摘要
目的建立测定枸橼酸莫沙必利片有关物质检测条件下特定杂质莫沙必利柠檬酰胺2个色谱峰的超高效液相色谱-四极杆飞行时间质谱(UPLC-Q-TOF-MS)法。方法HPLC条件,色谱柱为Agilent C18柱(150 mm×4.6 mm,5μm),流动相为枸橼酸盐溶液-乙腈(梯度洗脱),流速为1.0 mL/min,检测波长为274 nm,柱温为30℃,进样量为10μL;UPLC-Q-TOF-MS条件,色谱柱为YMC-Triant C18柱(150 mm×2.1 mm,1.9μm),检测器为DAD检测器,流动相为含0.1%甲酸的10 mmol/L乙酸铵(A)-乙腈(B)、梯度洗脱,流速为0.5 mL/min,检测波长为274 nm,柱温为40℃,进样量为0.5μL。电喷雾离子源正离子扫描模式(ESI+),二级质谱碰撞能量30 eV,毛细管电压4 kV,锥孔电压45 V,碎裂电压60 V,干燥气流速8 mL/min,干燥气温度300℃,雾化气压力35 psi,扫描模式MS/MS;扫描范围m/z 50~700;按不加校正因子的主成分自身对照法计算杂质莫沙必利柠檬酰胺含量。结果莫沙必利柠檬酰胺出现双峰,且与其他杂质的分离良好;莫沙必利柠檬酰胺质量浓度在0.35~7.00μg/mL范围内与峰面积线性关系良好(r=0.9997);检测限为0.70 ng,定量限为2.8 ng;精密度试验结果的RSD小于4.00%;流动相中枸橼酸盐溶液pH在3.8~4.2时所建方法耐用性良好。通过UPLC-Q-TOF-MS推测,莫沙必利柠檬酰胺的2个色谱峰为其在液相色谱条件下生成羧酸钠盐后不完全解离成的2种型式。结论所建方法适合枸橼酸莫沙必利片中特定杂质莫沙必利柠檬酰胺的检测,该研究可为制剂后续质量控制研究提供参考。
Objective To establish an ultra-high performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry(UPLC-Q-TOF-MS)method for the detection of two chromatographic peaks of specific impuritie(mosapride citric amide)under the detection conditions of related substances in Mosapride Citrate Tablets.Methods High-performance liquid chromatography(HPLC)conditions were as follows:the chromatographic column was Agilent C18 column(150 mm×4.6 mm,5μm),the mobile phase was citrate solution-acetonitrile with gradient elution,the flow rate was 1.0 mL/min,the detection wavelength was 274 nm,the column temperature was 30℃,and the injection volume was 10μL.UPLC-Q-TOF-MS conditions were as follows:the chromatographic column was YMC-Triant C18 column(150 mm×2.1 mm,1.9μm),the detector was diode array detector(DAD),the mobile phase was 10 mmol/L ammonium acetate containing 0.1%formic acid(A)-acetonitrile(B)with gradient elution,the flow rate was 0.5 mL/min,the detection wavelength was 274 nm,the column temperature was 40℃,and the injection volume was 0.5μL.Electron spray ionization(ESI+)with positive ion scanning mode was adopted,the collision energy of the secondary mass spectrometry was 30 eV,the capillary voltage was 4 kV,the taper hole voltage was 45 V,the fragmentation voltage was 60 V,the flow rate of drying air was 8 mL/min,the temperature of drying gas was 300℃,the pressure of atomizing gas was 35 psi,the scanning mode was MS/MS,and the scanning range was m/z 50-700.The content of impurity mosapride citric amide was calculated by the main component self-contrast method without calibration factor.Results Mosapride citric amide showed double peaks and was well separated from impurities.The linear range of mosapride citric amide was 0.35-7.00μg/mL(r=0.9997).The limit of detection(LOD)was 0.70 ng and the limit of quantification(LOQ)was 2.8 ng.The RSD of the precision test was less than 4.00%.The mobile phase of citrate solution had good durability with pH of 3.8-4.2.According to UPLC-Q-TOF-MS,the
作者
刘阿利
王雪
张贵民
LIU Ali;WANG Xue;ZHANG Guimin(Lunan BeiTe Pharmaceutical Co.,Ltd.,Linyi,Shandong,China 276006;National Engineering and Technology Research Center of Chirality Pharmaceutical,Linyi,Shandong,China 276006;Shandong Engineering Research Center for Development of New Pharmaceutical Preparations,Linyi,Shandong,China 276006)
出处
《中国药业》
CAS
2023年第2期78-82,共5页
China Pharmaceuticals
基金
山东省临沂市兰山区科技发展计划项目[1935]。
