Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A procedure is described for the rapid determination of the major indoles and catechols. Analysis with picogram detection limits was done by high-pressure liquid chromatography on a C18 reverse-phase column using electrochemical detection (LCEC). This method provides a comprehensive list of compounds which can be simultaneously determined in brain samples and for which there is no necessity of derivatization or pre-column purification. The regional distribution of 9 neurochemicals from rat brain and the levels of 10 neurochemicals from human brain are presented. DOPA, TYR, NE, MHPG, DOPAC, 5-HIAA, TRP, DA, HVA, 3-MT and 5-HT were detected in the caudate nucleus and putamen. The levels of neurochemicals from the caudate and putamen of a demented patient with Parkinson's disease were variably decreased; catechol and indole losses were greatest in the putamen. The levels of neurochemicals in the caudate and putamen of patients with Alzheimer's disease (SDAT) were also variably decreased; loss of NE was seen only in putamen and losses of DA, HVA and 5-HT were uniform across both caudate and putamen. The CSF of SDAT patients showed changes in NE only.
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PMID:Determination of tyrosine, tryptophan and their metabolic derivatives by liquid chromatography-electrochemical detection: application to post mortem samples from patients with Parkinson's and Alzheimer's disease. 396 72

We have developed two HPLC systems for the simultaneous determination of CA, 5-HT and their precursors and metabolites in human body fluid. One system consisted of two reversed-phase columns, a column switching device, a pair of electrodes for elimination of interferents and two sets of new electrochemical detectors with four electrodes. Using this system, adequate separation of peaks for 17 kinds of CA, 5-HT and their related metabolites in a standard solution required only 17 min. NE, MHPG, DOPAC, 5-HIAA, HVA and TRP levels in cerebrospinal fluid (CSF) were determined without any pretreatment of the CSF samples. The concentrations of DOPAC, 5-HIAA and HVA in CSF were significantly lower in Alzheimer's disease, vascular dementia and Parkinson's disease than in the controls. The other system was developed for determination of CA acidic metabolites and 5-HIAA in human urine. This system consisted of a mixed-mode column (C18/anion) and 8-channel electrochemical detector with isocratic elution of citrate buffer. Detection limits, precision and analytical recoveries of this method were satisfactory for clinical use.
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PMID:[Simultaneous determination of catecholamines, serotonin, and their precursors and metabolites in body fluid by an HPLC system with multi-electrode electrochemical detector]. 791 40

Highly chlorinated beta-carbolines have a potential in vivo relevance to Parkinson's disease. In this paper, a gas chromatographic method for the determination of the neurotoxic 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo), the condensation product of tryptamine and chloral hydrate, is described. The specific and sensitive assay involves purification of the biological samples by solid-phase extraction with C18 cartridges, derivatization with heptafluorobutyric anhydride, and chromatography on a non-polar fused-silica capillary column. Detection of TaClo was achieved by the registration of characteristic mass fragments of the TaClo heptafluorobutyric amide derivative using selected ion monitoring. The method was utilized to detect and quantify TaClo in blood, urine, bile, faeces, and brain tissue of rats treated with this alkaloid-type heterocycle. Four-fold deuterium-labelled TaClo was used as an internal standard.
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PMID:Endogenous alkaloids in man. XXVI. Determination of the dopaminergic neurotoxin 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) in biological samples using gas chromatography with selected ion monitoring. 901 56

Apomorphine is a powerful agonist of dopaminergic receptors which several years ago was introduced into the therapy of Parkinson's Disease. The pharmacological activity of apomorphine already appears significant at low doses. Unfortunately, the difficulty in determining the drug in plasma at low concentrations hampers the completion of accurate pharmacokinetic studies in humans. Considering the analogy of apomorphine with the molecular structure of catecholamines, the extraction of the drug from plasma was optimized by using adsorption on alumina, a technique widely used for noradrenaline and adrenaline analysis in clinical chemistry laboratories. This method proved particularly efficient and selective in apomorphine extraction from plasma prior to high-performance liquid chromatographic analysis. After pretreatment of 200 microliters of plasma sample with 40 mg of alumina and 10 microliters of tris buffer (pH 8.6), the drug was eluted with 200 microliters of an acidic-organic solution. One volume of the supernatant was mixed with two volumes of phosphate buffer (pH 3.6), and 100 microliters of the obtained mixture were injected into the HPLC system. The chromatograph was equipped with a C18 reversed-phase column and with an electrochemical coulometric detector fitted with a high-sensitivity cell (first electrode 0.00 volts, second electrode +0.35 volts). Sensitivity (20 pg of injected drug), precision (CV within assay and between assays of 3.7% and 5.6%, respectively) and accuracy were comparable to more complex analytical procedures. The miniaturisation of the entire sample pretreatment proved very advantageous for pharmacokinetics studies and, in principle, for therapeutic drug monitoring and toxicological investigations.
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PMID:Determination of apomorphine in human plasma by alumina extraction and high-performance liquid chromatography with electrochemical detection. 930 67

Analytical methods are described for the selective, rapid and sensitive determination of R- and S-apomorphine, apocodeine and isoapocodeine and the glucuronic acid and sulfate conjugates in plasma and urine. The methods involve liquid-liquid extraction followed by high-performance liquid chromatography with electrochemical detection. The glucuronide and sulfate conjugates are determined after enzymatic hydrolysis. For the assay of R- and S-apomorphine a 10 microm Chiralcel OD-R column is used and the voltage of the detector is set at 0.7 V. The mobile phase is a mixture of aqueous phase (pH 4.0)-acetonitrile (65:35, v/v). At a flow-rate of 0.9 ml min(-1) the total run time is ca. 15 min. The detection limits are 0.3 and 0.6 ng ml(-1) for R- and S- apomorphine, respectively (signal-to-noise ratio 3). The intra- and inter-assay variations are <5% in the concentration range of 2.5-25 ng ml(-1) for plasma samples, and <4% in the concentration range of 40-400 ng ml(-1) for urine samples. For the assay of apomorphine, apocodeine and isoapocodeine, a 5 microm C18 column was used and the voltage of the detector set at 0.825 V. Ion-pairing chromatography was used. The mobile phase is a mixture of aqueous phase (pH 3.0)-acetonitrile (75:25, v/v). At a flow-rate of 0.8 ml min(-1) the total run time is ca. 14 min. The detection limits of this assay are 1.0 ng ml(-1) for apomorphine and 2.5 ng ml(-1) for both apocodeine and isoapocodeine (signal-to-noise ratio 3). The inter-assay variations are 5% in the concentration range of 5-40 ng ml(-1) for plasma samples and 7% in the concentration range of 50-500 ng ml(-1) for urine samples. The glucuronic acid and sulfate conjugates of the various compounds are hydrolysed by incubation of the samples with beta-glucuronidase and sulfatase type H-1, respectively. Hydrolysis was complete after 5 h of incubation. No measurable degradation of apomorphine, apocodeine and isoapocodeine occurred during the incubation. A pharmacokinetic study of apomorphine, following the intravenous infusion of 30 microg kg(-1) for 15 min in a patient with Parkinson's disease, demonstrates the utility of the methods: both the pharmacokinetic parameters of the parent drug and the appearance of apomorphine plus metabolites in urine could be determined.
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PMID:Assay of R-apomorphine, S-apomorphine, apocodeine, isoapocodeine and their glucuronide and sulfate conjugates in plasma and urine of patients with Parkinson's disease. 944 64

Salsolinol is one of the dopamine-derived tetrahydroisoquinolines, supposed to be a potent dopaminergic neurotoxin, similar to MPTP. Its systemic administration induced parkinsonism in monkeys. The aim of the study was to compare the concentration of salsolinol and the metabolite of L-dopa, 3-O-MD, and the metabolite of dopamine, HVA, in the cerebrospinal fluid of patients with different degrees of parkinsonism, treated or nontreated with l-dopa. Lumbar CSF was obtained from 26 patients with Parkinson's disease (15 early and 11 advanced parkinsonism) and from six healthy controls. The presence of salsolinol, HVA and 3-O-MD was assayed with a sensitive HPLC method employing C18 (Hypersil BDS) column. The analysis of the results demonstrated that the concentration of salsolinol was related to the degree of parkinsonism but not affected by l-dopa treatment. In contrast, HVA and 3-O-MD were significantly elevated in patients receiving l-dopa but did not correlate with the severity of parkinsonism. The results suggest that salsolinol in the cerebrospinal fluid does not originate from exogenous l-dopa and its elevation in cerebrospinal fluid may be an indicator of the advancement of parkinsonism.
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PMID:[Salsolinol, 3-O-methyl-dopa and homovanillic acid in the cerebrospinal fluid of Parkinson patients]. 951 52

This paper describes the validation of a micellar electrokinetic capillary chromatography method for the direct determination of the 3-O-glucuronides of entacapone and its (Z)-isomer, the main urinary metabolites of entacapone in humans. Entacapone is a novel drug which, as a potent inhibitor of catechol-O-methyltransferase (COMT), is used as an adjunct in the standard therapy of Parkinson's disease. The 3-O-glucuronide of another COMT inhibitor, nitecapone, was used as internal standard (I.S.). The validation experiments were performed by using spiked urine samples that were extracted with Sep-Pak C18 cartridges before analysis. Determinations were carried out in a buffer of pH 7.0 containing 25 mM of phosphate, 50 mM of borate and 20 mM of sodium dodecyl sulfate, and by applying 15 kV over a 67 cm (60 cm to the detector) x 75 microns fused-silica capillary. UV detection was at 335 nm. The validity of the method was assessed by investigating the identity of the analytes, selectivity, limit of quantitation, linearity, within-day precision, extraction recovery, between-day precision and accuracy, electroosmotic flow stability and analyte stability. The method proved to be reproducible, sufficiently selective and accurate. Extraction recoveries of the analytes were > 94%. The limit of quantitation (LOQ) was 2 micrograms/ml and the assay was linear in the range 2-150 micrograms/ml with correlation coefficients better than 0.999 for both glucuronides. The repeatability of the method, expressed as the ratio of corrected peak area of the analytes to that of I.S., gave RSD values of < 5% even at the LOQ. Between-day precision (RSD) was < 7.5% for both glucuronides at 7.5 micrograms/ml. Determination of the glucuronide concentrations in urine samples of 34 patients treated with entacapone either orally (200 mg) or intravenously (25 mg) showed the method to be suitable for monitoring the concentrations of the glucuronide of entacapone after both oral and intravenous administration and those of the glucuronide of its (Z)-isomer after oral administration. The limited long term stability of the system requires, however, frequent recalibration in applications involving long sample series.
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PMID:Micellar electrokinetic capillary chromatography method for direct determination of glucuronides of entacapone and its (Z)-isomer in human urine. 1022 Sep 13

Ropinirole, 4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-one, is a potent anti-Parkinson's disease drug developed by SmithKline Beecham Pharmaceuticals. Capillary liquid chromatography (CLC) was used for the separation and quantification of ropinirole and its five related impurities, potentially formed during its synthesis. A simultaneous optimization of three mobile phase parameters, i.e., pH, buffer concentration and acetonitrile content was performed employing an experimental design approach which proved a powerful tool in method development. The retention factors of the investigated substances in different mobile phases were determined. Baseline resolution of the six substances on a C18 reversed stationary phase was attained using a mobile phase with an optimized composition [acetonitrile-8.7 mM 2-(N-morpholino)ethanesulfonic acid adjusted to pH 6.0 (55:45, v/v)]. It was shown that CLC, operated in the isocratic mode under the mobile phase flow-rate of 4 microl/min, can determine the level of these impurities, down to a level of 0.06% of the main component within 25 min.
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PMID:Separation and quantification of ropinirole and some impurities using capillary liquid chromatography. 1051 66

Neuromelanin (NM) is a complex polymer pigment found in catecholaminergic neurons of the human brain. The structure, formation pathway, and physiological function of NM have not yet been clarified, but interest in this polymer has been sparked by the suggestion that NM is involved in cell death in Parkinson's disease. In the current study, pyrolysis-gas chromatography/mass spectrometry analysis was applied for structural investigation of NM isolated from the human substantia nigra, using synthetic eumelanin and pheomelanin-type pigments as reference materials. None of the heterocyclic, sulfur-containing compounds being characteristic thermal degradation products of cysteinyldopamine-derived units of synthetic pheomelanin standard was detected in the pyrolysates of natural NM. The results suggest that nigral pigment isolated from normal brain tissue does not contain benzothiazine-type monomer units. Pyrolytic experiments in the presence of a derivatizing agent allowed identification of high levels of saturated and monounsaturated straight-chain C14-C18 fatty acids and led to the conclusion that a part of a lipid component is chemically bound to the NM macromolecule. The nigral pigment was also shown to be tightly associated with an isoprenoid-type compound.
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PMID:GC/MS analysis of thermally degraded neuromelanin from the human substantia nigra. 1514 83

A high performance liquid chromatographic assay for the quantitative determination of apomorphine in human plasma is described. Sample clean-up and concentration was optimised using solid-phase extraction on C18 cartridges, enabling rapid and sensitive determination of apomorphine and potential metabolites. The limit of apomorphine quantification, using fluorescence detection, was 0.5 ng/mL. The assay was stability-indicating, and allowed the detection of analytes in the presence of commonly co-administered anti-Parkinsonian drugs. Apomorphine was stable in frozen plasma containing 0.14% (w/v) ascorbic acid for 98 days, and through four freeze-thaw cycles. The assay has been used in clinical pharmacokinetic studies of apomorphine in patients with Parkinson's disease, and in preliminary studies of novel apomorphine delivery devices in volunteers.
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PMID:Improved assay for R(-)-apomorphine with application to clinical pharmacokinetic studies in Parkinson's disease. 1636 96


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