Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A simple, rapid, and accurate high-performance liquid chromatographic method using fluorescence detection is described for the measurement of ciprofloxacin in plasma, whole blood, and erythrocytes. Ciprofloxacin and the internal standard difloxacin were separated on a mu-Bondapak C18 column (30 cm x 3.9 mm inside diameter, 10 microns particle size), using a mobile phase of 0.1 M phosphate buffer (pH 2.5):acetonitrile (75:25, vol/vol). The retention times were 5.1 min for ciprofloxacin and 7.9 min for difloxacin. The compounds were extracted from the three biological fluids using protein precipitation followed by a single-step liquid-liquid extraction. The assay is precise, with interassay coefficients of variation of less than or equal to 9.1% and an accuracy of less than or equal to 7.4% at 0.5 and 5.0 micrograms/ml (n = 5). The mean extraction recoveries of ciprofloxacin in plasma, whole blood, and erythrocytes were 84.4, 63.9, and 48.0%. The limit of detection for ciprofloxacin is 25 ng/ml. Ciprofloxacin concentrations in the three biological fluids were measured in patients with uncomplicated falciparum malaria to demonstrate the application of the method.
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PMID:Measurement of ciprofloxacin in human plasma, whole blood, and erythrocytes by high-performance liquid chromatography. 192 83

Methods were developed for the production of clinical grade malaria vaccine candidates expressed in E. coli by recombinant DNA technologies. The essential features of the purification protocol consist of (1) mechanical breakage of host cells and solubilization of the recombinant proteins in 6 M guanidine hydrochloride; (2) ammonium sulfate fractionation; (3) affinity chromatography on a Ni(2+)-chelate gel in the presence of 6 M guanidine hydrochloride; and (4) ion exchange chromatograph on a Phospho Ultrogel column in the presence of 6 M urea. The use of undesirable chemicals (PMSF, DFP, TFA, acetonitrile, etc.) was avoided rather than demonstrating their complete removal after the purification steps. Testing of chromatographic fractions for host-cell proteins and the elimination of fractions with E. coli protein content was found necessary to obtain a final product that contained less than 0.01% of host derived proteins. The recombinant proteins were renatured either from 8 M urea or from 6 M guanidine hydrochloride by increasing the pH to 10.5 in the presence of glycine and EDTA, reduction with DTT, dilution to a protein concentration below 1 mg.ml-1, and dialysis against 0.9% NaCl. The method presented here can be tailor-fit, with minor modification, for the purification of almost any recombinant protein and the final product satisfies current regulations concerning the production of clinically acceptable therapeutic products.
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PMID:Preparation of clinical grade proteins produced by recombinant DNA technologies. 194 Mar 92

A reversed-phase high-performance liquid chromatographic method using acetonitrile-methanol-(1M) perchloric acid-water (30:9:0.8:95, v/v/v/v) at a flow of 1.5 ml min-1 on mu-Bondapak C18 column with UV (254 nm) detection has been developed for the separation of sulphadoxine, sulphalene and sulphamethoxazole from other antimalarials. Calibration curves were linear in the range 0.5-100 micrograms ml-1. The limit of quantitation was 50 ng ml-1. Within-day and day-to-day coefficients of variation averaged 2.1 and 6.45%, respectively. The extraction recovery of sulphadoxine from plasma, red blood cells and whole blood was 90.28, 92.05 and 94.69%, respectively. The method has been used for the determination of sulphadoxine concentrations in plasma, red blood cells and whole blood of eight healthy and 50 Plasmodium falciparum malaria cases after administration of two tablets of Fansidar. Mean sulphadoxine concentration in plasma was higher than red blood cells or whole blood. Sulphadoxine concentration in plasma and whole blood of P. falciparum malaria cases was significantly higher as compared to healthy volunteers while it was the same in red blood cells. Sulphadoxine was absorbed much less in red blood cells than in plasma or whole blood.
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PMID:Sulphadoxine concentrations in plasma, red blood cells and whole blood in healthy and Plasmodium falciparum malaria cases after treatment with Fansidar using high-performance liquid chromatography. 784 Dec 29

A selective and sensitive high-performance liquid chromatographic method with electrochemical detection is described for the simultaneous quantitation of primaquine and carboxyprimaquine, its primary metabolite, in plasma. After addition of internal standard, plasma was deproteinized by addition of acetonitrile. Nitrogen-dried supernatants, resuspended in mobile phase were analyzed on a C8 reversed-phase column. Limits of detection for primaquine and carboxyprimaquine were 2 and 5 ng/ml with quantitation limits of 5 and 20 ng/ml, respectively. None of 47 tested antimicrobial agents interfered. In contrast to previously reported methods, the assay sensitivity and specificity are sufficient to permit quantitation of primaquine in plasma for pharmacokinetics following low dose (30 mg, base) oral administration of primaquine, typically used in the treatment of malaria and Pneumocystis carinii pneumonia.
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PMID:Simultaneous determination of primaquine and carboxyprimaquine in plasma using high-performance liquid chromatography with electrochemical detection. 806 37

WR 242511 (or I) is a new compound of the 8-aminoquinoline class designed to replace primaquine for the treatment of malaria. In order to perform preclinical and clinical testing, an assay was needed to determine drug levels in plasma samples. A simple and reliable reversed-phase high-performance liquid chromatographic (HPLC) method for the measurement of I in plasma using oxidative electrochemical detection is described. A 250-microliters plasma sample containing WR 256408 (or II) as internal standard was extracted with tert.-butyl methyl ether-2-propanol. A 25-microliters aliquot of the extractant was used for HPLC analysis. The mobile phase was 50:50 acetonitrile-sodium acetate (50 mM, pH 6) with 1 mM EDTA. Compounds I and II were separated within 10 min. The limit of detection for I was 10 ng/ml (plasma) with a recovery around 72%. The method was validated in a dog experiment where levels were followed for 48 h. The method is sensitive and robust and can be used for routine drug analysis during pharmacokinetic studies.
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PMID:High-performance liquid chromatographic method for the determination of a candidate 8-aminoquinoline antimalarial drug (WR 242511) using oxidative electrochemical detection. 837 17

A sensitive, selective and rapid reversed-phase high-performance liquid chromatographic method was developed for the simultaneous analysis of dapsone, monoacetyldapsone and pyrimethamine in human whole blood and plasma. The procedure involved extraction of the compounds and the internal standard, monopropionyldapsone, with tert.-butylmethyl ether under alkaline conditions. A newly marketed column, Supelcosil LC-ABZ (Supelco, 15 cm x 4.6 mm I.D.), was employed. The mobile phase, consisting of acetonitrile-methanol-phosphate buffer (2:1:7, v/v/v), was delivered at a flow-rate of 1.2 ml/min, and ultraviolet absorbance was monitored at 286 nm. The limit of determination using a 150-microliters sample was 10 ng/ml (40 nM) for dapsone and pyrimethamine and 8 ng/ml (28 nM) for monoacetyldapsone. Given that only a small amount of blood is required in this method, it could now be applied in studies involving blood level monitoring and pharmacokinetics in children on Maloprim (dapsone-pyrimethamine) prophylaxis in malaria endemic areas.
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PMID:Simultaneous determination of dapsone, monoacetyldapsone and pyrimethamine in whole blood and plasma by high-performance liquid chromatography. 849 23

Free hematin can be converted to a stable polymer both chemically, by heating hematin in acid suspensions, or biologically, in the food vacuoles of malaria. A high-performance liquid chromatographic assay has been developed which can separate and quantitate both free hematin and the polymer (beta-hematin), based on the differential solubility of the two compounds. Ion-pair reverse-phase chromatography, utilizing tetramethylammonium chloride and heptane sulfonate as the ion-pair agents in the presence of 40% acetonitrile, was performed on a polymeric-resin-based column with a phenyl bonded phase. Initiating the runs at pH 2.5 led to elution only of the free hematin, and a subsequent shift to pH 12.0 converted the beta-hematin back to hematin which then eluted separately. The method was found to have a linear range of detection from 78 pmol to 20 nmol injected hematin and intra- and interday variations of 9.71 and 12.46%, respectively. The assay was used to study several basic aspects of heme polymerization in vitro, including effects of hematin and beta-hematin concentration on the rate of polymerization.
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PMID:High-performance liquid chromatographic analysis of biological and chemical heme polymerization. 867 94

A novel solid-phase extraction and a robust high-performance liquid chromatographic (HPLC) separation procedure for artesunate and alpha- and beta-dihydroartemisinin, using post-column alkali decomposition and UV detection is described. Extraction was performed with Bond-Elut Phenyl solid-phase extraction cartridges and analysis by HPLC was carried out using a Waters Symmetry C8 5-microns 150 x 3.9 mm I.D. column. The mobile phase was 50% acetonitrile in 0.1 M acetate buffer (pH 4.8) delivered at a flow-rate of 0.7 ml/min. The column eluate was mixed with 1.2 M potassium hydroxide in 90% methanol delivered at 0.3 ml/min, in a 1-ml reaction coil at 69 degrees C, to form UV-absorbing chromophores which were detected at 290 nm. The recovery of all analytes was greater than 80%. There was no significant difference in the peak-area ratio of alpha- and beta-dihydroartemisinin in plasma. Preliminary pharmacokinetic data from six adult Vietnamese patients who received 120 mg of artesunate by intravenous injection for the treatment of acute falciparum malaria are presented. Despite limited data, the mean half-life of artesunate was approximately 3.5 min while that for dihydroartemisinin was 34 min. These data confirm the relatively rapid clearance of both artesunate and its principle active metabolite, dihydroartemisinin.
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PMID:Selective high-performance liquid chromatographic determination of artesunate and alpha- and beta-dihydroartemisinin in patients with falciparum malaria. 870 40

A modification of existing HPLC assay methods is described for the measurement of dapsone and monoacetyldapsone in 50-microliter samples of plasma and whole blood. This method, in particular the use of small sample volumes dried onto filter paper strips, is applicable to multi-sample clinical and pharmacokinetic studies in children with malaria, who are often anaemic, and where sample volume must be kept to a minimum. Basified samples were extracted into 5 ml of ethyl acetate-tert.-butylmethyl ether (1:1, v/v), chromatographed on a mu BondapaK C18, 10-micron column with water-acetonitrile-glacial acetic acid (81:17.5:5, v/v) containing 2 g/l l-octanesulphonic acid as the mobile phase and detected at 274 nm.
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PMID:Measurement of physiological concentrations of dapsone and its monoacetyl metabolite: a miniaturised assay for liquid or filter paper-absorbed samples. 870 46

The interaction of a variety of quinoline antimalarial drugs as well as other quinoline derivatives with strictly monomeric ferriprotoporphyrin IX [Fe(III)PPIX] has been investigated in 40% aqueous DMSO solution. At an apparent pH of 7.5 and 25 degrees C, log K values for bonding are 5.52 +/- 0.03 (chloroquine), 5.39 +/- 0.04 (amodiaquine), 4.10 +/- 0.02 (quinine), 4.04 +/- 0.03 (9-epiquinine), and 3.90 +/- 0.08 (mefloquine). Primaquine, 8-hydroxyquinoline, 5-aminoquinoline, 6-aminoquinoline, 8-aminoquinoline, and quinoline exhibit no evidence of interaction with Fe(III)PPIX. The enthalpy and entropy changes for the interaction of quinolines with Fe(III)PPIX, as determined from the temperature dependence of the log K values, exhibit a compensation phenomenon that is suggestive of hydrophobic interaction. This is supported by the finding that the interactions of chloroquine and quinine with Fe(III)PPIX are weakened by increasing concentrations of acetonitrile. Interactions of chloroquine, quinine, and 9-epiquinine with Fe(III)PPIX are shown to remain strong at pH 5.6, the approximate pH of the food vacuole of the malaria parasite which is believed to be the locus of drug activity. Implications for the design of antimalarial drugs are briefly discussed.
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PMID:Thermodynamic factors controlling the interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX. 933 73


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