HPLC法测定奥卡西平及其制剂中有关物质  

Determination of the related substances in oxcarbazepine and its preparation by HPLC

作　　者：朱晓月 高青 朱莉娜 王雪莉 胡琴 张喆 ZHU Xiaoyue;GAO Qing;ZHU Lina;WANG Xueli;HU Qin;ZHANG Zhe(Beijing Institute for Drug Control,NMPA Key Laboratory for Research and Evaluation of Generic Drugs,Beijing Key Laboratory of Analysis and Evaluation on Chinese Medicine,Beijing 102206,China)

机构地区：[1]北京市药品检验研究院,国家药品监督管理局仿制药研究与评价重点实验室,中药成分分析与生物评价北京市重点实验室,北京102206

出　　处：《中国药品标准》2023年第2期144-148,共5页Drug Standards of China

摘　　要：目的:建立使用C 18色谱柱同时测定奥卡西平及其制剂中8个杂质的高效液相色谱法。方法:采用ACE Excel C 18(4.6 mm×150 mm,3μm)色谱柱,流速1.0 mL·min^(-1),以6.8 g·L^(-1)磷酸二氢钾溶液(每1000 mL加三乙胺2 mL,用磷酸调pH 6.0)为流动相A,乙腈-甲醇(11∶8)为流动相B,梯度洗脱,检测波长240 nm,柱温45℃。结果:奥卡西平与8个杂质分离度良好,奥卡西平和卡马西平分别在0.05~4.0μg·mL^(-1)和0.08~40μg·mL^(-1)浓度范围内呈现良好线性(r≥0.9999),奥卡西平和卡马西平的定量限分别为1.03、0.65 ng,检测限分别为0.34、0.33 ng。共测定奥卡西平原料2个企业5批样品、奥卡西平片2个企业6批样品,其中1批原料检出杂质E,含量为0.004%;3批片剂检出卡马西平,含量分别为0.008%、0.005%、0.006%;1批片剂检出杂质C和杂质D,含量为0.006%、0.005%;单个最大未知杂质含量在0.02%~0.20%范围内,杂质总量在0.02%~0.32%范围内。结论:本法使用小粒径色谱柱节省检测时间,为进一步完全奥卡西平及其制剂的质量评价提供依据。Objective:To establish an HPLC method for the determination of eight related substances in oxcarbazepin and its preparation by HPLC.Methods:The analyte was gradient eluted on the ACE Excel C 18(4.6 mm×150 mm,3μm)with mobile phase A[6.8 g·L^(-1)potassium dihydrogen phosphate solution(containing 2 mL of triethylamine in 1000 mL,and adjusted to pH 6.0 with phosphoric acid)]and mobile phase B[acetonitrile-methanol(11∶8)]at a flow rate of 1.0 mL·min^(-1).The detection wavelength was 240 nm.The column temperature was 45℃.Results:The resolution factor between the peaks complied with the related requirements.The method had good linear relationship(r≥0.9999)at the 0.05-4.0μg·mL^(-1)of oxcarbazepine and 0.08-40μg·mL^(-1)of carbamazepine.Limit of quantitation about oxcarbazepine and carbamazepine were 1.03 ng and 0.65 ng.Limit of detection about oxcarbazepine and carbamazepine were 0.34 and 0.33 ng.5 batches of oxcarbazepine materials from 2 enterprises and 6 batches of oxcarbazepine tablets from 2 enterprises were determined.Impurity E was determined in 1 batch of oxcarbazepine materials,which content was 0.004%.Carbamazepine was determined in 3 batches of oxcarbazepine tablets,which contents were 0.008%,0.005%and 0.006%,respectively.Impurity C and Impurity D were determined in 1 batch of oxcarbazepine tablets,which contents were 0.006%and 0.005%.The content of any individual unspecified impurity was 0.02%-0.20%.The content of total impurities was 0.02%-0.32%.Conclusion:The method adopted small particle size column is used to save time.It provides the basis for improving the quality evaluation of oxcarbazepine and its preparation.

关 键 词：有关物质 奥卡西平 精神类药 高效液相色谱 梯度洗脱 

分 类 号：R921.2[医药卫生—药学]