1.1. Simultaneous determination of eight antidepressants by capillary zone electrophoresis and its application in pharmaceuticals 2.Analysis of amitriptyline and its metabolite nortriptyline in plasma by field-amplified sample stacking and capillary elec

• Main Authors: huang yu hua, 黃宇樺
• Other Authors: wu shou mei
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/16913115260938694078

碩士 === 高雄醫學大學 === 藥學研究所 === 91 === 英文摘要 This study describes the establishment of capillary electrophoretic methods for the determination of eight antidepressants in available commercial formulations and the analysis of amitriptyline and nortriptyline in plasma coupling with field-amplified sample stacking. (1) Simultaneous determination of eight antidepressants by capillary zone electrophoresis and its application in pharmaceuticals A selective CZE method was established for simultaneous determination of amitriptyline, clomipramine, trimipramine, nortriptyline, protriptyline, maprotiline, doxepin and desipramine. The untreated fused-silica capillary was used (61.2 cm, effective length 50 cm, 50 mm. I.D.) for the analysis. The background buffer is Tris (0.5 M, pH 3.50) containing chiral selectors b-cyclodextrin (1.5 mM)、hydroxypropyl-b- cyclodextrin (1.5 mM) and 13 % acetonitrile. Analysis is run at the voltage of 20 kV and a detection wavelength of 200 nm. On the method validation, the calibration curves are linear over a range of 125.0-500.0 mM (r≧0.9974). The RSD and RE are all less than 3 % for the intra- and inter-day assay. All the recoveries are greater than 95 %. The limit of detection is cis-doxepine, 4 mM； protriptyline, R- or L-trimipramine, 10 mM；trans-doxepin, nortriptyline, maprotiline, amitriptyline, clomipramine, desipramine, 5 mM (S/N=5, hydrodynamic injection 3 sec). This method was feasible for the application of commercial tablets（maprotiline, amitriptyline, clomipramine） and capsules（Doxepin）. All the analytical values fall within labeled amount of 90-110 % required by the USP XXV. (2) Analysis of amitriptyline and its metabolite nortriptyline in plasma by field-amplified sample stacking and capillary electrophoresis A field-amplified sample stacking and capillary electrophoresis method is described for the determination of amitriptyline and its metabolite nortriptyline in human plasma. The untreated fused-silica capillary was used (31.2 cm, effective length 20 cm, 50 mm. I.D.) for the analysis. The background buffer is Tris (1.4 M, pH 4.50) containing b-cyclodextrin (1.0 mM) and 50 %ethylene glycol. The separation voltage is 25 kV with a detection wavelength of 200 nm. On the method validation, the calibration curves are linear over a range of 10.0-500.0 ng/mL (r≧0.9975). The RSD and RE are all less than 5 % for the intra- and inter-day assay. The relative recoveries are greater than 99 %. The limit of detection of amitriptyline and nortriptyline is 2.0 ng/mL (6.3 nM and 6.7 nM, respectively) (S/N=5, electric-driven injection 99.9 sec). One 26-yr healthy volunteer (male, 70 kg) took 125.0 mg of amitriptyline tablets. After dosing, the blood samples were drawn at 26-, 54-, and 78-hr intervals. The plasma was separated, extracted and analyzed. The levels of amitriptyline and its metabolite, nortriptyline were determinated and met closely the calculated data from pharmacokinetics of amitriptyline. A simple and sensitive CE method was applied for therapeutic drug monitoring. Comparisons between these two methods, the LODs of amitriptyline are 5 mM and 6.3 nM, respectively. The sensitivity can be raised about thousand folds by field-amplified sample stacking technique.