Simultaneous determination of the three major monoamine metabolites in cerebrospinal fluid by high-performance liquid chromatography with electrochemical detection

The technique of isotope dilution mass spectrometry has been used for the measurement of biogenic amine metabolites in cerebrospinal fluid (CSF). CSF samples were collected from rabbits treated with alpha 2-antagonists. The aim of our study was to determine the specificity of these drugs on the central nervous noradrenergic, dopaminergic and serotonergic activity as measured by the release of corresponding monoamine metabolites. 3-Methoxy-4-hydroxyphenylethylene glycol (MHPG) and vanilmandelic acid (VMA) were used as parameters for the noradrenergic activity, whereas homovanillic acid (HVA) and 5-hydroxyindole-3-acetic acid (5-HIAA) were employed to follow the dopaminergic and serotonergic activity, respectively. For the measurement of the biogenic amine metabolites a published GCMS method has been adapted. Samples of 200 microliters CSF were processed. Following addition of deuterated internal standards and acidification, extraction was carried out with ethyl acetate. Preliminary experiments with the analysis of MHPG using diethyl ether for extraction gave rise to emulsion formation and resulted in poor recoveries for MHPG and in irreproducibility problems due to a preferential extraction of non-labelled MHPG, effects which were not observed with ethyl acetate extraction. Derivatization was done with a mixture of pentafluoropropionic anhydride/pentafluoropropanol (or hexafluoroisopropanol) in order to derivatize both hydroxyl and carboxylic acid groups. The derivatization procedure was optimized for the analysis of 5-HIAA by carrying out a second reaction step with pentafluoropropionic anhydride alone in order to complete the derivatization for the indolic NH moiety. The molecular ions of the derivatized products were selected for detection.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected ion monitoring analysis of monoamine metabolites in cerebrospinal fluid. Application to the study ofin vivo effects of α2-antagonists

Dillen

Duchateau

Potter

et al. 1987

Biol. Mass Spectrom.

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Evaluation of parameters for central neuronal activity in cerebrospinal fluid of rabbits following yohimbine

Dillen

Claeys

Potter

1986

Biochemical Pharmacology

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Long-term effects of early social isolation in Macaca mulatta: changes in dopamine receptor function following apomorphine challenge

et al. 1990

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The hypothesis that early social isolation results in long-term alterations in dopamine receptor sensitivity was tested using older adult rhesus monkeys. Isolated and control monkeys were challenged with apomorphine (0.1 and 0.3 mg/kg), and the drug effects on spontaneous blink rate, stereotyped behavior, and self-injurious behavior were quantified using observational measures. Monoamine metabolites were quantified from cisternal CSF by HPLC-EC, prior to pharmacological challenge. Isolated and control monkeys did not differ in CSF concentrations of HVA, 5-HIAA, or MHPG. At the higher dose, apomorphine significantly increased the rate of blinking, the occurrence of whole-body stereotypies, and the intensity of stereotyped behavior (as measured by observer ratings) in isolated monkeys. The frequency of occurrence of self-injurious behavior was too low to allow for meaningful comparisons. These significant differences in response to apomorphine challenge support the hypothesis that long-term or permanent alterations in dopamine receptor sensitivity, as assessed by drug challenge, are a consequence of early social deprivation.

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Simultaneous determination of the three major monoamine metabolites in cerebrospinal fluid by high-performance liquid chromatography with electrochemical detection

Cited by 20 publications

References 25 publications

Selected ion monitoring analysis of monoamine metabolites in cerebrospinal fluid. Application to the study ofin vivo effects of α2-antagonists

Selected ion monitoring analysis of monoamine metabolites in cerebrospinal fluid. Application to the study ofin vivo effects of α2-antagonists

Evaluation of parameters for central neuronal activity in cerebrospinal fluid of rabbits following yohimbine

Long-term effects of early social isolation in Macaca mulatta: changes in dopamine receptor function following apomorphine challenge

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