screening panel (‟Newborn screening 2020”; Newborn Screening Center, University Hospital Heidelberg).