Application of Caplillary Electrophoresis to Separate Enantiomeric Pharmaceutical Drugs

碩士 === 國立中央大學 === 化學研究所 === 96 ===  Recently, pharmaceutical residues are an emerging concern in environ- mental research. Large quantities of pharmaceuticals are continuously produced, consumed, and excreted into the environment, but the subsequent environmental occurrence, fate, and effects of the...

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Bibliographic Details
Main Authors: Chia-Tien Li, 李佳恬
Other Authors: Wang-Hsien Ding
Format: Others
Language:zh-TW
Published: 2008
Online Access:http://ndltd.ncl.edu.tw/handle/82001307993662677036
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Summary:碩士 === 國立中央大學 === 化學研究所 === 96 ===  Recently, pharmaceutical residues are an emerging concern in environ- mental research. Large quantities of pharmaceuticals are continuously produced, consumed, and excreted into the environment, but the subsequent environmental occurrence, fate, and effects of these residues are not well understood, especially the work on understanding the chiral pharmaceutical residues in our environ- ment. Chirality should be concerned due to their possible different biological and/or toxicological effects from one another and from the racemate.  Ibuprofen and ketoprofen were used as the model chiral compounds in our study, which are the widely used nonsteroidal anti-inflammatory drugs (NSAIDs) in Taiwan. These two residues have been demonstrated as emerging contami-nants which can cause side effects in organisms and has raised increasing concern about their impact on wildlife and human health.  A method of capillary electrophoresis (CE) with UV detector was developed to determine the ibuprofen and ketoprofen enantiomers in over-the-counter (OTC) drugs sold in Taiwan and environmental water samples. For OTC drugs, the samples were directly dissolved in methanol and filtered before CE analysis. For environmental water samples, they were extracted by solid-phase extraction (SPE). The analytes were then separated and quantitated by CE with 20 mM sodium acetate buffer, consisting of 10 mM CM-β-CD and 30 mM TM-β-CD used as chiral selectors in dual cyclodextrin system, at pH 5.0. Baseline separation of two pair of chiral compounds confirmed the specificity of the method. Less than 18% of quantitation errors comparison with the contents displaying on the drug-packings and our results for selected OTC-drugs proved the accuracy of the method. The limit of quantitation (LOQ) was less than 1.0 µg/L for each enantiomer in 200 mL of environmental water sample. The spiked recoveries of four enantiomers were above 70 % while RSD was below 7.5 %. However, four enantiomers were not detected in five selected environmental water samples.  Furthermore, a fluorescent derivatization procedure and CE-laser-induced fluorescence (LIF) detection methods were developed to enhance the sensitivity and selectivity. However, due to the unstability of the derivatives and the low tolerance to matrix effects, the preliminary results show that CE-LIF was not suitable for this kind of studies.