目的: 建立同时控制注射用头孢米诺钠中有关物质和聚合物杂质的杂质分析方法。方法: 以注射用头孢米诺钠高温破坏溶液为降解溶液,采用Kromisil C18（250 mm×4.6 mm,5 μm）色谱柱,以10 mmol · L-1磷酸盐缓冲溶液（pH 2.0）-乙腈（96∶4）为流动相A,以乙腈为流动相B,进行梯度洗脱,流速1.0 mL · min-1,柱温25 ℃,检测波长254 nm,进样体积20 μL,建立注射用头孢米诺钠杂质分析的反相高效液相色谱（RP-HPLC）法,采用二维液质联用（2D HPLC-MS/MS）法对其进行专属性研究和杂质结构推断。结果: 在注射用头孢米诺钠降解溶液中推定了14个主要杂质,其中首次鉴定到3个头孢米诺二聚体。采用加校正因子的主成分自身对照法,测得7批注射用头孢米诺钠中杂质3的含量为0.01%~0.13%;杂质4的含量为0.10%~0.16%;杂质5的含量为0.02%~0.07%;杂质6的含量为0.04%~0.07%;聚合物杂质的含量为0.03%~0.06%;其他最大单个杂质的含量为0.01%~0.03%;总杂质含量为0.28%~0.63%。结论: 可将头孢米诺钠高温破坏溶液作为有关物质和聚合物杂质系统适用性溶液,建立的RP-HPLC法可同时控制注射用头孢米诺钠中有关物质杂质和聚合物杂质的含量。研究结果对其质量评价具有参考意义,为制定合理的杂质限度,更好地控制药品质量打下基础。
Objective: To establish a method to determination of the related substances and polymer impurities in cefminox sodium for injection. Method: Cefminox sodium was degraded in high temperature to prepare degradation solution. An RP-HPLC method for the related substances analysis was established with a Kromisil C18 column (250 mm×4.6 mm, 5 μm), using 10 mmol · L-1 phosphate buffer solution (pH 2.0)-acetonitrile (98∶2) (A)-acetonitrile (B) with gradient elution at a flow rate of 1.0 mL · min-1. The column temperature was maintained at 25 ℃, the detection wavelength was set at 254 nm, and the injection volume was 20 μL. The specificity of RP-HPLC method and identification of unknown impurities was researched by 2D HPLC-MS/MS. Results: 14 main impurities were characterized in the degradation solution, including 3 cefminox dimmers and isomers which were characterized firstly. The impurities were determined in 7 batches of samples by principal component self-control with correction factor, the contents of impurity 3 were 0.01%-0.13%, the contents of impurity 4 were 0.10%-0.16%, the contents of impurity 5 were 0.02%-0.07%, the contents of impurity 6 were 0.04%-0.07%, the contents of polymer impurities were 0.03%-0.06%, the maximum single impurity contents were 0.01%-0.03%, while the total impurity contents were 0.28%-0.63%. Conclusion: Cefminox degradation solution in high temperature can be used to identify related impurities and polymer peaks as the systematic suitability testing solution. The RP-HPLC method was suitable for related substances as well as polymer impurities in cefminox sodium for injection. This work provides useful information for the quality control of cefminox sodium, which can contribute to establishment of reasonable impurity limits.
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