Research And Application Of Drug Quality Control And In Vivo Metabolism Based On The Technology Of GC-MS And GC-FID

Gas chromatography is a suitable method for the analysis of volatile components. The development of gas chromatography is earlier than that of liquid chromatography. And the degree of commercialization is also high. Through the combination of different analytical techniques and detectors and the development of different pretreatment methods, the application of gas chromatography has become more and more widely. This research based on the technology of GC-MS and GC-FID to study three kinds of drugs, which provide examples of the application of this technology in the research on drug quality control and in vivo metabolism. The specific research contents are as follows:1. GC-MS/FID in analysis of impurities in Tenofovir disoproxil fumarateGC-MS method was used for qualitative analysis of volatile impurities in the Tenofovir disoproxil fumarate (TDF), and the sample was determined to have a small amount of isopropanol. The study has first established a simultaneous determination method for the eight organic solvents in the TDF of acetone, isopropanol, dichloromethane, isopropyl ether, ethyl acetate, N,N-dimethylformamide, chloromethyl isopropyl carbonate and N-methyl pyrrolidone by GC-FID. The method can be applied to the detection of residual solvents in TDF by complete methodology. Eight solvents can be completely separated, the method had a good linearity(R2= 0.9990-0.9998), precision of RSD is less than 3%, the average recovery rate is 99.18%～101.87%. The residual organic solvents in the three batch of samples were within the prescribed limits. The result shows that the method is sensitive, accurate and reliable, which can be used for the detection of eight different organic solvents in TDF.2. Analysis of volatile components of Zhi-Zi-Hou-Pu decoction and optimization of extraction method of the Hpid soluble componentsUsing steam distillation method to extract the volatile oil from Zhi-Zi-Hou-Pu decoction (ZZHPD), each single herb and herb-pairs. The qualitative analysis and the relative content of the components in the volatile oil were analyzed by GC-MS.121 volatile oil components has been identified. There were 57,68,41 and 82 volatile constituents in Gardenia, Mangnolia officinalis, Fructus aurantii immaturus and ZZHPD. The main components of ZZHPD include D-limonene, β-eudesmol, a-eudesmol and y-eudesmol, which components accounted for 80.37% of total volatile oil, which shows that these components is the main component of the essential oil of ZZPHD.On the basis of this, the accelerated solvent extraction and dispersive liquid-liquid microextraction (ASE-DLLME) is used in experiment for the first time to extract the effective components of ZZHPD. Optimized the method of ASE-DLLME by single factor test and response surface design. The optimization conditions of ASE and DLLME to the extraction of the components in ZZHPD are as follows:55% ethanol as the solvent, the temperature of the extraction is 160℃, the extraction time is 8 min,1cycle; as for the DLLME, the samples were diluted, which contain 20%ethanol, 100μL ethanol as the dispersant,30 μL dichloromethane as the extractant. At the same time, there were 61 components identified from the sample extracted by ASE. The main components are magnolol (44.48%) and honokiol (36.55%), which accounted for 81.03% of the total extract. Compared with other organic solvent extraction method, ASE-DLLME in a large extent reduced herbs in the loss of volatile components, and effectively extract lipid soluble components from Chinese herbal medicines. In a short, ASE-DLLME can provide technical support for the study of lipid soluble constituents of ZZHPD.3. Plasma pharmacokinetics of volatility components of Suxiao Jiuxin pills and its metabolism in SD ratThe volatility components of Suxiao Jiuxin pills(SJP) in rat plasma was analyzed by GC-MS. The plasma samples containing camphor, isoborneol and borneol. But camphor is the metabolite. The study has established a rapid and sensitive method for the determination of camphor, isoborneol and D-borneol in SD rat plasma. The complete method validation shows that the method can meet the technical requirements of preclinical pharmacokinetic studies, which also can be used for the pharmacokinetic study of camphor, isoborneol and borneol in SD rats in vivo. The method was established for the first time to determine the content of the three components in SD rat’s plasma administrated with SJP and to determine the pharmacokinetic parameters of the components in SD rat’s plasma. Result shows that the trend of absorption and metabolism of D-borneol and isoborneol is basically the same. The concentration of camphor in vivo plasma also along with the change of borneol. The Tmax of the three components were less than 1.5h, which indicated that the three components have fast absorption in vivo in SD rat.