2D-LC-QTOF-MS法鉴定酒石酸托特罗定片辅料中未知杂质及来源分析  

Identification and Source Analysis of Unknown Impurities in the Excipients of Tolterodine Tartrate Tablets by 2D-LC-QTOF-MS Method

作　　者：刘晓佳 潘芳芳 徐东海 柳文媛[1,4] 邵鹏 LIU Xiaojia;PAN Fangfang;XU Donghai;LIU Wenyuan;SHAO Peng(China Pharmaceutical University,Nanjing,Jiangsu,China 210009;Zhejiang Institute for Food and Drug Control,Hangzhou,Zhejiang,China 310052;NMPA Key Laboratory for Core Technology of Generic Drug Evaluation,Hangzhou,Zhejiang,China 310052;Zhejiang Research Center for API Security,Hangzhou,Zhejiang,China 310051;Key Laboratory of Drug Contacting Materials Quality Control of Zhejiang Province,Hangzhou,Zhejiang,China 310051)

机构地区：[1]中国药科大学,江苏南京210009 [2]浙江省食品药品检验研究院,浙江杭州310052 [3]国家药品监督管理局仿制药评价关键技术重点实验室,浙江杭州310052 [4]浙江省原料药安全研究中心,浙江杭州310051 [5]浙江省药品接触材料质量控制研究重点实验室,浙江杭州310051

出　　处：《中国药业》2024年第16期68-73,共6页China Pharmaceuticals

基　　金：2022年国家药品抽检计划[国药监药管[2022]1号]。

摘　　要：目的建立鉴定酒石酸托特罗定片辅料中未知杂质的中心切割在线二维液相色谱-四极杆飞行时间质谱(2D-LC-QTOFMS)法,并归属杂质来源。方法一维液相色谱采用Waters XBridge-C_(18)柱(250 mm×4.6 mm,5μm),流动相为乙腈-水-高氯酸(200∶800∶1.5,V/V/V)-乙腈(梯度洗脱),流速为1.0 mL/min,检测波长为220 nm,柱温为65℃,进样量为10μL;二维液相色谱采用Agilent Poroshell 120 EC-C_(18)柱(100 mm×2.1 mm,2.7μm),流动相为甲酸铵缓冲液(20 mmol/L甲酸铵溶液,用甲酸调pH至3.0)-乙腈(55∶45,V/V),流速为0.3 mL/min,检测波长为220 nm,柱温为25℃;质谱采用电喷雾离子源(ESI),正离子检测模式。结果鉴定了1个未知杂质的可能结构,确认该杂质由制剂的预混包衣剂辅料羟丙甲纤维素引入;检测了8家羟丙甲纤维素生产企业的产品,有1家企业检测出该杂质。结论该方法可用于酒石酸托特罗定片中未知杂质的在线定性鉴别。Objective To establish an online heart-cutting two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry(2D-LC-QTOF-MS)method for identifying the unknown impurities in the excipients of Tolterodine Tartrate Tablets,and to analyze the sources of impurities.Methods The one-dimensional liquid chromatography was performed on the Waters XBridge-C_(18) column(250 mm×4.6 mm,5μm),the mobile phase was acetonitrile-water-perchloric acid(200∶800∶1.5,V/V/V)-acetonitrile(gradient elution),the flow rate was 1.0 mL/min,the detection wavelength was 220 nm,the column temperature was 65℃,the injection volume was 10μL.The two-dimensional liquid chromatography was performed on the Agilent Poroshell 120 EC-C_(18) column(100 mm×2.1 mm,2.7μm),the mobile phase was ammonium formate buffer(20 mmol/L ammonium formate solution,adjusted to pH 3.0 with formic acid)-acetonitrile(55∶45,V/V),the flow rate was 0.3 mL/min,the detection wavelength was 220 nm,the column temperature was 25℃.The electron spray ionization(ESI)was adopted with positive ion detection mode.Results The possible structure of an unknown impurity was identified,and it was confirmed that the impurity was introduced by hydroxypropyl methylcellulose,a film-coated premix in the formulation.The hydroxypropyl methylcellulose of eight manufacturing enterprises was tested,and that of one enterprise was detected.Conclusion This method can be used for online qualitative identification of unknown impurities in Tolterodine Tartrate Tablets.

关 键 词：酒石酸托特罗定片 二维液相色谱-四极杆飞行时间质谱法 中心切割 辅料 羟丙甲纤维素 

分 类 号：R917[医药卫生—药物分析学] R927[医药卫生—药学]