论文部分内容阅读
目的:建立气相色谱法同时测定复方庚酸炔诺酮注射液中苯甲醇与苯甲醛的含量,以控制复方庚酸炔诺酮注射液的质量。方法:采用毛细管柱气相色谱法,用聚乙二醇毛细管色谱柱(DB-WAX,30 m×0.53 mm,1.0μm),进样口温度为200℃,分流比为10∶1,恒压模式,柱压保持在34.5 kPa,初始柱温为50℃,以每分钟5℃的升温速率升至220℃,保持15min,载气为氦气,以FID为检测器,检测器温度为300℃,进样量为1μL。结果:苯甲醇在0.032～40.13 mg.mL-1范围内峰面积与浓度的线性关系良好,r为1.0000(n=7),高、中、低平均加样回收率分别为94.3%、94.3%、94.9%,RSD分别为0.9%、0.7%、2.6%(n=3);苯甲醛在0.001～0.7 mg.mL-1的范围内峰面积与浓度的线性关系良好,r为0.99999(n=7),高、中、低平均加样回收率分别为95.9%、96.4%、99.8%,RSD分别为0.6%、1.2%、3.3%(n=3)。苯甲醇的高、中、低浓度的日间精密度的RSD分别为0.8%、1.1%、1.7%(n=3);苯甲醛的高、中、低浓度的日间精密度的RSD分别为0.7%、0.9%、3.4%(n=3)。苯甲醇与苯甲醛定量限分别为1.9 ng(RSD=2.5%,n=10)和2.3 ng(RSD=4.6%,n=10),检测限分别为0.58 ng和0.69 ng;对照品溶液在96h内保持稳定。测定了4批不同批号的样品,结果苯甲醇的含量比较稳定,分别为1.97%、1.97%、2.02%和2.04%,与处方投样量(2%)保持一致,苯甲醛的含量因生产日期不同有很大的差异,分别为0.09%、0.08%(均为2008年生产)、0.01%、0.01%(均为2010年生产)。根据处方,苯甲醛主要由苯甲醇氧化而得,将结果折算成以样品中苯甲醇的量计,含苯甲醛分别为4.7%、4.3%、0.5%和0.4%。结论:本法操作简单,结果准确,专属性好,可用作控制复方庚酸炔诺酮注射液中苯甲醇的含量,同时可监测该制剂中苯甲醛的量的变化。在复方庚酸炔诺酮注射液贮存过程中,苯甲醛含量随贮存时间不断增加,可能会产生与苯甲醛相关的不良反应,应该纳入到监管检测的范围里来。而其他含苯甲醇的注射液中苯甲醛是否过量也应受到重视和研究。
OBJECTIVE: To establish a gas chromatographic method for the simultaneous determination of benzyl alcohol and benzaldehyde in norethindrone norethindrone injection to control the quality of norethindrone injection. Methods: The capillary column gas chromatography was used. The injection temperature was 200 ℃ with a polyethylene glycol capillary column (DB-WAX, 30 m × 0.53 mm, 1.0 μm) , The column pressure was kept at 34.5 kPa and the initial column temperature was 50 ° C. The temperature was raised to 220 ° C at a rate of 5 ° C per minute for 15 minutes. The carrier gas was helium. The detector temperature was 300 ° C using a FID detector. Injection volume of 1μL. Results: The linear relationship between the peak area and the concentration of benzyl alcohol in the range of 0.032-40.13 mg · mL-1 was r = 1.0000 (n = 7), and the average recoveries were 94.3%, 94.3% , 94.9% with RSD of 0.9%, 0.7% and 2.6% respectively (n = 3). The linear relationship between peak area and concentration of benzaldehyde in the range of 0.001-0.7 mg.mL-1 was good with r of 0.99999 (n = 7). The mean recoveries of high, medium and low were 95.9%, 96.4% and 99.8%, respectively, with RSDs of 0.6%, 1.2% and 3.3%, respectively. The RSDs of daytime precision for high, medium and low concentrations of benzyl alcohol were 0.8%, 1.1% and 1.7%, respectively (n = 3). The RSDs of daytime precision of benzaldehyde at high, medium and low concentrations were 0.7%, 0.9%, 3.4% (n = 3). The limit of quantification (RSD) was 2.5 ng (n = 10) and 2.3 ng (RSD = 4.6%, n = 10) with limit of detection of 0.58 ng and 0.69 ng for benzyl alcohol and benzaldehyde respectively. Stable within. The results showed that the contents of benzyl alcohol were stable at 1.97%, 1.97%, 2.02% and 2.04%, respectively, which were consistent with the dosage of 2% The difference is very different, respectively 0.09%, 0.08% (both in 2008 production), 0.01%, 0.01% (all 2010 production). According to the prescription, benzaldehyde is mainly obtained from the oxidation of benzyl alcohol, and the result is converted into 4.7%, 4.3%, 0.5% and 0.4% of benzaldehyde in the sample based on the amount of benzyl alcohol in the sample. Conclusion: The method is simple, accurate and specific. It can be used to control the content of benzyl alcohol in norethindrone nheptanetetrazole injection and to monitor the change of the amount of benzaldehyde in the preparation. During the storage of norethisterone heptanoate injection, the increase of benzaldehyde content with storage time may cause side effects related to benzaldehyde, which should be included in the scope of regulatory testing. And other benzyl alcohol injection benzaldehyde in excess should also be paid attention to and research.