- 學位論文
以毛細管電泳分析中藥製劑中摻加抗組織胺藥物之固相萃取與分離鏡像藥物
Synthetic Anti-histamine Adulterated in Chinese Herbal Medicines by Solid-phase Extraction Capillary Electrophoresis Analysis and the Separation of their Enantiomers
摘要
在中藥製劑中摻加抗組織胺藥品之毛細管電泳分析中，本研究建立了以毛細管區帶電泳方法分析及定量五種抗組織胺藥品 diphenhydramine (DIP)、 cyproheptadine (CYP)、 chlorpheniramine (CHL)、 carbinoxamine (CAR)及 brompheniramine (BRO)，摻加於中藥製劑之研究，分析條件緩衝液為150 mM 磷酸鹽緩衝溶液 (pH 3.5) 和 17 mM α-環糊精溶液。定量實驗檢量線濃度2.0-40.0 μg/mL 我們得到很好線性關係為0.9873 至 0.9990，相對標準偏差經固相萃取後同日間和異日間結果低於10%，並以上述方法定量分析四種含抗組織胺藥品之中藥。 在中藥製劑裏摻加抗組織胺藥品之固相萃取與毛細管電泳分析中，本研究以C18固相萃取法萃取摻入中草藥製劑中之五種合成抗組織胺 DIP、 CYP、 CHL、 CAR 及 BRO，再以高效毛細管電泳評估個別之回收率。固相萃取管依序以甲醇及水活化，繼用甲醇及水 (4:1, v/v)沖出檢體，沖提液為甲醇與磷酸緩衝溶液pH 4 (79:1 v/v)。活化固相萃取條件之探討包括沖提液之pH值、不同廠牌之固相萃取管及市售中藥製劑 (辛夷散及蒼耳散)作為模擬方劑之回收率，均加以比較以建立最佳之萃取條件。 在以毛細管電泳分離抗組織胺鏡像藥物，本研究以毛細管區帶電泳方法在100 mM磷酸鹽緩衝溶液 (pH 3.0) / 6 mM β-環糊精加3 mM γ-環糊精來分離三種抗組織胺鏡像藥物。 本研究探討毛細管電泳層析之定性定量方法，同時分析五種抗組織胺類西藥成份及鏡像分離，藉以篩檢中藥成分中是否摻有抗組織胺類西藥成分。
並列摘要
A capillary zone electrophoresis (CZE) method has been developed to separate and quantitate five synthetic anti-histamines, diphenhydramine (DIP), cyproheptadine (CYP), chlorpheniramine (CHL), carbinoxamine (CAR) and brompheniramine (BRO). The electrolyte was a buffer solution containing 150 mM phosphate buffer (pH 3.5) and 17 mM α-cyclodextrin. Applied voltage was 8.0 kV and temperature was 30 °C. 2-(4-Hydroxyphenyl) ethyl ammonium chloride was used as an internal standard and detector was set at 200 nm. Calibration curves of the five synthetic anti-histamine were constructed in range 2.0-40.0 mg/mL. Their correlation coefficient ranged from 0.9873 to 0.9990. The relative standard deviations of the five synthetic anti-histamines for intraday and interday analyses were 1.98-6.37% and 7.15-9.87%. Solid-phase extraction (SPE) for the determination of synthetic anti-histamine adulterated in Chinese herbal medicines by high performance capillary electrophoresis (HPCE). A systematic evaluation and comparison of the recoveries of five synthetic anti-histamine from spiked Chinese herbal medicine (CHM) extract using C18 SPE are reported. The five synthetic anti-histamines, DIP, CYP, CHL, CAR and BRO adulterated in CHM were assayed simultaneously by HPCE. The sample solution was achieved with a C18 cartridge conditioned with methanol, water and methanol/water (4:1, v/v). The SPE column was eluted with mixed MEOH/NaH2PO4 buffer at pH 4.0 (79:1 v/v). Optimized experimental conditions including eluted pH, different brands of SPE cartridge and CHM extract concentration were also investigated. The enantiomers seperation CHL, CAR and BRO was investigated using cyclodextrin (CD)-mediated capillary zone electrophoresis. The enantiomers of drugs can be baseline separated by using 100 mM phosphate buffer (pH 3.0) and 6 mM β-cyclodextrin adding 3 mM γ-cyclodextrin. The CD type, concentration, buffer composition, organic modifier and capillary length played a role in chiral separation.