顶空毛细管气相色谱法测定阿托伐他汀钙原料药中残留溶剂的含量

目的：建立测定阿托伐他汀钙原料药中残留溶剂含量的方法。方法：采用顶空毛细管气相色谱法。色谱柱为DB-624毛细管柱，柱温采用程序升温（初始温度40℃，保持15mim，以10℃／min的速率升温至150℃，再以40℃／min的速率升温至250℃，保持5min），检测器为氢火焰离子化检测器，进样口温度为200℃，检测器温度为250℃，载气为氮气，流速为2．0ml／min，分流比为3：1，顶空温度为100℃，顶空时间为30min，顶空进样体积为1ml。结果：甲醇、乙醇、异丙醇、乙腈、甲基叔丁基醚、正己烷、乙酸乙酯、四氢呋喃、环己烷、正庚烷、甲苯检测质量浓度分别在23．702～142．212、38．44-230．64、42．26-253．56、4．814-28．884、41．148-246．888、2．976～17．856、42．53-255．18、7．016-42．096、33．484-200．904、40．54-243．24、7．75～46．5g／ml范围内与峰面积积分值呈良好的线性关系（r=0．9991、0．9998、0．9999、0．9954、0．9999、0．9994、0．9999、0．9999、0．9998、0．9998、0．9999）；精密度、稳定性、重复性试验的RSD≤2．89％；平均加样回收率分别为102．57％、99．59％、103．57％、102．62％、103．28％、101．48％、101．75％、101．85％、102．79％、104．11％、103．07％，RSD分别为2．39％、2．71％、2．44％、2．74％、2．31％、3．44％、4．64％、2．32％、2．82％、3．21％、2．57％（n=9）。结论：该方法专属性强、重复性好、结果可靠，适用于阿托伐他汀钙原料药中残留溶剂的含量测定。

Content Determination of Residual Solvent in Atorvastatin Calcium Raw Material by Headspace Capillary GC Method

OBJECTIVE： To establish a method for the content determination of residual solvents in Atorvastatin calcium raw material. METHODS： Headspace capillary GC method was adopted. The determination was performed on DB-624 capillary column at the rate of 2.0 ml/min using nitrogen gas as carrier gas and FID as the detector by temperature programming （initial column temperature of 40 ℃, maintaining for 15 rain, then raising to 150 ℃ at a rate of 10 ℃/min, and then raising to 250 ℃ at a rate of 40 ℃/min, maintaining for 5 min）. The split ratio was 3： 1, the temperature of the injector was maintaining at 200 ℃ and that of detector at 250 ℃. The equilibrium temperature was 100 ℃ and equilibrium time was 30 min. The volume of sample was 1 ml. RE- SULTS： The linear ranges were 23.702-142.212 μg/ml for methanol （r=0.999 1）, 38.44-230.64 μg/ml for ethanol （r=0.999 8）, 42.26-253.56 μg/ml for isopropanol （r=0.999 9）, 4.814-28.884 μg/ml for acetonitrile （r=0.995 4）, 41.148-246.888 μg/ml for methyl tert-butyl ether （r=0.999 9）, 2.976-17.856 μg/ml for n-hexane （r=0.999 4）, 42.53-255.18 μg/ml for ethyl acetate （r= 0.999 9）, 7.016-42.096 μg/ml for tetrahydrofuran （r=0.999 9）, 33.484-200.904 μ g/ml for cyclohexane （r=0.999 8）, 40.54-243.24 lag/ml for n-heptane （r=0.999 8）, 7.75-46.5 μg/ml for toluene （r=0.999 9）. RSDs of precision, stability and reproducibility tests were all lower than 2.89%. The average recoveries were 102.57% （RSD=2.39%, n=9）, 99.59% （RSD=2.71%, n=9）, 103.57% （RSD=2.44% ,n=9）, 102.62% （RSD=2.74% ,n=9）, 103.28% （RSD=2.31% ,n=9）, 101.48% （RSD=3.44%, n=9）, 101.75%（RSD=4.64%,n=9）, 101.85%（RSD=2.32%,n=9）, 102.79%（RSD=2.82%,n=9）, 104.11%（RSD=3.21%, n=9）, 103.07% （RSD=2.57%, n=9）, respectively. CONCLUSIONS： The method is specific, repeatable, reliable and suitable for the content determination of residual solvents in Atorvastatin calcium raw material.