Study And Application Of Some Common Toxic Alkaloids By High Performance Capillary Electrophoresis Coupled To Time-of-flight Mass Spectrometry Techniques

Alkaloids, a group of important bioactive compounds, are mainly from many kinds of pharmaceutical plants. But many alkaloids have some toxicity. To develop a reliable method for the identification and qualification of these toxic alkaloids is very important for the fields of forensic as well as clinical and pharmaceutics.High-performance capillary electrophoresis (HPCE) is both widely applied and actively studied in the field of separation science. In the fields of forensic toxin analysis, HPCE represents a new detective tool which has been proved to be suitable for many kinds of toxicological drugs in preparations and in complex matrices. HPCE has some obvious advantages such as a high efficiency, little sample consumption, small solvent consumption and complementary separation mechanisms to existing chromatographic methods.Mass detection, as one of the detective ways, is widely applied in many fields because it have high detective sensitivity, powerful qualitative capability and can provide structural information of tested samples. The mass filter of (time of flight mass spectrometer, TOF/MS) is a drift tube. The separation principle of TOF/MS is that the ions enter the non-field drift tube from ion source and then reach to the ion receiver at a constant speed. All ions can be separated by the values of m/z. TOF/MS has more advantages such as wide range of molecular weight, fast scanning speed and simple apparatus structures. HPCE-MS has developed a very important analytical tool which has much distinct superiority such as high separation efficiency, broad sampling adaptability and providing structural information of samples,In this thesis, CE-MS method was studied in term of application in six common toxic alkaloids. The main contents are summarized as follows1. A novel capillary zone electrophoresis separation coupled to electro spray ionization time-of-flight mass spectrometry (CE-ESI-TOF-MS) method was developed and validated for the simultaneous analysis of six toxic alkaloids:brucine, strychnine, sulfate atropine, anisodamine hydrobromide, scopolamine hydrobromide and anisodine hydrobromide in human plasma and urine. A sample clean-up pretreatment by solid-phase-extraction (SPE) using Oasis MCX cartridges (1mL,30mg; Waters, USA) was used. Under the optimal condition, all samples can be separated and this CE-MS method was proved to be sensitive, fast and simple. The limit of quantification of this method is0.5ng/mL.2. A CE-MS method of detecting strychnine and brucine in rat plasma and tissue samples was developed and validated. The results showed that this CE-MS method accords with criterion of bioanalysis.3. To investigate pharmacokinetic properties of strychnine and brucine in rats. Strychnine and brucine were best fitted to two compartment model after oral administration at the dose of4mg/kg and10mg/kg by using (Drug and Statistics, DAS) pharmacokinetic calculation program. Rat tissues concentration was determined using CE-MS method. A sample clean-up pretreatment by solid-phase-extraction (SPE) using Oasis MCX cartridges (1mL,30mg; Waters, USA) was used. This method was fast, simple and can be applied for the studies of pharmacokinetics and tissue distribution.