title: Manganese speciation in human cerebrospinal fluid using CZE coupled to inductively coupled plasma MS.
abstract: The neurotoxic effects of manganese (Mn) at elevated concentrations are well known. This raises the question, which of the Mn species can cross neural barriers and appear in cerebrospinal fluid (CSF). CSF is the last matrix in a living human organism available for analysis before a compound reaches the brain cells and therefore it is assumed to reflect best the internal exposure of brain tissue to Mn species. A previously developed CE method was modified for separation of albumin, histidine, tyrosine, cystine, fumarate, malate, inorganic Mn, oxalacetate, alpha-keto-glutarate, nicotinamide-dinucleotide (NAD), citrate, adenosine, glutathione, and glutamine. These compounds are supposed in the literature to act as potential Mn carriers. In a first attempt, these compounds were analyzed by CZE-UV to check whether they are present in CSF. The CZE-UV method was simpler than the coupled CZE-inductively coupled plasma (ICP)-dynamic reaction cell (DRC)-MS method and it was therefore chosen to obtain a first overview information. In a second step, the coupled method (CZE-ICP-DRC-MS) was used to analyze, in detail, which of the compounds found in CSF by CZE-UV were actually bound to Mn. Finally, 13 Mn species were monitored in CSF samples, most of them being identified: Mn-histidine, Mn-fumarate, Mn-malate, inorganic Mn, Mn-oxalacetate, Mn-alpha-keto glutarate, Mn-carrying NAD, Mn-citrate and Mn-adenosine. By far the most abundant Mn species was Mn-citrate showing a concentration of 0.7 +/- 0.13 microg Mn/L. Interestingly, several other Mn species can be related to the citric acid cycle.
authors: GSF-National Research Center for Environment and Health, Institute of Ecological Chemistry, Neuherberg, Germany. bernhard.michalke@gsf.de
authors: Bernhard
authors: B
authors: Michalke
authors: Achim
authors: A
authors: Berthele
authors: Panos
authors: P
authors: Mistriotis
authors: Maria
authors: M
authors: Ochsenkühn-Petropoulou
authors: Stefan
authors: S
authors: Halbach
mesh_terms: D002951:Citrates / Q000134:cerebrospinal fluid; D019075:Electrophoresis, Capillary / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D008345:Manganese / Q000134:cerebrospinal fluid*; D017895:Manganese Compounds / Q000134:cerebrospinal fluid* / Q000737:chemistry* / Q000302:isolation & purification; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D002951:Citrates; D017895:Manganese Compounds; D008345:Manganese