摘要
目的：建立甲啶铂高效液相色谱分析方法,采用该方法测定甲啶铂原料药的纯度,并研究甲啶铂在酸碱、氧化还原环境中的稳定性。方法：采用Waters XTerra PR C18（250 mm×4.6 mm,5μm）色谱柱,以15%乙腈水溶液为流动相等度洗脱,流速1.0 mL·min^-1,二极管阵列检测器（PDA）于200～400 nm内检测含量并分析纯度。在甲啶铂溶液中添加HCl、Na OH、H2O2和Na HSO3,采用高效液相色谱法测定含量,考察甲啶铂在酸碱、氧化还原环境中的稳定性。结果：此方法可以快速灵敏地测定甲啶铂含量,甲啶铂质量浓度在0.02～0.2 mg·mL^-1范围内线性相关（R^2〉0.999 9）,检测限和定量限分别为0.094 ng和0.22ng。此方法可以同时将甲啶铂与顺铂、三氯氨铂酸钾和顺式-二氯-氨、（3-甲基吡啶）合铂（Ⅱ）等杂质有效分离。纯度分析表明,试制的3批甲啶铂原料药纯度高。稳定性试验显示,碱性及氧化环境对甲啶铂具有很强的破坏作用。结论：此方法可用于甲啶铂原料药及其制备过程中的检测和监控,在甲啶铂原料药保存和制剂研究过程中应避免与碱性和氧化性物质接触。
Objective： To develop a new HPLC method for an easy and rapid determination of picoplatin,and investigate its purity and its stability in acid,alkaline,oxidative and reductive conditions through this method.Methods： The Waters XTerra PR C18（ 250 mm × 4. 6 mm,5 μm） column was used with a water solution of 15%acetonitrile as the mobile phase,and the photo-diode array detector was used to detect and analyze the purity between 200 nm and 400 nm. The stability of picoplatin in acid,alkaline,oxidative and reductive conditions was investigated by the addition of HCl,Na OH,H2O2 and Na HSO3 into the solution and HPLC was used for content determination. Results： This method could rapidly and sensitively determine picoplatin content. The calibration curve was linear within the concentration range of 0. 02-0. 2 mg·mL^-1（ R^2= 0. 999 9）. The limit of detection was 0. 094 ng and limit of quantification was 0. 022 ng. The method can separate picoplatin from cisplatin,potassium trichloroammine platinate and cis-amminedichloro（ 3-methylpyridine） platinum effectively. The purity analysis indicated that picoplatin（ API） had high purity in the three batches of test preparations. And the stability test revealed that picoplatin was unstable in alkaline and oxidative conditions. Conclusion： The developed method is suitable for the content determination of picoplatin and its test and monitoring during the preparation process. And picoplatin should be avoided contacting with alkaline and oxidizing substances during storing and studying of preparation.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2015年第2期306-310,共5页
Chinese Journal of Pharmaceutical Analysis
基金
云南省科技厅重点新产品开发计划“抗肿瘤化学Ⅰ类新药甲啶铂注射液的临床前预研究”(2013BC010)
