Systematic Method Developlvient For The Determination Of Artemether And Its Met Abolite Dihydroartemisinin
| dc.contributor.author | Chin, Lee Kean | |
| dc.date.accessioned | 2016-10-14T01:48:27Z | |
| dc.date.available | 2016-10-14T01:48:27Z | |
| dc.date.issued | 1996-03 | |
| dc.description.abstract | Two assay methods were developed for the plasma measurement of artemether. The first one is based on a liquid-liquid extraction of the drug by isooctane with a high performance liquid chromatography coupled with ultra violet (HPLC-UV) detection at 211 nm. However the lowest detectable limit with confidence for artemisinin and artemether is 20 and 60 ng on column. It is realised that this method has a relatively low sensitivity but a reasonable accuracy above the limits of detection. It should suffice for assessing therapeutic drug monitoring but not suitable for routine analysis of blood samples in pharmacokinetic studies. For measurement of drug concentrations below the limits of detection by the HPLC -UV method, a selective and reproducible high peri()(Jl1HnCe liquid clllolllatography coupled with an ciectrochelllical detection (HPLC-ECD) assay for the simultaneous quantitative determination of the antimalarial compounds artemether, dihydroaI1emisinin and artemisinin, as internal standard is described After extraction from plasma, artemether and dihydroartemisinin were analysed using a Lichrocart/Lichrosphere 100 eN stainless steel column and a mobile phase of acetonitrile 0.05M acetic acid (15 85 v/v) adjusted to pH 5.0, and electrochemical detection in the reductive mode. The mean recovery of artemether and dihydroartemisinin over a concentration range of 30-120 ng/ml was 99.62% and 99.39% respectively The within-day coefficients of variati<n were 0.89-7.01 % for artemcther and 3.45-8.11 % for dihydroartemisinin. The day-to-day coetllcients of variation were 2.06-8.43% and 6.33-8.22% respectively. The minimum detectable concentration in plasma was 5 ng/mg for both compounds. The method was found to be suitable for lise in clinical pharmacological studies. The maximum blood concentration (Cmax) of 422.5 ng/ml of a preliminary pharmacokinetic profile after a single administration of artemether to a healthy Malaysian volunteer was reached 1.75 hOllrs following drug administration, and the area under curve (AUC) was 654 ng/ml. The plasma clearance (CI), apparent volume of distribution (Vd) and elimination halflife (tll2) were 3060 mllmin, 282L and 1.06 hour respectively. Dihydroartemisinin reached Cmax of3868 ng/ml, 1.75 hr upon administration oC artemether with an area under curve (AUC) of 604 nghr/mL CI, V d and t 112 values for this metabolite were 3310 IImin, 296 Land l. 03 hr respectively. | en_US |
| dc.identifier.uri | http://hdl.handle.net/123456789/2745 | |
| dc.subject | Two assay methods were developed for | en_US |
| dc.subject | the plasma measurement of artemether | en_US |
| dc.title | Systematic Method Developlvient For The Determination Of Artemether And Its Met Abolite Dihydroartemisinin | en_US |
| dc.type | Thesis | en_US |
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