Identification and Content Determination of Main Unknown Impurity in Oxiracetam Capsule / 中国药房

ABSTRACT

OBJECTIVE：To identify the main unknow impurity of Oxiracetam capsule and determine its content ，so as to improve the standard of quality control. METHODS ：Two-dimensional UPLC -IT-TOF-MS was adopted to qualitatively analyze the unknown impurity. One-dimensional liquid chromatogram analysis was performed on ST PAK C 18 ES column with mobile phase consisted of 0.02 mol/L sodium dihydrogen phosphate solution at the flow rate of 0.5 mL/min. The column temperature was set at 30 ℃，sample size was 20 μL. The detection wavelength was set at 210 nm. Two-dimensional liquid chromatogram analysis was performed on Techmate C 18-STⅡ column with mobile phase consisted of 0.02 mol/L ammonium acetate solution at the flow rate of 0.5 mL/min. The column temperature was 30 ℃. Mass spectrometry was adopted （electropray ionization source ，MS+ and MS － mode data acquisition ）. After the target impurity was located by one-dimensional liquid chromatography ，it was transferred to two-dimensional liquid chromatography-mass spectrometry system for qualitative analysis. The unknown impurity structure was inferred by means of molecular formula prediction module “Accurate Mass Calculator ”in LCMS Solution ，and the refined impurity products by preparation and purification were standardized and confirmed . The impurity content was determined by HPLC （with the same condition of one-dimensional liquid chromatography for qualitative analysis ）. RESULTS ：The main unknown impurity in Oxiracetam capsules is oxiracetam acid. The content of the refined product was 99.5％ after preparation and purification. The contents of oxiracetam acid in 9 batches of Oxiracetam capsules were 0.05％ -0.14％ . CONCLUSIONS ：The established two-dementional UPLC-IT-TOF-MS method can accurately locate the peak position of the impurity oxiracetam acid ，and analyze its structure，while the corresponding content determination method can better separate the impurity from the main drug and other components，with good sensitivity ，precision，repeatability，stability and accuracy. The quality of the finished product of Oxiracetam capsules can be well controlled by using above method .