•A bioanalytical method for lumefantrine and its main metabolite desbutyl-lumefantrine was developed.•Two isotopically labeled internal standards give robust quantification.•Sensitivite and short ...analysis times is applicable to large volume studies.•The method was successfully applied for clinical samples.
A sensitive liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed for quantification of lumefantrine (LUM) and its metabolite desbutyl-lumefantrine (DBL) in human plasma. Sample preparation was done by protein precipitation using acetonitrile containing deuterated lumefantrine (LUM-d18) and desbutyl-lumefantrine (DBL-d9) as internal standards. Total chromatography time was 2.2min using an Hypersil Gold C18 column (20×2.1mm, 1.9μm), with a gradient using 0.5% formic acid in water (mobile phase A) and 0.5% formic acid in methanol (mobile phase B) at a flow rate of 0.5mL/min. The mass spectrometric quantification was performed in positive electro spray ionization (ESI+) mode using selected reaction monitoring (SRM). Measuring range was 21–529ng/mL for LUM and 1.9–47ng/mL for DBL in plasma. Inter- and intra-assay precision was within 10% coefficient of variation (CV) for all levels of both LUM and DBL. Accuracy was within ±10% for all levels of both LUM and DBL. This method requires 100μL plasma volume and its short retention times allow a high throughput. Samples were stable for a week at +5°C, and up to six months −20°C. The method was successfully applied for plasma LUM and DBL determination in children under 5 years of age with uncomplicated malaria, up to 28 days after a standard 3-day treatment with artemether-lumefantrine.
A reversed-phase high performance liquid chromatographic method was developed and validated for the quantitative determination of amodiaquine (AQ) and its metabolite desethylamodiaquine (DAQ) in ...whole blood collected on filter paper. The structure analogue 4-(4-dimethylamino-1-methylbutylamino)-7-chloroquinoline was used as internal standard. Upon collection, blood was added to 10% phosphoric acid in a 1:1 ratio and then spotted onto filter paper. The samples were alkalinized (pH
≈
9.2) with potassium hydroxide at the time of assay and the compounds were extracted together with internal standard into di-isopropyl ether and then re-extracted into an aqueous phase with 0.1
M phosphate buffer at pH 4. The chromatographic analysis was performed using an Agilent Technologies ChemStation LC System. The absorbance of the compounds was monitored at 333
nm. Mean extraction recoveries of AQ and DAQ were 49 and 48%, respectively. Intra-day and inter-day coefficients of variation were <10.5%. The limit of quantification was 50
nM for both compounds (sample size 100
μl). Both AQ and DAQ that were previously reported to be unstable have been stored on filter paper for at least 19 weeks. The method was applied on samples from healthy volunteers.
A quantitative reverse-phase HPLC method with UV detection, for lumefantrine (LF) and desbutyllumefantrine (DLF) in whole blood spotted on filter paper was developed. The analytes were stabilized on ...filter paper by treatment of blood with phosphoric acid (1.6
mol/L). Halofantrine was used as internal standard and the analytes were extracted from filter paper using methanol. The methanolic extract was extracted with di-isopropylether after addition of acidic phosphate buffer (pH 2). Chromatographic separation was carried out on a Zorbax Eclipse XDB-phenyl column (4.6
mm
×
150
mm, particle size 5
μm) at a flow rate of 1
mL/min using a mobile phase of acetonitrile–ammonium acetate buffer (0.1
M ammonium acetate and 0.01
M acetic acid, pH 6.5) (10:90). The absorbance of the compounds was monitored at 335
nm. The average extraction recovery from filter paper ranged between 45–51% for LF and 25–33% for DLF for a concentration range between 300 and 3000
nM. Inter- and intra-assay coefficients of variation for LF and DLF were ≤9.2. Limits of quantification for LF and DLF were 300
nM. The method has been applied in malaria patients. In conclusion, a simple procedure for blood sampling and quantitative measurement of lumefantrine and desbutyllumefantrine suitable for field studies in resource-limited laboratories was developed.
Résumé
Des sept espèces d’anophèles identifiées dans la région de Lwiro-Katana en 1967, quatre ont été régulièrement récoltées au stade larvaire au cours des neuf enquêtes effectuées durant ces ...cinquante dernières années. Par ordre croissant de fréquences, il s’agit de:
Anopheles funestus
,
An. gambiae sl
,
An. demeilloni
et
An. marshallii
. Les larves de ces espèces se développent presque toutes dans des gîtes à eau claire, fraîche, ensoleillée et avec ou non un léger couvert végétal. Ces gîtes larvaires sont très généralement créés dans la région par les activités humaines. Les courbes d’évolution des 3 espèces anophéliennes les plus importantes dans l’épidémiologie du paludisme présentes à Lwiro-Katana montrent une très nette tendance à l’augmentation des captures d’
An. gambiae sl
au fil du temps, une présence relativement constante d’
An. funestus
, et une régression, amorcée dès les années 1980 jusqu’à sa disparition temporaire en 2014 de l’espèce
An. marshallii
. La présence des autres espèces d’
Anopheles
a été variable et dépend autant de perturbations environnementales que de facteurs climatiques saisonniers. Toutes ces espèces présentent un intérêt scientifique et enrichissent la biodiversité d’une région. Certaines espèces anophéliennes ont également un intérêt sanitaire, notamment celles intervenant dans la transmission du paludisme (
An. funestus
et
An. gambiae
). Une meilleure connaissance de l’évolution bio-écologique de ces espèces participe à l’amélioration de la surveillance des vecteurs et permettra d’optimiser la lutte antivectorielle.
Human exposure to veterinary drugs like fluoroquinolones occurs due to the presence of their residues in foods from animal sources in varying concentrations. The existence of antibiotic residues in ...foodstuffs can pose great public health problems to consumers. This study aimed to assess enrofloxacin use patterns and assess residue levels of enrofloxacin/ciprofloxacin in breast muscle and liver tissues of broiler chickens sold for consumption in Kampala capital city.
This was a cross-sectional study that involved both field survey and laboratory-based methods. The field study involved the use of qualitative and semi-quantitative data collection tools to interview 34 broiler farmers and 10 veterinary drugs vendors. For the determination of enrofloxacin/ciprofloxacin levels, 68 chicken breast and liver tissue samples were collected from main markets in Kampala over one month and analyzed using HPLC-UV.
Enrofloxacin was the most used antibiotic (100%) for the management of poultry diseases, majorly respiratory diseases (100%), salmonella infections (40%), and disease prevention (60%). Over 76% of the farmers knew the meat withdrawal time (WDT) for enrofloxacin, but none of them adhered to this. Over 70% of the farmers reported that the veterinary drugs vendors were not providing meat WDT information. Enrofloxacin/ciprofloxacin residues were identified in 35.3% (12/34) of the muscle and 38.2% (13/34) of the liver tissues analyzed. Of those muscle and liver tissue samples that tested positive, 25% (3/12) and 38.5% (5/13) respectively had drug concentrations higher than the recommended Maximum Residue Limits. The overall mean enrofloxacin/ciprofloxacin concentration in the chicken muscle and liver tissues was 83.6 (±34.5) µg/kg and 171.5 (±75.9) µg/kg.
This observed presence of enrofloxacin/ciprofloxacin levels above safety requirements is attributable to inadequate medicines use information provided by veterinary drugs vendors to farmers and also to the non-compliance of some farmers to meat WDT due to the economic implications.
The population of the Ugandan capital city of Kampala has dramatically increased since the political turmoil of the 1970s and with it a considerable rise in industrialisation. Few manufacturing ...plants, however, have pretreatment installations in place for their polluted effluent prior to discharge into the surrounding ecosystems. Kampala's main drainage system is the Nakivubo channel which empties directly into the neighbouring Lake Victoria, the second largest inland freshwater lake in the world. Increased urban effluent load coupled with reclamation for crop farming have considerably reduced the effectiveness of the wetland to filter out major pollutants, in particular heavy metals. Using atomic absorption spectrophotometry, this study showed that the efficiency in sieving out zinc (Zn), copper (Cu), cadmium (Cd) and lead (Pb) has shrunk from 89.7 - 98.3% in December 2006 to 79.4 - 92.1% in December 2008, over a period of three consecutive years. This is indicative of the growing ineffectiveness of the wetland to absorb heavy metals. Levels of the same metals in the lake water some two kilometres away from the mouth of the wetland have correspondingly increased from 23 - 31% to 35 - 47% in the same period. This poses a serious threat to the quality of the fish and to the over two million urban population that directly depend on the lake water for domestic and industrial use. The remedy lies in the relevant authorities to enforce pretreatment at each factory site, increased factory management sensitisation on environmental concerns and more stringent measures against wetland encroachment. PUBLICATION ABSTRACT
The available data have shown that acid-leached clays had sites for adsorption of impurities in oils. Data obtained on residual impurities in cotton and sunflower-seed oils bleached with the same ...clay materials produced linear Langmuir and Freundlich isotherms. The increase in constant, k with increase in both temperature of thermal activation and concentration of acid used to leach the clay, suggests that bleaching efficiency increased. The value of n decreased with increase in temperature of activation and concentration of acid used to leach the clay suggesting that bleaching capacity increased. The mineral compositions of the clays influenced their surface, structural and bleaching properties.
The Langmuir isotherms of 1-aminobutane in isohexane slurries showed increase in clay acidity with increase in concentration of mineral acid used to leach the clay as well as the temperature at which ...the clay was thermally activated prior to experimentation involving adsorption of 1-aminobutane. The values of acidity for Central Uganda were low ranging from 0.07 mol/g to 0.32 mol/g yet those for clays from Eastern Uganda were high ranging from 0.1 mol/g to 1.85 mol/g. Based on acidity, pH, elemental and mineral compositions, the clays from Central Uganda were found to be kaolinites or halloysites, yet Eastern Uganda clays were resolved to contain nontronite and kaolinite.
Co-administration of artemether/lumefantrine with antiretroviral therapy has potential for pharmacokinetic drug interactions. We investigated drug-drug interactions between artemether/lumefantrine ...and efavirenz or nevirapine.
We performed a cross-over study in which HIV-infected adults received standard six-dose artemether/lumefantrine 80/480 mg before and at efavirenz or nevirapine steady state. Artemether, dihydroartemisinin, lumefantrine, efavirenz and nevirapine plasma concentrations were measured and compared.
Efavirenz significantly reduced artemether maximum concentration (C(max)) and plasma AUC (median 29 versus 12 ng/mL, P < 0.01, and 119 versus 25 ng · h/mL, P < 0.01), dihydroartemisinin C(max) and AUC (median 120 versus 26 ng/mL, P < 0.01, and 341 versus 84 ng · h/mL, P < 0.01), and lumefantrine C(max) and AUC (median 8737 versus 6331 ng/mL, P = 0.03, and 280 370 versus 124 381 ng · h/mL, P < 0.01). Nevirapine significantly reduced artemether C(max) and AUC (median 28 versus 11 ng/mL, P < 0.01, and 123 versus 34 ng · h/mL, P < 0.01) and dihydroartemisinin C(max) and AUC (median 107 versus 59 ng/mL, P < 0.01, and 364 versus 228 ng · h/mL, P < 0.01). Lumefantrine C(max) and AUC were non-significantly reduced by nevirapine. Artemether/lumefantrine reduced nevirapine C(max) and AUC (median 8620 versus 4958 ng/mL, P < 0.01, and 66 329 versus 35 728 ng · h/mL, P < 0.01), but did not affect efavirenz exposure.
Co-administration of artemether/lumefantrine with efavirenz or nevirapine resulted in a reduction in artemether, dihydroartemisinin, lumefantrine and nevirapine exposure. These drug interactions may increase the risk of malaria treatment failure and development of resistance to artemether/lumefantrine and nevirapine. Clinical data from population pharmacokinetic and pharmacodynamic trials evaluating the impact of these drug interactions are urgently needed.
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