气相色谱法同时测定尼尔雌醇原料药中7种有机溶剂的残留量
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摘要
目的:建立同时测定尼尔雌醇原料药中甲醇、乙醇、乙腈、异丙醇、甲苯、四氢呋喃和乙酸乙酯残留量的方法。方法:采用气相色谱法。色谱柱为DB-WAX毛细管柱,检测器为氢火焰离子化检测器,分流比为5∶1,载气为氮气(纯度:99.999%),流速为1.0 mL/min,进样量为1μL,直接进样,固定相为键合交联聚乙二醇,升温程序为初始温度40℃,保持5 min,以10℃/min速率升温至90℃,再以5℃/min速率升温至200℃,进样口温度为220℃,检测器温度为230℃。结果:甲醇、乙醇、乙腈、异丙醇、甲苯、四氢呋喃和乙酸乙酯的检测质量浓度线性范围分别为0.24～12.00μg/mL(r=0.999 7)、0.40～20.00μg/mL(r=0.999 5)、0.033～1.64μg/mL(r=0.999 8)、0.40～20.00μg/mL(r=0.999 5)、0.071～3.56μg/mL(r=0.999 6)、0.058～2.88μg/mL(r=0.999 8)、0.40～20.00μg/mL(r=0.999 7);定量限分别为0.24、0.40、0.033、0.40、0.071、0.058、0.40μg/mL,检测限分别为0.08、0.10、0.01、0.13、0.02、0.02、0.13μg/mL;精密度、稳定性、重复性试验的RSD均小于2%;加样回收率分别为98.17%～100.48%(RSD=0.92%,n=9)、97.77%～101.30%(RSD=1.32%,n=9)、97.56%～100.85%(RSD=1.20%,n=9)、98.64%～100.92%(RSD=0.87%,n=9)、98.54%～100.62%(RSD=0.76%,n=9)、98.26%～100.00%(RSD=0.74%,n=9)、98.30%～100.59%(RSD=0.76%,n=9)。结论:该方法灵敏度较高、准确度较好,可用于同时测定尼尔雌醇原料药中甲醇、乙醇、乙腈、异丙烷、甲苯、四氢呋喃和乙酸乙酯的残留量。
OBJECTIVE:To establish a method for simultaneous determination of residual methanol,ethanol,acetonitrile,isopropanol,methylbenzene,tetrahydrofuran and ethyl acetate in Nilethylenol raw material. METHODS:GC was performed. The determination was performed on DB-WAX capillary column. The detector was hydrogen flame ionization detector with split ratio of5∶1. The carrier gas was nitrogen(purity:99.999%)at the flow rate of 1.0 mL/min. The sample size was 1 μL,directly sampling with bonded crosslinked polyethylene glycol as stationary phase. The initial temperature was 40 ℃ and was maintained for 5 min,increased to 90 ℃ at 10 ℃/min,and then increased to 200 ℃ at 5 ℃/min. The temperature of injector was 220 ℃,and detector temperature was 230 ℃. RESULTS:The linear range was 0.24-12.00 μg/mL for methanol(r=0.999 7),0.40-20.00 μg/mL for ethanol(r=0.999 5),0.033-1.64 μg/mL for acetonitrile(r=0.999 8),0.40-20.00 μg/mL for isopropanol(r=0.999 5),0.071-3.56 μg/mL for methylbenzene(r=0.999 6),0.058-2.88 μg/mL for tetrahydrofuran(r=0.999 8),0.40-20.00 μg/mL for ethyl acetate(r=0.999 7), respectively. The limits of quantitation were 0.24, 0.40, 0.033, 0.40, 0.071, 0.058, 0.40 μg/mL,respectively. The limits of detection were 0.08,0.10,0.01,0.13,0.02,0.02,0.13 μg/mL,respectively. RSDs of precision,stability and reproducibility tests were all lower than 2%. The recoveries were 98.17%-100.48%(RSD=0.92%,n=9),97.77%-101.30%(RSD=1.32%,n=9),97.56%-100.85%(RSD=1.20%,n=9),98.64%-100.92%(RSD=0.87%,n=9),98.54%-100.62%(RSD=0.76%,n=9),98.26%-100.00%(RSD=0.74%,n=9),98.30%-100.59%(RSD=0.76%,n=9),respectively.CONCLUSIONS:The method has high sensitivity and good accuracy,and can be used for the simultaneous determination of residual methanol,ethanol,acetonitrile,isopropane,methylbenzene,tetrahydrofuran and ethyl acetate in Nilethylenol raw material.
OBJECTIVE:To establish a method for simultaneous determination of residual methanol,ethanol,acetonitrile,isopropanol,methylbenzene,tetrahydrofuran and ethyl acetate in Nilethylenol raw material. METHODS:GC was performed. The determination was performed on DB-WAX capillary column. The detector was hydrogen flame ionization detector with split ratio of5∶1. The carrier gas was nitrogen(purity:99.999%)at the flow rate of 1.0 mL/min. The sample size was 1 μL,directly sampling with bonded crosslinked polyethylene glycol as stationary phase. The initial temperature was 40 ℃ and was maintained for 5 min,increased to 90 ℃ at 10 ℃/min,and then increased to 200 ℃ at 5 ℃/min. The temperature of injector was 220 ℃,and detector temperature was 230 ℃. RESULTS:The linear range was 0.24-12.00 μg/mL for methanol(r=0.999 7),0.40-20.00 μg/mL for ethanol(r=0.999 5),0.033-1.64 μg/mL for acetonitrile(r=0.999 8),0.40-20.00 μg/mL for isopropanol(r=0.999 5),0.071-3.56 μg/mL for methylbenzene(r=0.999 6),0.058-2.88 μg/mL for tetrahydrofuran(r=0.999 8),0.40-20.00 μg/mL for ethyl acetate(r=0.999 7), respectively. The limits of quantitation were 0.24, 0.40, 0.033, 0.40, 0.071, 0.058, 0.40 μg/mL,respectively. The limits of detection were 0.08,0.10,0.01,0.13,0.02,0.02,0.13 μg/mL,respectively. RSDs of precision,stability and reproducibility tests were all lower than 2%. The recoveries were 98.17%-100.48%(RSD=0.92%,n=9),97.77%-101.30%(RSD=1.32%,n=9),97.56%-100.85%(RSD=1.20%,n=9),98.64%-100.92%(RSD=0.87%,n=9),98.54%-100.62%(RSD=0.76%,n=9),98.26%-100.00%(RSD=0.74%,n=9),98.30%-100.59%(RSD=0.76%,n=9),respectively.CONCLUSIONS:The method has high sensitivity and good accuracy,and can be used for the simultaneous determination of residual methanol,ethanol,acetonitrile,isopropane,methylbenzene,tetrahydrofuran and ethyl acetate in Nilethylenol raw material.
引文
[1]国家药典委员会.中华人民共和国药典:临床用药须知:化学药和生物制品卷[S].2015年版.北京:中国医药科技出版社,2015:554.
[2]王淑芳,刘晓阳.尼尔雌醇片溶出度测定方法的研究[J].药物分析杂志,2005,25(2):239-240.
[3]孙婷,张菁,刘云,等.反相高效液相色谱法测定尼尔雌醇原料及片剂的有关物质和含量[J].中国药业,2019,28(5):33-36.
[4]国家药典委员会.中华人民共和国药典:四部[S].2015年版.北京:中国医药科技出版社,2015:105-107.
[5]ICH指导委员会.药品注册的国际技术要求:质量部分[S].北京:人民卫生出版社,2006:79.
[6]吕东.化学药物残留溶剂研究的原则、方法及关注的问题[J].中国新药杂志,2008,17(20):1811-1813.
[7]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,2015:306.
[8]国家药典委员会.中国药典分析检测技术指南[S].北京:中国医药科技出版社,2017:224.
[9]关洪亮,潘祖亭.尼尔雌醇的荧光光谱法研究与应用[J].分析试验室,2006,25(1):20-23.
[10]刘英,刘葵葵,邓玉晓.顶空气相色谱法同时测定硫酸沃拉帕沙原料药中7种有机溶剂的残留量[J].中国药房,2018,29(16):2224-2227.
[11]汪斌,郑璐,姚仲青,等.顶空气相色谱法测定胡黄连苷Ⅱ原料药中7种有机溶剂残留量[J].中国药房,2015,26(27):3859-3861.
[12]吴朝华,王秀梅,顾保明,等.顶空毛细管气相色谱法测定盐酸丁卡因原料药中的残留溶剂[J].药物分析杂志,2011,31(6):1188-1192.
[13]张晶蓉.顶空气相色谱法测定富马酸喹硫平的残留溶剂[J].天津药学,2015,27(5):17-19.
[14]孙婷,张菁,刘云,等.HPLC法同时测定雌激素类药物尼尔雌醇片和己烯雌酚片中主药含量[J].中国药房,2019,30(4):469-472.
[15]张欣耘,李建华,杨永健,等.高效液相色谱法测定尼尔雌醇含量方法的建立[J].药物分析杂志,2001,21(2):105-107.
[2]王淑芳,刘晓阳.尼尔雌醇片溶出度测定方法的研究[J].药物分析杂志,2005,25(2):239-240.
[3]孙婷,张菁,刘云,等.反相高效液相色谱法测定尼尔雌醇原料及片剂的有关物质和含量[J].中国药业,2019,28(5):33-36.
[4]国家药典委员会.中华人民共和国药典:四部[S].2015年版.北京:中国医药科技出版社,2015:105-107.
[5]ICH指导委员会.药品注册的国际技术要求:质量部分[S].北京:人民卫生出版社,2006:79.
[6]吕东.化学药物残留溶剂研究的原则、方法及关注的问题[J].中国新药杂志,2008,17(20):1811-1813.
[7]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,2015:306.
[8]国家药典委员会.中国药典分析检测技术指南[S].北京:中国医药科技出版社,2017:224.
[9]关洪亮,潘祖亭.尼尔雌醇的荧光光谱法研究与应用[J].分析试验室,2006,25(1):20-23.
[10]刘英,刘葵葵,邓玉晓.顶空气相色谱法同时测定硫酸沃拉帕沙原料药中7种有机溶剂的残留量[J].中国药房,2018,29(16):2224-2227.
[11]汪斌,郑璐,姚仲青,等.顶空气相色谱法测定胡黄连苷Ⅱ原料药中7种有机溶剂残留量[J].中国药房,2015,26(27):3859-3861.
[12]吴朝华,王秀梅,顾保明,等.顶空毛细管气相色谱法测定盐酸丁卡因原料药中的残留溶剂[J].药物分析杂志,2011,31(6):1188-1192.
[13]张晶蓉.顶空气相色谱法测定富马酸喹硫平的残留溶剂[J].天津药学,2015,27(5):17-19.
[14]孙婷,张菁,刘云,等.HPLC法同时测定雌激素类药物尼尔雌醇片和己烯雌酚片中主药含量[J].中国药房,2019,30(4):469-472.
[15]张欣耘,李建华,杨永健,等.高效液相色谱法测定尼尔雌醇含量方法的建立[J].药物分析杂志,2001,21(2):105-107.