反相离子对色谱法测定替卡西林钠中的有关物质的含量

Determination of related substance in ticarcillin by RPIC

目的建立反相离子对色谱法测定替卡西林钠中的有关物质的含量。方法色谱柱为Chromegabond TMS C_1(150 mm×4.6 mm,5μm)柱;流动相A为乙腈-磷酸盐缓冲液(含浓度5mmol·L^(-1)四丁基溴化铵的20mmol·L^(-1)的磷酸二氢钠溶液,用磷酸调节pH值至3.0,体积比1∶4),流动相B为乙腈-磷酸盐缓冲液(含5mmol·L^(-1)四丁基溴化铵的20mmol·L^(-1)的磷酸二氢钠溶液,用磷酸调节pH值至3.0,体积比1∶1),梯度洗脱;流速为1.5 mL·min^(-1);检测波长为230nm;柱温为30℃。结果破坏试验结果显示,本方法能够将主峰和杂质峰完全分离;精密度RSD为0.36%;替卡西林杂质A重复性、中间精密度RSD为0.19%、0.33%,替卡西林杂质D重复性、中间精密度RSD为0.94%、1.14%,最大杂质重复性、中间精密度RSD为1.03%、0.95%,总杂质的重复性、中间精密度RSD为0.86%、1.27%;在4℃条件下存放,12h内溶液稳定;替卡西林的质量浓度在10.116~101.16mg·L^(-1)内与峰面积呈良好的线性关系(r>0.999 9,n=5);检测限质量浓度为0.105mg·L^(-1),定量限质量浓度为0.260mg·L^(-1)。结论该方法可用于替卡西林钠的质量控制。

Objective To establish a method for the determination of related substance in sodium ticarcillin by RPIC. Methods Chromegabond TMS C1 （ 150 mm×4.6mm,5μm） column was used, the mobile phases were mobile phase A： Acetonitrile-buffer （20 mmol·L^-1 sodium dihydrogen phosphate solution containing 5 mmol·L^-1 tetrabutylammonium bromide） （1：4, V： V）and the pH was adjusted to 3.0 with phosphoric acid, and mobile phase B： Acetonitrile-buffer （20 mmol·L^-1 sodium dihydrogen phosphate solution containing 5 mmol·L^-1 tetrabutylammonium bromide） （1：1, V： V）and the pH was adjusted to 3.0 with phosphoric acid. Gradient elution was used. The flow rate was 1.5 mL·min·m^-1 with detection wavelength of 230 nm. Column temperature was 30℃. Results Forced degradation experiment showed that this chromatographic condition could completely separate the main peak from impurity peaks with good system precision（ RSD = 0.36% ）, good repeatability and good intermediate precision. The RSD of impurity A was 0.19% and 0.33% ,the RSD of impurity D was 0.94% and 1.14% ,the RSD of major impurity was 1.03% and 0.95% ,the RSD of total impurities was 0.86% and 1.27%. The solution of ticarcillin disodium could be stable for 12 hours under the condition of 4℃. The linear range was 10. 116 - 101. 16 mg·L^-1 （ r 〉 0. 999 9 ,n =5）. The limit of detection was 0. 105 mg·L^-1 and limit of quantification concentration was 0. 260 mg·L^-1. Conclusions The method was specific, sensitive, reproducible, accurate and reliable. It can be used for quality control of sodium ticarcillin.