Determination Of Residual Organic Solvents In Traditional Chinese Medicine Extract

Object:In recent years, the quality standard of traditional Chinese medicine, which has been widely used in medicine, food, cosmetics and health products, etc., has been strict with all countries severely. The residual organic solvent in traditional Chinese medicine extract is defined as organic volatile chemicals that is used or produced in the process of production and could not be completely removed. It has potential drug toxicity, and it is not only affects the stability of traditional Chinese medicine extract, but it is also harmful to the health of patients. Toxicity and carcinogenesis of the residual organic solvent have caused medical attention increasingly. International Conference on Harmonization of technical requirements for registration of pharmaceuticals for human use(ICH) guiding principles points out that the schedules Ⅰ and Ⅱ organic solvents should be avoided to maintain the image of the traditional Chinese medicine: “green, environmental, healthy”. Consequently, the residual solvent content in the traditional Chinese medicine extract should be determined in practice to make a reasonable judgment and guarantee the quality of traditional Chinese medicine extract.The detection methods are varied during the history of the residual solvent analysis. Currently, Gas Chromatography has been generally adopted by all national pharmacopoeias. In this paper, the headspace capillary gas chromatography, which is usually used in the determination of residual organic solvents in drugs but rarely used in the determination of residual organic solvents in traditional Chinese medicine extract, was employed to detected the residual solvents, such as methanol, ethanol, ethyl acetate, dichloromethane, and chloroform, in Rhubarb Extract, Coptis Root extract, Schisandra chinensis extract, Artemisinin extract and Catharanthus Roseus Extract. Most components in traditional Chinese medicine extract are complex. Some are known and some are unknown, but all of them are insoluble. On the premise of the component characteristics of these five kinds of extracts, the characteristics of the measured residual solvents, and the interaction between them, the best solvent, headspace conditions and chromatographic conditions have been obtained. This study aims to provide data support for the quality standard of traditional Chinese medicine extract.Methods:1 Collect Rhubarb extract, Coptis Root extract, Schisandra chinensis extract, Artemisinin extract, and Catharanthus Roseus Extract.Rhubarb Extract, Schisandra chinensis extract and Artemisinin extract are from Changsha Zhong Ren Biotechnology Co.,Ltd.; Fluid of Coptis Root extract comes from Shijiazhuang fourth pharmaceutical factory; Coptis Root extract is homemade; Catharanthus Roseus Extract is from Shanxi Pioneer Biotech Co.,Ltd.2 The residual organic solvents in five kinds of Traditional Chinese medicine extract are determined by GC7900 Gas Chromatograph and DK-3001 B type semi automatic headspace sampler.3 By using Gas Chromatography. The column was ZB-1 capillary column, the detector is Hydrogen flame ionization detector, column temperature is programmed heating, the carrier gas was nitrogen, the inlet temperature of 200℃, the detector temperature of 230℃. To separate and determine ethanol and ethyl acetate residues in Rhubarb Extract, Schisandra chinensis extract and Coptis Root extract.4 By using Gas Chromatography. The column was DB-624 capillary column, the detector is Hydrogen flame ionization detector, column temperature is programmed heating, the carrier gas was nitrogen, the inlet temperature of 200℃, the detector temperature of 220℃, To separate and determine ethyl acetate, chloroform residual in Artemisinin extract and methanol, ethanol, dichloromethane, chloroform residual in Catharanthus Roseus Extract.65The chromatogram are analyzed by using D7900 chromatography workstation, the dates are analyzed by using excel statistical software.Results:1 In this chromatographic condition, the linear range of the measuring ethanol and ethyl acetate in Schisandra chinensis extract, Rhubarb Extract and Coptis Root extract were 0.0255~1.02mg/m L(r2=0.9985) and 0.0258~1.03mg/m L(r2=0.9998); The average recovery rate of ethanol and ethyl acetate in Schisandra chinensis extract were 98.9% and 110%, the average recovery of ethanol and ethyl acetate in Coptis Root extract were 102% and 111%, the average recovery of ethanol and ethyl acetate in Rhubarb extract were 101% and 99.1%(all RSD <5.0%), two kinds of organic solvent residues in three samples all meet the requirements of the China Pharmacopoeia.2 In this chromatographic condition, the ethyl acetate and chloroform build a good linear relationship in the range of 0.429~21.5mg/m L(r2=0.9956) and 5.19~ 260ug/m L(r2=0.9997), the average recovery were 99.0% and 99.0%, RSD were 1.97% and 3.21%, Residues amount of the organic solvent in Artemisinin extract all meet ICH and GMP requirements.3 In the method that is determination of residual solvents in Catharanthus Roseus Extract, the solvent peaks have good separation, the linear range of methanol, ethanol, dichloromethane and chloroform were 0.299~5.98mg/m L(r2=0.9998), 0.490~9.80mg/m L(r2=0.9993), 0.0681~1.36mg/m L(r2=0.9991), 9.04~181ug/m L(r2=0.9992), RSD < 5%, the average recovery were 101%, 104%, 100%, 111%.Conclusion:1 Schisandra chinensis extract, Rhubarb extract and Coptis Root extract were dissolved in DMF, which can make solvent better volatile, almost has no pollution for chromatographic system, and is the ideal headspace solvent. The method is simple, sensitive and accurate, and can be used for the determination of residual organic solvents in three kinds of extracts.2 The residual solvents in Artemisinin extract and Catharanthus Roseus Extract are determined by headspace gas chromatography with hydrogen flame ionization detector and DB-624 capillary chromatographic column. Through methodology validation, there is a good linear relationship and high degree of separation. The method is accurate and feasible.