顶空气相色谱法测定对氯苯氧异丁酸甲氧基苯丙烯酸酯原料药中5种有机溶剂的残留量

Determination of Five Organic Solvent Residues in p-Chlorophenoxyisobutyric Acid Methoxyphenyl Acrylate by Head Space Gas Chromatography

目的建立顶空气相色谱法测定对氯苯氧异丁酸甲氧基苯丙烯酸酯原料药中乙醇、丙酮、三氯甲烷、吡啶和甲苯有机残留溶剂的方法。方法采用检测器为氢火焰离子化检测器(FID),色谱柱为Agilent DB-624毛细管柱(30 m×0.32 mm,1.8?m),溶剂为DMSO,进样口温度为200℃,检测器温度250℃,分流比为10︰1,程序升温,N2为载气,H2和空气为燃气,顶空平衡温度85℃,平衡时间30 min,进样体积1μL。结果乙醇、丙酮、三氯甲烷、吡啶和甲苯在建立的色谱条件下均能完全分离,分离度均>1.5,理论板数均>10 000;在考察浓度范围内线性关系良好(相关系数r分别为0.999 8,0.999 8,0.999 7,0.999 6,0.999 4);定量限分别为19.83,4.50,48.28,10.44,2.08μg·m L-1;检测限分别为3.97,0.90,9.66,3.07,0.69μg·m L-1;重复性RSD均<2.5%;平均回收率为102.40%~106.45%;对照品溶液在24 h内稳定性良好。结论该方法操作简便、灵敏,结果准确、可靠,可用于对氯苯氧异丁酸甲氧基苯丙烯酸酯原料药中有机溶剂残留量的控制。

OBJECTIVE To establish a head space gas chromatography method for determination of ethanol, acetone, chloroform, pyridine and toluene residual solvents in active pharmaceutical ingredients of p-chlorophenoxyisobutyric acid methoxyphenyl acrylate. METHODS The experiment was carried out by headspace gas chromatography with a detector for the hydrogen flame ionization detector（FID） and the column for the Agilent DB-624 capillary column（30 m×0.32 mm, 1.8 μm）. The sample was dissolved in DMSO solvent. The temperature of inlet was 200 and the temperature ℃of detector was 250 ℃. The split ratio was set to 10︰1. Program temperature was used in the whole process, and the N2 was used as carrier gas, H2 and air were used as burn gas. The headspace balance temperature was 85 ℃, and the balance time was 30 min. In such conditions, the sample was injected 1 μL each time. RESULTS Ethanol, acetone, chloroform, pyridine and toluene could be completely separated in the established method, R were all 〉1.5, N were all 〉10 000; the linear relationship was good in the investigated mass concentration degree（r was 0.999 8, 0.999 8, 0.999 7, 0.999 6, 0.999 4）; the limit of quantification was 19.83, 4.50, 48.28, 10.44, 2.08 μg·m L-1, respectively; limit of detection was 3.97, 0.90, 9.66, 3.07, 0.69 μg·m L-1 respectively; RSD were all 〈2.5%; the average recoveries were within 102.40%-106.45%; the reference substance kept stable within 24 h. CONCLUSION The method is simple, sensitive, with accurate and reliable results, which can be applied on the organic solvent residue control of p-chlorophenoxyisobutyric acid methoxyphenyl acrylate.