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
王茉莉,宋更申,庞文哲,张兰桐
WANG Mo-li,SONG Geng-shen,PANG Wen-zhe,ZHANG Lan-tong
摘要(Abstract)：
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 C_1(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 to3.0with 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 3.0with phosphoric acid.Gradient elution was used.The flow rate was 1.5 mL·min~(-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 was0.94%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.
关键词(KeyWords)：
替卡西林钠;反相离子对色谱法;有关物质;测定
trcillin sodium;reversed phase ion pair chromatography;reated substance;dtermination
基金项目(Foundation):
作者(Author):
王茉莉,宋更申,庞文哲,张兰桐
WANG Mo-li,SONG Geng-shen,PANG Wen-zhe,ZHANG Lan-tong
DOI: 10.14066/j.cnki.cn21-1349/r.2017.06.010
参考文献(References)：
- [1]欧贝丽,姜立群,章宇.β-内酰胺类抗生素药物的杂质分析及其质量研究[J].分析实验室,2007,26(10):166-167.
- [2]蒋煜,张哲峰,王虹.β-内酰胺类抗生素异构体杂质研究和质控进展[J].中国抗生素杂志,2010,35(8):561-566.
- [3]代丽萍,胡林.HPLC法测定磺苄西林钠中的有关物质[J].中国抗生素杂志,2008,33(4):212-222.
- [4]张冠柱,李京喜.HPLC法测定替卡西林钠的含量及有关物质[J].齐鲁药事,2005,24(2):95-96.
- [5]陈悦.HPLC离子对梯度洗脱法同时测定阿莫西林钠/氟氯西林钠的含量和有关物质[J].中国抗生素杂志,2004,29(1):15-18.
- [6]陈汝红.梯度洗脱HPLC法测定苄星青霉素中的有关物质[J].中国抗生素杂志,2012,37(3):223-226.
- [7]王明娟,王晨,王立新,等.青霉素V钾及其有关物质分析方法的比较[J].药物分析杂志,2008,28(9):1515-1520.
- [8]熊雯,张丹.对USP与BP替卡西林HPLC方法分离替卡西林差向异构体的比较[J].中国抗生素杂志,2010,35(2):102-104.
- [9]周晓溪,郭景文,郑台,等.国产注射用氨苄西林钠杂质谱与其生产工艺的相关性研究[J].药物分析杂志,2013,33(3):486-489.
- [10]张志斌,钱卫德,杭亚军,等.反相离子对色谱法测定鱼腥草素钠的含量[J].中成药,2006,28(6):895-896.
- [11]骆雪芳,尹小英,付静静,等.柱温和流速对反相离子对色谱法分析寡核苷酸的影响[J].分析化学,2008,36(5):627-631.