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- Blessborn, Daniel, et al.
(författare)
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Assay for screening self medication of common antimalarial drugs using the dried blood spot technique
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Annan publikation (populärvet., debatt m.m.)abstract
- The aim of the developed assay is to determine drug use and self medication in areas where achange in treatment policy has taken place. The assay will be a complement to interviewing patients and will increase reliability of the survey. Several of the drugs included in this screening assay have long half-lifes e.g. chloroquine, sulfadoxine, mefloquine, andlumefantrine and are detectable at least 7 days after administration. The sample collection is very simple, using 100 μl capillary whole blood applied onto Whatman 31 ET Chr filter paper.The drugs are extracted from the dried blood spot with two different extraction methods (due to the big differences in physico-chemical properties). Solid phase extraction is used as sample clean-up and separation is performed with gradient-LC with MS ion-trap detection. Detection limits (S/N > 5:1) at 50 ng/ml or better were achieved for all drugs except lumefantrine (200 ng/ml)
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| 3. |
- Blessborn, Daniel, et al.
(författare)
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Determination of Lumefantrine after Capillary Sampling onto Sampling Paper
- 2007
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Ingår i: The Royal Society of Tropical Medicine and Hygiene. - London.
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Konferensbidrag (refereegranskat)abstract
- The antimalarial lumefantrine was first synthesised and registered in China and is now commercially available as a coformulated product together with artemether (Coartem®/Riamet®). This combination is well tolerated and has proven highly efficacious for treatment of uncomplicated falciparum malaria. Lumefantrine is highly lipophilic with an extensive protein binding (99.9%). The day 7 plasma lumefantrine level has been shown to be an important determinant of treatment efficacy. To date no method has been published for the determination of lumefantrine after capillary sampling onto filter paper for field use. The aim of this work was to develop a method with adequate sensitivity for quantification of lumefantrine in capillary blood sampled onto filter paper. The method has been validated according to the current FDA guideline for bioanalytical method validation. Method: Whatman 31 ET Chr filter paper was pre-treated with an organic acid before sampling capillary blood to enable a high recovery of lumefantrine. Lumefantrine was extracted from the filter paper, then further purified using solid phase extraction and finally quantified with HPLC. Results: The between day variation is below 10 % over the range 0.4 to 25 µmol/l. The lower limit of quantification is 0.25 µmol/l in 100 µl capillary blood. No decrease in Lumefantrine concentration in dried blood spot is seen after 3 months at 37o C. The field sampling for lumefantrine assay with pre-treated Whatman 31 ET Chr has been tested in Tanzania with good results. Discussion: The field sampling for lumefantrine concentration assay with pre-treated Whatman 31 ET Chr has been evaluated and proven to be a valid method for field studies. The day 7 level after treatment can lumefantrine be accurately estimated in capillary blood to follow up compliance and efficacy. Validation data will be presented.
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| 4. |
- Blessborn, Daniel, et al.
(författare)
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Determination of pyronaridine in whole blood by automated solid-phase extraction and high-performance liquid chromatography
- 2003
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Ingår i: Therapeutic Drug Monitoring. - : Ovid Technologies (Wolters Kluwer Health). - 0163-4356 .- 1536-3694. ; 25:3, s. 264-270
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Tidskriftsartikel (refereegranskat)abstract
- A new extraction procedure for the analysis of pyronaridine in whole blood is presented. A weak cation exchanger with a carboxylic acid (CBA) sorbent was found to be a suitable solid phase sorbent for the extraction of pyronaridine. High-performance liquid chromatography with UV detection at 278 nm and an electrochemical detector at +0.75 V is used. The electrochemical detector gives higher selectivity than the UV detector. The separation was performed using a C18 reversed phase column with mobile phase of acetonitrile-phosphate buffer (0.01 mol/L, pH 2.5)- sodium perchlorate (1.0 mol/L; 22:77:1, v/v/v). The within-day RSDs were below 5% at all concentration levels between 75 nmol/L and 1500 nmol/L, and the between-day RSDs were below 14% at all concentration levels. The limit of quantification was about 50 nmol/L in 1000 microL whole blood with an RSD of 20% or less on a day-to-day basis. The stability of pyronaridine is increased if the pH is less than 3 in water solutions. In whole blood, the concentration decreases by about 10% for each freeze-thaw cycle performed. At room temperature (about 22 degrees C), pyronaridine concentration in whole blood decreases by about 10% within 12 to 24 hours.
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| 5. |
- Blessborn, Daniel, et al.
(författare)
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Development and validation of an automated solid-phase extraction and liquid chromatographic method for determination of lumefantrine in capillary blood on sampling paper
- 2007
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Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier BV. - 0731-7085 .- 1873-264X. ; 45:2, s. 282-287
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Tidskriftsartikel (refereegranskat)abstract
- A bioanalytical method for the determination of lumefantrine in 100 μl blood applied onto sampling paper, by solid-phase extraction and liquid chromatography, has been developed and validated. Whatman 31 ET Chr sampling paper was pre-treated with 0.75 M tartaric acid before sampling capillary blood to enable a high recovery of lumefantrine. Lumefantrine was extracted from the sampling paper, then further purified using solid-phase extraction and finally quantified with HPLC. The between-day variation was below 10% over the range 0.4-25 μM. The lower limit of quantification was 0.25 μM in 100 μl capillary blood. No decrease in lumefantrine concentration in dried blood spot is seen after 4 months storage at 22 °C. The method was also evaluated in field samples from patients in Tanzania after treatment with lumefantrine/artemether. Lumefantrine could be estimated accurately enough to assess bioavailability and treatment compliance on day 7 (i.e. 4 days after the last dose) after a standard regimen with the lumefantrine/artemether combination.
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| 6. |
- Friberg Hietala, Sofia, 1973, et al.
(författare)
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Population pharmacokinetics and pharmacodynamics of artemether and lumefantrine during combination treatment in children with uncomplicated falciparum malaria in Tanzania
- 2010
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Ingår i: Antimicrobial agents and chemotherapy. - 1098-6596. ; 54:11, s. 4780-4788
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Tidskriftsartikel (refereegranskat)abstract
- The combination of artemether and lumefantrine is currently the first line treatment of uncomplicated falciparum malaria in mainland Tanzania. While the exposure to lumefantrine has been associated with the probability of adequate clinical and parasitological cure, increasing exposure to artemether and the active metabolite dihydroartemisinin has been shown to decrease the parasite clearance time. The aim of this analysis was to describe the pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin and lumefantrine in African children with uncomplicated malaria. In addition to drug concentrations and parasitemias from 50 Tanzanian children with falciparum malaria, peripheral parasite densities from 11 asymptomatic children were included in the model of the parasite dynamics. The population pharmacokinetics and pharmacodynamics of artemether dihydroartemisinin and lumefantrine were modeled in NONMEM. The distribution of artemether was described by a two-compartment model with a rapid absorption and elimination through metabolism to dihydroartemisinin. Dihydroartemisinin concentrations were adequately illustrated by a one compartment model. The pharmacokinetics of artemether was time dependent with typical oral clearance increasing from 2.6 L/h/kg on day one to 10 L/h/kg on day three. The pharmacokinetics of lumefantrine was sufficiently described by a one-compartment model with an absorption lag time. The typical value of CL/F was estimated to 77 mL/h/kg. The proposed semi-mechanistic model of parasite dynamics, while a rough approximation of the complex interplay between malaria parasite and the human host, adequately described the early effect of ARM and DHA concentrations on the parasite density in malaria patients. However the poor precision in some parameters illustrates the need for further data to support and refine this model. The patient study is registered at www.Clinical.Trials.gov, (NCT00336375).
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