Stiripentol Quality Standard Study

Stiripentol is a new antiepileptic drug, its mechanism of action is inhibition of cytochrome P450, when it settled with valproate and oxygen different combination, stiripentol for severe myoclonic epilepsy have a good therapeutic effect. In this experiment,I will analyze for APIs,including drug traits, drug identification, inspection items, such as determination, analysis and study of its quality standards.Objective: To establish the quality standard of division for Stiripentol.Methods: Using the method of its characters “Chinese Pharmacopoeia” provisions in the identification, including appearance, melting point, solubility, hygroscopicity and specific rotation.To identify stiripentol by HPLC and UV.To check the relevant material, residual solvent, water, pyrotechnic residues and heavy metals.The contents of stiripentol are determined by HPLC, using a mobile phase acetonitrile: water(different ratio), stationary phase: Eighteen alkyl bonded silica gel stationary phase(4.6×250mm, 5μm), the detection wavelength: 270 nm, sample size: 10μl, flow rate: 1.0ml/min. Using 30 ℃column temperature test.Results: In accordance with the "2010" version of the “China Pharmacopoeia” requirements for stiripentol appearance, melting point, solubility, hygroscopicity and specific rotation were identified, the results showed that stiripentol test samples and the standard is consistent in appearance; melting point between 75 to 78 ℃; The sample is soluble in acetonitrile, methanol, acetone, chloroform and DMF, insoluble in hydrochloric acid 0.1mol/L and water; moisture absorption between the weight of 1.6%-2.0%; rotation between-137 ~-139 degrees.The above results are consistent with the requirements.Samples are identified by HPLC and UV identification methods, separation and mapping standard consistency, UV absorption maxima is 270 nm, indicates that the sample and the standard are a kind of material.The material separation degree reached 1.5, the content of impurities by principal components without calibration factor were calculated, were lower than 0.05%, conforming to the standard.The contents of residual organic solvents by external standard method for the determination of methanol, ethanol, isopropanol, acetone, benzene and two chlorine ethane show that:Less than 0.3% of methanol, ethanol, acetone and isopropanol are less than 0.5%, less than 0.0002% of benzene, two chlorine ethane are lower than 0.0005%, conforming to the standard.Determination of the water content less than 0.5% water shows that the samples are conforming to the standard.Pyrotechnic residues by determination of residue content is less than 0.1%, in line with the standard.By measuring the heavy metal “China Pharmacopoeia” 2010 two appendix VIII H second method, visual analysis results, formula of solution color slightly pale in color of lead standard solution, to meet the requirements of heavy metals.Determination of content of stiripentol in the concentration of 0.3 ~ 5.0 mg/ml range, the linear relationship is between the concentration and peak area, good r=0.9991, good linearity. The different flow rate, column temperature, good separation, Waters, Welchrom, Thermo column durability better.Conclusion: The differential method is effective and feasible, for its appearance, melting point, solubility, hygroscopicity and the identification results are consistent with the requirements of the specific rotation. Check the related substances, residual solvent, water, pyrotechnic, heavy metal residue results can meet the requirements.HPLC determination of the content is of high sensitivity, good linearity, good accuracy, high recovery, good repeatability, high precision.This experiment can be used in our research for the quality standard of stiripentol.