LC-MS/MS法同时测定艾司奥美拉唑钠原料药及其制剂中3种杂质的含量
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摘要
目的:建立同时测定艾司奥美拉唑钠原料药及其制剂中杂质E、杂质Ⅰ和杂质Ⅳ含量的方法。方法:采用液相色谱-串联质谱法。色谱柱为Agela VenusiL MP C18,流动相为乙腈-水(梯度洗脱),流速为0.2 mL/min,柱温为35℃,进样量为1μL;离子源为电喷雾离子源,检测方式为负离子模式,工作模式为多反应监测模式,用于定量分析的离子对分别为m/z 360.1→194.0(杂质E)、m/z 375.8→210.7(杂质Ⅰ)、m/z 330.2→312.1(杂质Ⅳ)。结果:杂质E、杂质Ⅰ、杂质Ⅳ检测质量浓度的线性范围分别为0.001 26～0.044 80μg/mL(r=0.994 7)、0.001 34～0.045 2μg/mL(r=0.992 8)、0.018 9～1.260 00μg/mL(r=0.991 4);定量限分别为0.001 26、0.001 34、0.018 9μg/mL,检测限分别为0.000 41、0.000 44、0.006 3μg/mL;精密度、重复性试验的RSD均小于4%,稳定性试验杂质E、杂质Ⅰ的RSD<10%(n=5),杂质Ⅳ的RSD>15%(n=7);加样回收率分别为87.69%～100.72%(RSD=4.29%,n=9)、90.04%～100.63%(RSD=3.67%,n=9)、93.58%～101.86%(RSD=2.66%,n=9)。结论:该方法准确、快速、灵敏、专属性强,可用于同时测定艾司奥美拉唑钠原料药及其制剂中3种杂质的含量。
OBJECTIVE:To establish a method for simultaneous determination of impurity E,impurity Ⅰ and impurity Ⅳ in crude drug and preparation of esomeprazole sodium. METHODS:LC-MS/MS method was adopted. The separation was performed on Agela VenusiL MP C18 column with mobile phase consisted of acetonitrile-water(gradient elution)at the flow rate of 0.2 mL/min. The column temperature was 35 ℃,and the sample size was 1 μL;analytes were analyzed by electro-spray ionization(ESI)in the multiple reaction monitoring mode,negative ion. The precursors of production transitions m/z 360.1→194.0(impurity E),m/z375.8→210.7(impurity Ⅰ),m/z 330.2→312.1(impurity Ⅳ)were used to measure impurity. RESULTS:The linear range of impurity E,impurity Ⅰ and impurity Ⅳ were 0.001 26-0.044 80 μg/mL(r=0.994 7),0.001 34-0.045 2 μg/m L(r=0.992 8)and0.018 9-1.260 00 μg/m L(r=0.991 4). The limit of quantitation were 0.001 26,0.001 34,0.018 9 μg/m L;the detection limits were0.000 41,0.000 44,0.006 3 μg/m L. RSDs of precision and reproducibility tests were all lower than 4%;RSDs of stability tests of impurity E and impurity Ⅰ were all lower than 10%(n=5),and that of impurity Ⅳ was higher than 15%(n=7). The average recoveries were 87.69%-100.72%(RSD=4.29%,n=9),90.04%-100.63%(RSD=3.67%,n=9)and 93.58%-101.86%(RSD=2.66%,n=9). CONCLUSIONS:The method is accurate,rapid,sensitive,selective and suitable for the content determination of3 impurities in crude drug and preparation of esomeprazole sodium.
OBJECTIVE:To establish a method for simultaneous determination of impurity E,impurity Ⅰ and impurity Ⅳ in crude drug and preparation of esomeprazole sodium. METHODS:LC-MS/MS method was adopted. The separation was performed on Agela VenusiL MP C18 column with mobile phase consisted of acetonitrile-water(gradient elution)at the flow rate of 0.2 mL/min. The column temperature was 35 ℃,and the sample size was 1 μL;analytes were analyzed by electro-spray ionization(ESI)in the multiple reaction monitoring mode,negative ion. The precursors of production transitions m/z 360.1→194.0(impurity E),m/z375.8→210.7(impurity Ⅰ),m/z 330.2→312.1(impurity Ⅳ)were used to measure impurity. RESULTS:The linear range of impurity E,impurity Ⅰ and impurity Ⅳ were 0.001 26-0.044 80 μg/mL(r=0.994 7),0.001 34-0.045 2 μg/m L(r=0.992 8)and0.018 9-1.260 00 μg/m L(r=0.991 4). The limit of quantitation were 0.001 26,0.001 34,0.018 9 μg/m L;the detection limits were0.000 41,0.000 44,0.006 3 μg/m L. RSDs of precision and reproducibility tests were all lower than 4%;RSDs of stability tests of impurity E and impurity Ⅰ were all lower than 10%(n=5),and that of impurity Ⅳ was higher than 15%(n=7). The average recoveries were 87.69%-100.72%(RSD=4.29%,n=9),90.04%-100.63%(RSD=3.67%,n=9)and 93.58%-101.86%(RSD=2.66%,n=9). CONCLUSIONS:The method is accurate,rapid,sensitive,selective and suitable for the content determination of3 impurities in crude drug and preparation of esomeprazole sodium.
引文
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[12]张闪闪,吴燕,张福成.高效液相色谱法测定埃索美拉唑镁肠溶片的有关物质[J].中国医院药学杂志,2016,36(19):1704-1708.
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[15]李婷婷,郑子栋.RP-HPLC法测定埃索美拉唑钠的有关物质[J].药物分析杂志,2013,33(4):656-660.
[16]宁二娟,王庆鹏,王玉拓,等.HPLC法测定埃索美拉唑镁肠溶胶囊的有关物质[J].分析试验室,2015,34(2):209-211.
[17]姜鹰雁,耿志鹏,刘燕,等.顶空气相色谱法同时测定艾司奥美拉唑镁原料药中6种有机溶剂的残留量[J].中国药房,2017,28(15):2093-2096.
[2]张颖慧,李良平.伊托必利联合艾司奥美拉唑镁治疗食管运动功能障碍致胃食管反流病的临床观察[J].中国药房,2017,28(35):4974-4977.
[3]国家药典委员会.中华人民共和国药典:二部[S].2015年版.北京:中国医药科技出版社,2015:127-128.
[4]国家食品药品监督管理局.化学药物杂质研究技术指导原则[S].2005.
[5]ICH.Harmonized tripartite guideline:impurities in new drug substances[S].2006-10-25.
[6]ICH.Harmonized tripartite guideline:impurities in new drug products[S].2006-06-02.
[7]马延,王媛,罗智敏,等.HPLC法测定埃索美拉唑钠的有关物质[J].西北药学杂志,2016,31(2):154-157.
[8]郑景哲,牟玲丽.RP-HPLC法测定埃索美拉唑镁的含量及有关物质[J].湖南师范大学学报(医学版),2014,11(1):90-92、96.
[9]陈芳晓,王磊,曾环想,等.埃索美拉唑镁肠溶胶囊有关物质的HPLC法测定[J].中国医药工业杂志,2014,45(6):560-563.
[10]陈赛赛,顾文平.艾司奥美拉唑钠有关物质的反相-HPLC法测定[J].科技创新与应用,2016(17):52-53.
[11]夏品思,闫冬,姚宏涛,等.反相高效液相色谱法测定注射用埃索美拉唑钠有关物质[J].中南药学,2014,12(11):1131-1135.
[12]张闪闪,吴燕,张福成.高效液相色谱法测定埃索美拉唑镁肠溶片的有关物质[J].中国医院药学杂志,2016,36(19):1704-1708.
[13]秦序锋,王开颖,方明春,等.注射用埃索美拉唑钠中杂质的检查及控制[J].山东化工,2014,43(3):21-25.
[14]徐晓娟,唐云.注射用埃索美拉唑钠的研制及其稳定性考察[J].科技创新导报,2014(34):206-209.
[15]李婷婷,郑子栋.RP-HPLC法测定埃索美拉唑钠的有关物质[J].药物分析杂志,2013,33(4):656-660.
[16]宁二娟,王庆鹏,王玉拓,等.HPLC法测定埃索美拉唑镁肠溶胶囊的有关物质[J].分析试验室,2015,34(2):209-211.
[17]姜鹰雁,耿志鹏,刘燕,等.顶空气相色谱法同时测定艾司奥美拉唑镁原料药中6种有机溶剂的残留量[J].中国药房,2017,28(15):2093-2096.