顶空气相色谱法同时测定新药CBT108中12种残留溶剂

Simultaneous Determination of Twelve Kinds of Residual Solvents in A New Drug CBT108 By Headspace Gas Chromatography

采用顶空气相色谱技术,建立了同时测定新药CBT108中12种残留溶剂的方法。优化了平衡加热时间和程序升温时间以及制样的溶剂,并通过验证确定了本方法的合理性、准确性和可行性。在优化的实验条件下,采用DB-624型毛细管柱(6%氰丙基苯基-94%二甲基聚硅氧烷为固定液,30 m×0.53 mm×3.0μm)分离、氢火焰离子化检测器检测、内标法定量的分析方案,实现了甲醇、乙醇、乙醚、丙酮、乙腈、二氯甲烷、正己烷、乙酸乙酯、四氢呋喃、庚烷、甲苯和四氯化碳共12种残留溶剂的同时分离与测定。12种溶剂在各自的范围内线性关系良好,线性相关系数(R^2)均>0.997;以10倍信噪比确定方法定量限,以3倍信噪比确定方法检出限,分别为:甲醇0.024μg/mL、0.0072μg/mL;乙醇0.1μg/mL、0.012μg/mL;乙醚0.01μg/mL、0.005μg/mL;丙酮0.1μg/mL、0.008μg/mL;乙腈1.025μg/mL、0.0615μg/mL;二氯甲烷0.09μg/mL、0.06μg/mL;正己烷0.0174μg/mL、0.0145μg/mL;乙酸乙酯0.25μg/mL、0.008μg/mL;四氢呋喃0.108μg/mL、0.014μg/mL;四氯化碳0.16μg/mL、0.0004μg/mL;庚烷0.0075μg/mL、0.005μg/mL;甲苯0.0445μg/mL、0.0014μg/mL。在3个添加水平下,12种残留溶剂的加标回收率在90.96%~108.67%之间,相对标准偏差为0.1%~5.7%。结果表明,本法简单、快速、重现性好、准确性高,可用于实际药品中以上12种残留溶剂的检测,并可对其它药物中残留溶剂的检测提供参考。

A simple and sensitive method for simultaneous determination of 12 kinds of residual solvents in a new drug CBT108 was established and validated by headspace gas chromatographic technology.The rationality,accuracy and feasibility of the analytical method were verified.Under the optimized conditions,simultaneous separation and determination of 12 kinds of residual solvents,including methanol,ethanol,ether,acetone,acetonitrile,dichloromethane,n-hexane,ethyl acetate,tetrahydrofuran,heptane,toluene and carbon tetrachloride was carried out by using a DB624 capillary column(30 m×0.53 mm×3.0μm)for separation,a flame ionization detector for detection and internal standard method for quantitation.Good linearity was obtained for 12 solvents with the correlation coefficients(R 2)of more than 0.997.The limits of quantitation and detection were defined at S/N=3 and S/N=10,respectively.LOQ and LOD for 12 solvents were given as 0.024μg/mL and 0.0072μg/mL for methanol,0.1μg/mL and 0.012μg/mL for ethanol,0.01μg/mL and 0.005μg/mL for ether,0.1μg/mL and 0.008μg/mL for acetone,1.025μg/mL and 0.0615μg/mL for acetonitrile,0.09μg/mL and 0.06μg/mL for dichloromethane,0.09μg/mL and 0.06μg/mL for n-hexane,0.25μg/mL and 0.008μg/mL for ethyl acetate,0.108μg/mL and 0.014μg/mL for tetrahydrofuran,0.16μg/mL and 0.0004μg/mL for carbon tetrachloride,0.0075μg/mL and 0.005μg/mL for heptane,and 0.0445μg/mL and 0.0014μg/mL for toluene.The adding standards recoveries for 12 residual solvents at three spiked levels were in the range of 90.96%-108.67%,with relative standard deviations of 0.1%-5.7%.This simple,high accuracy and good repeatability method is feasible for rapidly determination of 12 residual solvents in drug candidate CBT108.Meanwhile,this simple method provides a consulted value for detection of residual solvents in other medicines.