顶空采样-毛细管气相色谱法分析格列美脲原料药中的溶剂残留

建立了顶空采样-毛细管气相色谱检测格列美脲原料药中溶剂残留的分析方法。对产自国内8个生产厂家的格列美脲样品中有机溶剂的残留状况进行了系统评价,结合药品生产工艺信息,确定了丙酮、乙酸乙酯、甲醇、异丙醇、乙醇、氯仿、甲苯、1,4-二氧六环、吡啶、氯苯、乙醚、二氯甲烷、正己烷和苯等14种有机溶剂为残留检测对象。根据被测组分在色谱柱上的保留性质将其分为两类,以实现基线分离。用Supelco-Wax极性色谱柱,以乙腈为内标物,分离检测了丙酮、乙酸乙酯、甲醇、异丙醇、乙醇、氯仿、甲苯、1,4-二氧六环、吡啶和氯苯的残留量;用Supelco OVI-G43弱极性色谱柱,以丁酮为内标,分离检测了乙醚、二氯甲烷、正己烷和苯的残留量。14种残留组分在各自的浓度范围内呈良好的线性关系(r=0.99167～0.99997,n=8),最低检出限范围为0.2～13.5 μg/g;14种残留组分检测的日间重复性(以相对标准偏差(RSD)计)为0.6%～9.2%(n=3),3种加标浓度的平均添加回收率为86.3%～104.1%(RSD为0.2%～5.3%,n=16)。实验结果表明,该方法简单、灵敏、可靠,适用于格列美脲中残留溶剂的分析确证。

Analysis of solvent residues in raw material drug of glimepiride by head-space sampling-capillary gas chromatography

An analytical method for the solvent residues in the raw material drug of glimepiride has been established by head-space sampling capillary gas chromatography. General evaluation was made for the distribution of organic residual solvents in glimepiride samples from 8 differ-ent domestic manufacturers. Based on the evaluation-test results and the information provided by manufacturers, 14 target solvents were ascertained including acetone, ethyl acetate, metha-nol, isopropanol, ethanol, chloroform, toluene, 1,4-dioxane, pyridine, chlorobenzene, ether, dichloromethane, n-hexane and benzene. The target solvents were divided into two groups for baseline separation according to their column-retention specificity. Acetone, ethyl acetate, methanol, isopropanol, ethanol, chloroform, toluene, 1,4-dioxane, pyridine and chloroben-zene were separated on a Supelco-Wax capillary column with acetonitrile as internal standard, while ether, dichloromethane, n-hexane and benzene were determined on a Supelco OVI-G43 capillary column with butanone as internal standard. Linear responses were obtained for the 14 residual solvents in their respective concentration ranges (r = 0. 991 67 - 0. 999 97 , n = 8), and the limits of detection were 0. 2-13. 5 μg/g. The inter-day reproducibilities, measured as rela-tive standard deviations (RSDs), were 0. 6%-9. 2% (n = 3). The average recoveries of three concentration levels were 86. 3%-104. 1% with the RSD of 0. 2% -5. 3% (N = 16). The devel-oped method is simple, sensitive, and accurate for the residual solvent analysis in glimepiride samples.