許多已上市藥品具有鏡像異構物，但臨床使用上卻是外消旋化物(racemate)，也就是以兩個鏡像異構物50:50比例混合之混合物。而這兩個化學結構相似的鏡像異構物卻常有著不同的藥效與藥動性質。一般用於消旋化物的藥物定量方法，因為無法分析出鏡像異構物的差異，可能造成在探討鏡像異構物的藥物動態訊息上，有嚴重的影響及損失。Amisulpride屬於非典型的抗精神病藥物，且具有兩個鏡像異構物。而相關研究顯示S(-)amisulpride較R(+)amisulpride具有主要的藥理活性。然而在探討amisulpride鏡像異構物方面，由於相關分析方法十分缺乏，且大部分的amisulpride的定量方法主要是運用在藥物製劑上，很少有針對生物檢體上的應用，故影響到有關amisulpride鏡像異構物藥物動力學之探討。
因此本研究目的在於開發並確效兼具靈敏、對掌性的及可定量amisulpride鏡像異構物於小體積之大白鼠血漿中濃度的高效液相層析法與毛細管電泳法 ; 並將所開發之方法應用在偵測amisulpride
鏡像異構物在大白鼠體內之濃度。
實驗結果已成功的開發了三種amisulpride之分析方法，分別是運用螢光偵測的非對掌性高效液相層析法、使用經修β-cyclodextrin衍生物作為對掌試劑與搭配螢光偵測之對掌性高效液相層析法及同樣使用經修飾β-cyclodextrin衍生物作為對掌試劑與搭配光電二極體偵測器偵測的毛細管電泳法。其中，非對掌性高效液相層析法與對掌性毛細管電泳法運用在小體積之大白鼠血漿中amisulpride濃度之偵測經過完整的確效評估。此外，並以具對掌性毛細管電泳法運用來偵測大白鼠體內amisulpride鏡像異構物之濃度。自靜脈注射給予大白鼠amisulpride的實驗中顯示，amisulpride鏡像異構物在大白鼠體內具有類似的濃度及藥品動態。而在離體肝臟灌流amisulpride的實驗中顯示，amisulpride鏡像異構物在大白鼠膽汁中具有立體選擇性的差異。其中S(-)amisulpride的濃度大於 R(+)amisulpride且具有統計學上之差異，這也暗示了藥物運輸子（例如P-gp）之於amisulpride或許具有立體選擇性之差異。
整體而言，本研究成功的開發了三個可以偵測於小體積之大白鼠血漿中amisulpride及其鏡像異構物的高效液相層析法與毛細管電泳法。此外並成功的運用在偵測大白鼠體內amisulpride鏡像異構物的藥品濃度，此外並發現amisulpride在膽汁中具有主動且立體選擇性的排除作用。然而，關於amisulpride鏡像異構物的藥動機制仍需做近ㄧ步研究才可以釐清。

Introduction:Many drugs are marketed as racemic mixtures, although the individual enantiomers frequently differ in both their pharmacodynamic and pharmacokinetic profiles. The importance of stereochemistry and hence the need for enantioselective analytical methods has long been recognized especially in pharmacokinetic studies. Amisulpride((±)-4-amino- N-[(1-ethyl- 2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-methoxybenzamide) is an atypical antipsychotic drug that has two enantiomers. In vitro binding studies show that S(-)amisulpride owns the major pharmacologic activities than R(+)amisulpride. However, only a few studies have investigated the chiral separation of amisulpride. Most of the analytical methods of amisulpride are for the application in pharmaceuticals, and not for the quantification of amisulpride enantiomers in biological fluids. For these reasons, pharmacokinetic studies of enantiomers of amisulpride are limited.

Purpose: The aim of this study was to develop and validate sensitive and enantioselective high-performance liquid chromatographic (HPLC) method and capillary electrophoretic (CE) method for the analysis of amisulpride in small volumes of rat plasma, and to apply the methods to characterize the kinetics of amisulpride enantionmers in rats.

Results: Three new sensitive analytical methods for amisulpride were developed, including an achiral HPLC method with fluorescence detection, a chiral HPLC method with fluorescence detection using modified β-cyclodextrin derivative as the chiral selector, and a chiral CE method with photo-diarry detection using modified β-cyclodextrin derivative as the chiral selector. The achiral HPLC method and the chiral CE method were validated for the determination of amisulpride in small volumes of rat plasma. The chiral CE method was applied to pharmacokinetic studies of amisulpride in rats. It was shown that the disposition kinetics of amisulpride enatiomers following bolus injection of amisulpride to rats were similar. However, active biliary secretion of amisulpride was found in the isolated perfused rat liver. Furthermore, as S(-)amisulpride has higher biliary concentration than R(+)amisulpride, the secretion appeared to be enantioselective.

Conclusion. In summary, three new sensitive HPLC and CE methods were developed and validated for the determination of amisulpride and its enantiomers in biological fluids. The CE method was applied successfully to characterize the disposition kinetics and the active and enantioselective biliary secretion of enatiomers of amisulpride in rats.

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