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高效液相色谱法测定地拉罗司有关物质的分析方法研究
高效液相色谱法测定地拉罗司有关物质的分析方法研究
丁文宇,唐克慧,王宇驰,张春然,张静霞,李喆宇,邓思思

成都大学四川抗菌素工业研究所,成都 610052
An HPLC analytical method for determining related substances in deferasirox
(Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, China)

摘要参考文献相关文章

起始页:2376

摘要:目的:研究建立高效液相色谱法(high performance liquid chromatography, HPLC)测定地拉罗司有关物质的方法。方法:采用CAPCELL PAK C18 MGⅡ色谱柱(250 mm×4.6 mm,5 μm),以0.05 mol·L-1磷酸二氢钠溶液(磷酸调至pH 3.5)为流动相A、乙腈为流动相B进行梯度洗脱,检测波长为245 nm,流速为1.0 mL·min-1。结果:地拉罗司与原料、中间体及其他杂质峰分离良好;地拉罗司的线性范围为0.1~40 μg·mL-1(R2=0.999 9,n=9),水杨酸溶液的线性范围为0.2~80 μg·mL-1(R2=0.999 9,n=6),水杨酸酰胺溶液的线性范围为0.1~40 μg·mL-1(R2=0.999 7,n=6),中间体的线性范围为0.1~50 μg·mL-1(R2=0.999 9,n=7);精密度良好,地拉罗司0.1%自身对照溶液重复进样的RSD值为0.35%;分别以水杨酸、水杨酸酰胺和中间体进行回收率试验,平均回收率分别为99.83%(RSD=1.68%),98.26%(RSD=1.47%)和99.24%(RSD=1.58%);分别按杂质对照品外标法和主成分自身对照法计算杂质含量,3批样品最大单个杂质均不超过0.07%,总杂质含量不超过0.23%。结论:本方法准确、灵敏、专属性强,能有效地测定地拉罗司中的有关物质。

关键词:地拉罗司;有关物质;RP-HPLC;梯度洗脱

通讯作者:唐克慧,女,研究员,主要从事药物质量控制和杂质研究。

基金项目:

作者简介:丁文宇,女,硕士研究生,主要从事质量控制与杂质研究。

Abstract:Objective: To establish a high performance liquid chromatography (HPLC) method for the determination of related substances in deferasirox. Methods: The separation was performed on the CAPCELL PAK C18 MGⅡ column (250 mm×4.6 mm, 5 μm) with a gradient elution, the mobile phase was consisted of phosphate buffer solution (0.05 mol·L-1 dipotassium phosphate solution, adjusted to pH 3.5 by phosphoric acid)-acetonitrile. The detection wavelength was set at 245 nm, and the flow rate was 1.0 mL·min-1. Results: The main peak was well separated from the peaks of raw materials and intermediate as well as other impurity peaks. The linearity range of deferasirox was 0.1~40 μg·mL-1 (R2=0.999 9, n=9), the linearity ranges of salicylic acid and salicylamide were 0.2~80 μg·mL-1 (R2=0.999 9, n=6) and 0.1~40 μg·mL-1 (R2=0.999 7, n=6), and the linearity range of intermediate was 0.1~50 μg·mL-1 (R2=0.999 9, n=7). The precision was good, and RSD of duplicate deferasirox measeurements was 0.35%. Average recovery of salicylic acid, salicylamide and intermediate were 99.83% (RSD=1.68%), 98.26% (RSD=1.47%) and 99.24% (RSD=1.58%). Determined by external standard method and the main component self-comparison method, the content of individual impurity in deferasirox was lower than 0.07%, and that of total impurities was lower than 0.23%. Conclusion: The method was accurate, sensitive and specific, thus it is suitable for the determination of related substances in deferasirox.

Key words:deferasirox; related substances; RP-HPLC; gradient elution

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