| A high Performance Liquid Chromatography methed was used to determine the content of Betahistine Hydrochloride, Betahistine Hydrochloride Tablets and Betahistine Hydrochloride Injection in this paper, and the methodological study of each was carried out. A Headspace Gas Chromatography was developed for the determination of organic solvent residues in Betahistine Hydrochloride. A High Performance Liquid Chromatography tandem Mass Spectrometry method was developed for the analisis of the related substances in Betahistine Hydrochloride. After separation and purification, confirming chemical structure of the purification, and the Ultra-high Performance Liquid Chromatography tandem Mass Spectrometry method were used to realize qualitatively and quantitative analysis in the same time. This study includes the following five components: First. Determination of organic solvent residue in Betahistine Hydrochloride by Headspace Gas Chromatography.The simultaneous determination both of isopropyle alcohol and chloroform was realized by Headspace Gas Chromatography, a good linear relation ship was made among each corresponding concentration range, this method is simple and accurate. Second. RP-HPLC for the determination of the content in Betahistine Hydrochloride and its Tablet.Non-aqueous titration for determination of content of Betahistine Hydrochloride in the Chinese Pharmacopoeia provision(2005), this methed's specificity is poor, impurities with similar structure would interfere the determination result, the determination of Betahistine Hydrochloride Tablet was used by UV in Chinese Pharmacopoeia provision (2005).In this paper Diamonsial (?)C18 (250 mm×4.6 mm,5μm) column was used, methanol-0.01 mol. L-1 ammonium acetate (0.05% heptane sulfonic,0.2% triethylamine, adjust pH to 3.5 with glacial acetic acid) (20:80) as mobile phase, column temperature 30℃, the flow rate is 1.0 mL. min-1, detection wavelength is 261 nm. To peak area (A) with the standard series of concentrations (C) linear regression, regression equation was A=19927C+13958,r=1.0. That Betahistine Hydrochloride in the range of 1-400mg. L-1concentrate a good linear relationship. Third. RP-HPLC method for the determination of the content of Betahistine Hydrochloride Injections.Agilent AICHROMBond C18 (250 mm×4.6 mm,5μm)column was used. Methanol-0.01 mol. L-1ammonium acetate (0.2% triethylamine,pH adjusted by glacial acetic acid to 3.5) (20:80) as mobile phase, column temperature is 30℃, the flow rate is 0.8 mL·min-1, detection wavelength 261 nm. Betahistine Hydrochloride in a concentration range of 1.05-314.5mg. L-1, with peak area (A) with the standard series of concentrations (C) linear regression,regression equation was A=32923C+2354.8,r=0.9999. The appropriate concentration range of linear relationship is good. Forth. Research of related substances in Betahistine HydrochlorideUsing HPLC-MS analysis of the main related substances, the results showed that Betahistine Hydrochloride and its Tablets were not detected with impurities, but there is one impuritie in Betahistine Hydrochloride Injection, which contain a molecular ion m/z106.20, and it UV maximum absorption wavelength was 286nm.Thin-layer chromatography and liquid-liquid extraction Preparation of the separation of impurities. Four spectrum(UV,IR,NMR,MS) utilization Confirmed that the impurity is 2-vinyl pyridine. This is the first time to found the impurity's Chemical Structure in Betahistine Hydrochloride destroyed by heat. Fifth. UPLC-MS method for the determination of Betahistine Hydrochloride Injection related substances 2-vinyl pyridine's content.This is the first time to set up a methed which for the Ultra High Performance Liquid Chromatography tandem Mass Spectrometry (UPLC-MS) method to determine related substances 2-vinyl pyridine in Betahistine Hydrochloride Injection at the same time qualitative and quantitative analysis. This methed provid detection basis for Betahistine Hydrochloride and its Injection during them production processes for quality control testing.
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