顶空气相色谱法同时测定保泰松原料药中6种溶剂残留量
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摘要
目的:建立同时测定保泰松原料药中6种溶剂残留量的方法。方法:采用顶空气相色谱法。色谱柱为Agilent HP-5毛细管柱,程序升温,进样口温度为200℃,检测器为氢火焰离子化检测器,温度为250℃,载气为氮气(纯度:99.99%),载气流速为2.0 mL/min,分流比为5∶1,顶空平衡温度为60℃,顶空平衡时间为30 min,顶空进样量为1 mL。结果:甲醇、乙醇、异丙醇、二氯甲烷、乙酸乙酯和N,N-二甲基甲酰胺检测质量浓度线性范围分别为0.15～4.5μg/mL(r=0. 999 9)、0.25～7.5μg/m L(r=0. 999 7)、0.25～7.5μg/mL(r=0. 999 7)、0.03～0.9μg/m L(r=0. 999 3)、0.25～7.5μg/mL(r=0. 999 3)、0.044～1.32μg/mL(r=0. 999 3);检测限分别为0.05、0.08、0.08、0.01、0.08、0.015μg/mL,定量限分别为0.15、0.25、0.25、0.03、0.25、0.044μg/mL;精密度试验的RSD<2.0%,稳定性、重复性试验的RSD<3.0%;加样回收率分别为98.75%～100.12%(RSD=0.56%,n=9)、98.07%～101.20%(RSD=1.12%,n=9)、98.36%～100.80%(RSD=0.92%,n=9)、98.33%～101.67%(RSD=0.98%,n=9)、98.11%～100.40%(RSD=0.72%,n=9)、98.75%～101.05%(RSD=0.89%,n=9)。结论:该方法操作简便、准确,精密度、稳定性、重复性、耐用性好,可用于保泰松原料药中6种溶剂残留量的同时测定。
OBJECTIVE:To establish a method for simultaneous determination of residual solvents in phenylbutazone raw material. METHODS:Head-space GC was adopted. The determination was performed on Agilent HP-5 capillary column by temperature programming. The temperature of injector was 200 ℃,and detector was flame ionization detector with temperature of250 ℃;carrier gas was nitrogen(purity:99.99%)at the flow rate of 2.0 mL/min. The split ratio was 5 ∶1. Headspace equilibrium temperature was 60 ℃,and equilibration time was 30 min. The sample size was 1 mL. RESULTS:The linear range was 0.15-4.5μg/mL for methanol(r=0.999 9),0.25-7.5 μg/mL for ethanol(r=0.999 7),0.25-7.5 μg/mL for isopropyl alcohol(r=0.999 7),0.03-0.9 μ g/mL for dichloromethane(r=0.999 3),0.25-7.5 μ g/m L for ethyl acetate(r=0.999 3),0.044-1.32 μ g/m L for N,N-dimethyl formamide(r=0.999 3),respectively. The limits of detection were 0.05,0.08,0.08,0.01,0.08,0.015 μg/m L. The limits of quantitation were 0.15,0.25,0.25,0.03,0.25,0.044 μ g/mL. RSDs of precision test were lower than 2.0%. RSDs of stability and reproducibility tests were lower than 3.0%. The recoveries were 98.75%-100.12%(RSD=0.56%, n=9),98.07%-101.20%(RSD=1.12%,n=9),98.36%-100.80%(RSD=0.92%,n=9),98.33%-101.67%(RSD=0.98%,n=9),98.11%-100.40%(RSD=0.72%,n=9)and 98.75%-101.05%(RSD=0.89%,n=9). CONCLUSIONS:The method is simple,accurate,precise,stable,reproducible and durable,and can be used for simultaneous determination of 6 residual solvents in phenylbutazone raw material.
OBJECTIVE:To establish a method for simultaneous determination of residual solvents in phenylbutazone raw material. METHODS:Head-space GC was adopted. The determination was performed on Agilent HP-5 capillary column by temperature programming. The temperature of injector was 200 ℃,and detector was flame ionization detector with temperature of250 ℃;carrier gas was nitrogen(purity:99.99%)at the flow rate of 2.0 mL/min. The split ratio was 5 ∶1. Headspace equilibrium temperature was 60 ℃,and equilibration time was 30 min. The sample size was 1 mL. RESULTS:The linear range was 0.15-4.5μg/mL for methanol(r=0.999 9),0.25-7.5 μg/mL for ethanol(r=0.999 7),0.25-7.5 μg/mL for isopropyl alcohol(r=0.999 7),0.03-0.9 μ g/mL for dichloromethane(r=0.999 3),0.25-7.5 μ g/m L for ethyl acetate(r=0.999 3),0.044-1.32 μ g/m L for N,N-dimethyl formamide(r=0.999 3),respectively. The limits of detection were 0.05,0.08,0.08,0.01,0.08,0.015 μg/m L. The limits of quantitation were 0.15,0.25,0.25,0.03,0.25,0.044 μ g/mL. RSDs of precision test were lower than 2.0%. RSDs of stability and reproducibility tests were lower than 3.0%. The recoveries were 98.75%-100.12%(RSD=0.56%, n=9),98.07%-101.20%(RSD=1.12%,n=9),98.36%-100.80%(RSD=0.92%,n=9),98.33%-101.67%(RSD=0.98%,n=9),98.11%-100.40%(RSD=0.72%,n=9)and 98.75%-101.05%(RSD=0.89%,n=9). CONCLUSIONS:The method is simple,accurate,precise,stable,reproducible and durable,and can be used for simultaneous determination of 6 residual solvents in phenylbutazone raw material.
引文
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[8]刘葵葵,邓玉晓,邢学敏,等.顶空气相色谱法同时测定法匹拉韦原料药中5种有机溶剂的残留量[J].中国药房,2017,28(24):3415-3418.
[9]孙悦,王卫,唐素芳.顶空气相色谱法测定盐酸帕罗西汀中残留的有机溶剂及基质效应考察[J].药物分析杂志,2010,30(5):963-967.
[10]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.
[11]吴朝华,王秀梅,顾保明.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.
[12]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.
[2]闫丽,岳崇兵,李厚明.保泰松的合成工艺研究[J].市场调研,2015,1(1):11-12.
[3]曹琳琳.保泰松的合成新工艺及其衍生物的合成研究[D].郑州:郑州大学,2007.
[4]姜建国,孙婷,郭永辉,等.顶空气相色谱法同时测定比沙可啶原料药中2种溶剂残留量[J].中国药房,2016,27(30):4297-4299.
[5]中华人民共和国卫生部药典委员会.中华人民共和国卫生部药品标准:二部:五册[S].1996:64-65.
[6]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,2017:410.
[7]李眉,马玉楠.简介ICH关于药品中溶剂残留的指导原则[J].中国药师,1998,1(3):119-120.
[8]刘葵葵,邓玉晓,邢学敏,等.顶空气相色谱法同时测定法匹拉韦原料药中5种有机溶剂的残留量[J].中国药房,2017,28(24):3415-3418.
[9]孙悦,王卫,唐素芳.顶空气相色谱法测定盐酸帕罗西汀中残留的有机溶剂及基质效应考察[J].药物分析杂志,2010,30(5):963-967.
[10]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.
[11]吴朝华,王秀梅,顾保明.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.
[12]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.