Determination Of N-methylbenzylamine In Levetiracetam By Ion Chromatography And High Performance Liquid Chromatography

Levetiracetam is an anti-epileptic drug with a new anti-epileptic mechanism,which can effectively control seizures.N-methylbenzylamine is a common pharmaceutical intermediate and organic solvent.N-methylbenzylamine is used in the synthesis of levetiracetam,and N-methylbenzylamine and sodium nitrite can synthesize the strong carcinogen methylbenzylnitrosamine in the body,so for the synthesis of drugs Nmethylbenzylamine levels need to be carefully monitored in the process,drug substance and final formulation.At present,there are few literatures on the analysis method of Nmethylbenzylamine,so this paper mainly analyzes the research status of Nmethylbenzylamine at home and abroad,and establishes the determination of Nmethylbenzyl in levetiracetam.The two methods of ion chromatography and high performance liquid chromatography for amine content,of which the method established in this paper for the detection of N-methylbenzylamine by high performance liquid chromatography can also be applied to the wastewater discharged from the Nmethylbenzylamine raw material production plant Determination of N-methylbenzylamine content.The main contents and conclusions of the study are as follows:(1)Determination of N-methylbenzylamine in levetiracetam by ion chromatographyAn ion chromatograph with a tandem suppression conductivity detector detects Nmethylbenzylamine in levetiracetam.The Dionex IonPacTMCS17 column was used as the analytical column,and the Dionex IonPacCG17 column was used as the guard column,0.003mol/L methanesulfonic acid solution(containing 30% of acetonitrile)as the eluent,a gradient elution,a flow rate of 0.8 mL/min,an injection volume of 100 ?L,and direct injection determination.This method focuses on comparing the detection effect of the conductivity detector and the ultraviolet detector,and finally determines that the conductivity detector was used for detection.Under the conditions of this method,the sample matrix and common cations did not interfere with the determination;the linear relationship was good within the range of 0.05 ?g/mL?5 ?g/mL(r = 0.9996);the limit of quantification was 0.05?g / mL;The recovery of levetiracetam was 99.8% ? 108.1%(n = 9).The method is simple,accurate,high sensitivity,good reproducibility,and meets the detection requirements.(2)Determination of N-methylbenzylamine in levetiracetam by high performance liquid chromatographyA high performance liquid chromatography-ultraviolet detection method for analyzing the content of N-methylbenzylamine in levetiracetam was established.For pretreatment,dichloromethane was used for extraction from water.An Agilent ZORBAX ODS C18 column(3.0 × 150 mm,5 ?m)was used as the analytical column.Methanol and water were used as the eluent.The gradient was eluted at a flow rate of 0.6 mL/min.The amount was 10 ?L,and the ultraviolet detector detects at a wavelength of 244 nm.The results show that the sample matrix of this method has no interference and good specificity;the linear relationship was good within the range of 0.05 ?g/mL?3 ?g/mL(r = 0.9971);the limit of quantification was 0.08 ?g/mL;The recovery of levetiracetam was 76.5%?86.4%(n = 9).This method is economical and applicable,with good repeatability,sensitivity and accuracy,and can be used for the analysis of N-methylbenzylamine in levetiracetam.And this method can also be used to detect N-methylbenzylamine in the N-methylbenzylamine production plant wastewater,providing a reliable detection method for the detection of Nmethylbenzylamine in the environment.