A highly dispersed multi-walled carbon nanotubes and poly(methyl orange) based electrochemical sensor for the determination of an anti-malarial drug: Amodiaquine.

A glassy carbon electrode modified with electrochemically polymerized methyl orange (PMO) and multi-walled carbon nanotubes (MWCNT) was developed. The morphologies of the fabricating materials (PMO and MWCNT) were investigated by field-emission scanning electron microscopy (FE-SEM). The designed sensor was used for the sensitive determination of amodiaquine (AQ), an anti-malaria drug. AQ was developed as an alternative to chloroquine because of its activity against chloroquine-resistant Plasmodium falciparum (P. falciparum) parasites. The modified electrode was employed to study the electrochemical oxidation of AQ using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. Under optimal experimental conditions, DPV exhibited a linear response in the concentration range from 1.0 × 10-7 to 3.5 × 10-6 mol L-1 with a limit of detection (LOD) of 8.9 × 10-8 mol L-1. Furthermore, the number of electrons and protons involved in the electrochemical study of AQ was also calculated and a plausible mechanism for the electro-oxidation of AQ was deduced. The developed sensor demonstrated analytical applicability as it was successfully employed to determine the drug AQ in pharmaceutical formulations and human urine samples.

Self-reported data: a major tool to assess compliance with anti-malarial combination therapy among children in Senegal.

BACKGROUND: Although there are many methods available for measuring compliance, there is no formal gold standard. Different techniques used to measure compliance were compared among children treated by the anti-malarial amodiaquine/sulphadoxine-pyrimethamine (AQ/SP) combination therapy, in use in Senegal between 2004 and 2006. METHODS: The study was carried out in 2004, in five health centres located in the Thies region (Senegal). Children who had AQ/SP prescribed for three and one day respectively at the health centre were recruited. The day following the theoretical last intake of AQ, venous blood, and urine samples were collected for anti-malarial drugs dosage. Caregivers and children above five years were interviewed concerning children's drug intake. RESULTS: Among the children, 64.7% adhered to 80% of the prescribed dose and only 37.7% were strict full adherent to the prescription. There was 72.7% agreement between self-reported data and blood drug dosage for amodiaquine treatment. Concerning SP, results found that blood dosages were 91.4% concordant with urine tests and 90% with self-reported data based on questionnaires. CONCLUSION: Self-reported data could provide useful quantitative information on drug intake and administration. Under strict methodological conditions this method, easy to implement, can be used to describe patients' behaviors and their use of new anti-malarial treatment. Self-reported data is a major tool for assessing compliance in resource poor countries. Blood and urine drug dosages provide qualitative results that confirm any drug intake. Urine assays for SP could be useful to obtain public health data, for example on chemoprophylaxis among pregnant women.

A simple technique for the detection of anti-malarial drug formulations and their presence in human urine.

A simple, sensitive, specific assay technique for the detection and semi-quantification of chloroquine, amodiaquine, quinine, primaquine, sulfadoxine and pyrimethamine in formulations and in human urine by using thin layer chromatography (TLC) was developed and tested in the laboratory. The method involved developing test samples spotted on TLC chromatogram by diethylamine-toluene-isopropanol (1:4:5 v/v/v) as the eluting solvent. The solvent system diethylamine-toluene-isopropanol (1:4:5 v/v/v) enabled the elution and detection of all the tested antimalarial drugs in solution and those spiked in human urine. Detection limits for chloroquine, amodiaquine, quinine and primaquine were the lowest at 0.00025 mg/ml. Sulfadoxine exhibited a detection limit of 0.0005 mg/ml whereas that of pyrimethamine was 0.001 mg/ml. The results indicate the suitability of this technique in antimalarial drug quality and bioavailability studies. It is envisaged that this technique will adequately address the role of drug absorption and excretion in the chemotherapy of malaria as well as to detect types of antimalarial drugs commonly used in the community.

High-performance liquid chromatographic method for determination of amodiaquine, chloroquine and their monodesethyl metabolites in biological samples.

A high-performance liquid chromatographic method for determination of amodiaquine (AQ), desethylamodiaquine (DAQ), chloroquine (CQ) and desethylchloroquine (DCQ) in human whole blood, plasma and urine is reported. 4-(4-Dimethylamino-1-methylbutylamino)-7-chloroquinoline was used as internal standard. The drugs and the internal standard were extracted into di-isopropyl ether as bases and then re-extracted into an acidic aqueous phase with 0.1 M phosphate buffer at pH 4.0 for AQ samples and at pH 2.5 for CQ filter paper samples. A C(18) column was used and the mobile phase consisted of methanol-phosphate buffer (0.1 M, pH 3)-perchloric acid (250: 747.5:2.5, v/v). The absorbance of the drugs was monitored at 333 nm and no endogenous compound interfered at this wavelength. The limit of quantification in whole blood, plasma and urine was 100 nM for AQ and DAQ (sample size 100 microliter) as well as for CQ and DCQ in blood samples dried on filter paper. For 1000 microliter AQ and DAQ samples, the limit of quantification was 10 nM in all three biological fluids. The within-assay and between-assay coefficients of variations were always <10% at the limits of quantification. Plasma should be preferred for the determination of AQ and DAQ since use of whole blood may be associated with stability problems.

Comparison of the urinary excretion time profile of amodiaquine in albino rabbits by fluorometric and high-performance liquid chromatographic methods.

Fluorometric and high-performance liquid chromatographic (HPLC) methods have been used to study the urinary excretion time profile of amodiaquine in albino rabbits after single oral (18.5 mg) and i.v. (9 mg) administration. There was no significant difference between the total mean values obtained for the two methods (P greater than 0.05). Although the HPLC method is more selective, one can still rely on the fluorometric method to measure urine concentrations of amodiaquine for therapeutic drug monitoring where toxicological conditions are not taken into consideration.

[Preparation of monodesethylamodiaquine from human urine]. / Préparation de monodéséthylamodiaquine à partir d'urines humaines.

60 mg of monodesethylamodiaquine, the active metabolite of amodiaquine were prepared by extraction from human urine, at pH 11-12, using ethyl acetate. The purification was carried out by medium pressure liquid chromatography. The identity and the purity of the compound were checked by thin layer chromatography, 1H nuclear magnetic resonance and mass spectrometry.

Effect of dose size on amodiaquine pharmacokinetics after oral administration.

Plasma and urine concentrations of amodiaquine (AQ) and desethylamodiaquine (AQm) have been measured after oral administration of AQ 200, 400 and 600 mg in randomised order to 6 healthy subjects. The relationships between AQ dose size and the areas under the plasma concentration vs time curves for AQ and AQm were linear. Likewise there were linear relationships between AQ dose size and the mass of both AQ and AQm excreted in the urine. These data indicate that after oral administration within this dose range AQ displays first-order pharmacokinetics.

Simultaneous determination of chloroquine, amodiaquine and their metabolites in human plasma, red blood cells, whole blood and urine by column liquid chromatography.

A column liquid chromatographic method for the simultaneous determination of chloroquine, amodiaquine and their monodesethyl metabolite in human plasma, red blood cells, whole blood and urine is described. The drugs and internal standard were extracted as bases with methylene dichloride and then re-extracted into an acid aqueous phase. Separation was obtained using a reversed-phase column and a mobile phase of phosphate buffer (pH 3.0)-acetonitrile (88:12). The absorbance of the drugs was monitored at 340 nm with a sensitivity limit of 10 pmol/ml. No endogenous compound interfered at this wavelength. The mean overall recovery from each biological fluid was greater than 75%. This method can be applied to therapeutic, pharmacokinetic and epidemiological studies. The metabolism of these two amino-4-quinolines in humans is compared.

Een onderzoek naar de aanwezigheid van amodiaquine in de urine na orale toediening / A research into the presence of amodiaquine in the urine after oral administration

Amodiaquine (Camoquin R) is an antimalarial, that belongs to the group of 4-aminoquinoline-derivates. Since 1968 it is being used in the Surinamese battle against malaria. In the Surinamese interior, ADQ (Amodiaquine) is administered as an additive to kitchen-salt, in a concentration of 0,4 per cent (WHO/Mem/l, 1960). To obtain an impression of the presence of ADQ in the urine, an attempt has been made to put up a laboratory determination. The relation between the presence of ADQ in consumed salt, and the occurrence in urine, had to be determined up to a concentration of 1/10000 M. Some inhabitants of the area around the Upper-Suriname river were examined, but ADQ was found in none of them. These negative results are probably due to a different kinetic behaviour of ADQ than that of Chloroquine