| Summary: | 博士 === 高雄醫學大學 === 藥學研究所博士班 === 94 === Abstract
Amino compounds are widely found in biological and pharmaceutical samples. Chromophoric compounds such as fluoxetine, fluvoxamine, sertraline and trazodone can be directly analyzed at trace levels by absorption spectrophotometry. However, many amino compounds including amantadine and memantine are lack of chromophore in structure; therefore, they can not be directly analyzed at trace levels by absorption spectrophotometry. Using chemical derivatization, a responsive label such as a fluorophore, chromophore or electrophore can be incorporated into a target analyte for sensitive analysis. The search for fluorescent reagents for analytical derivatization in chromatography was made in this study, we found a simple chemical, (2-naphthoxy)acetyl chloride, with potential fluorophore / chromophore characteristics for highly sensitive detection of the analytes with an amino function. The reagent has an auxochrome (a substituted alkoxy moiety) attached to the fluorophoric/chromophoric naphthalene system, resulting in favorable spectrophotometric properties. Application of the reagent to the trace analysis amantadine and memantine was demonstrated. The method is based on the derivatization of amantadine and memantine extracted from alkalified samples with (2-naphthoxy)acetyl chloride at mild conditions. The resulting derivatives were analyzed by isocratic HPLC with a fluorimetric detector (?鈃x, 227 nm; ?鈃m, 348 nm). The main results of this study are summarized as follows:
1. A simple and sensitive method is described for the analysis of amantadine and memantine in human plasma. The linear range for the determination of amantadine or memantine spiked in plasma (0.3 mL) was 0.3-3.0 nmol with a detection limit of about 1.2 pmol (S/N = 3; injected sample 20 ?尳). The precision (relative standard deviation) and accuracy (relative error) of the method for intraday analyses of amantadine and memantine were all below 3.5 %. Therefore, the method could be applicable for the pharmacokinetic study of amantadine and memantine in plasma.
2. A simple and sensitive method is described for the analysis of amantadine and memantine in human urine. The linear range for the determination of amantadine or memantine spiked in urine (1.0 mL) was 1.0 – 10. 0 nmol. The detection limit (S/N = 3) of amantadine or memantine was 0.2 nmol spiked in urine, equivalent to about 1.6 pmol of amantadine or memantine injected (20 ?尳). The precision (relative standard deviation) and accuracy (relative error) of the method for intra- and inter-day analyses of amantadine and memantine were all below 2.6 %.
3. Only amantadine preparation is available on local market, and application of the method to the analysis of amantadine in formulation was studied. Quantification of amantadine in tablets or capsules is capable in the linear range of 2.0 – 50.0 ?嵱. The precision (relative standard deviation) and accuracy (relative error) of the method for intra- and inter-day analyses of amantadine were all below 3.5 %. The method was demonstrated to the analysis of amantadine in capsules and tablets.
4. Fluoxetine, fluvoxamine, sertraline and trazodone are new antidepressants enhancing serotoninergic neurotransmission through potent and selective inhibition of serotonin reuptake. They have chromophores in their structures and can be directly analyzed at trace levels by absorption spectrophotomery. A high-performance liquid chromatographic method with ultraviolet detection (HPLC-UV) was developed for the simultaneous separation and quantification of fluoxetine, fluvoxamine, sertraline and trazodone. Quantification of fluoxetine in capsules, fluvoxamine or sertraline in tablets is capable in the linear range of 10.0 – 400.0 ?嵱. The precision (relative standard deviation) and accuracy (relative error) of the method for intra- and inter-day analyses of fluoxetine, fluvoxamine, sertraline and trazodone were all below 3.7 %.
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