两种测定盐酸伊立替康脂质体注射液中蔗糖八硫酸酯定量法的比较

Comparison of two methods for the determination of sucrose octasulfate concentration in irinotecan hydrochloride liposomes

采用高效液相色谱-示差折光检测器(HPLC-RID)和高压离子色谱-电导检测器(HPIC-CD)对盐酸伊立替康脂质体注射液中蔗糖八硫酸酯进行含量测定并比较,为脂质体制剂提供科学有效的分析方法。HPLC-RID法:采用Kromasil 100-5-NH2柱(250 mm×4.6 mm,5μm),以0.8 mol·L-1硫酸铵溶液(pH 3.5)-乙腈(83∶17)为流动相,柱温30℃,检测器温度30℃,流速1.0 mL·min-1。HPIC-CD法:采用Dionex InPacTMAS11-HC阴离子交换柱(250 mm×4 mm,9μm),流速1.5 mL·min-1,柱温30℃,检测器温度35℃,淋洗液30 mmol·L-1氢氧化钠溶液。结果表明HPLCRID法和HPIC-CD法的专属性、检测限、定量限、线性、精密度、准确度、稳定性以及耐用性验证均符合要求。两种方法均可准确测定盐酸伊立替康脂质体注射液中蔗糖八硫酸酯的含量,经过独立样本T-检验表明两种方法测得结果无显著性差异。与HPLC-RID法相比,HPIC-CD法具有专属性强、灵敏度高、分析速度快、操作简便、成本低、环保等优点。

HPLC-RID and HPIC-CD methods were established for the determination of sucrose octasulfate content in irinotecan hydrochloride liposomes for injection.HPLC-RID:This method was performed on a Kromasil100-5-NH2 column(250 mm×4.6 mm,5μm)with a mobile phase of 0.8 mol·L-1 ammonium sulfate buffer(pH 3.5)-acetonitrile(83∶17).The flow rate,column temperature and detector temperature were maintained at 1 mL·min-1,30℃and 30℃respectively.HPIC-CD:This method was performed on an anion exchange column Dionex InPacTMAS11-HC(250 mm×4 mm,9μm)with an eluent of 30 mmol·L-1 sodium hydroxide solution.The flow rate was 1.5 mL·min-1,the column temperature was 30℃and the detector temperature was 35℃.The HPLC-RID method and HPIC-CD method were validated with respects to specificity,limit of detection,limit of quantitation,linearity,precision,accuracy,stability and robustness and met the validation requirements.There were no significant differences between the HPIC-CD and HPLC-RID methods according to T-test analysis,both of which were applicable for the measurement of sucrose octasulfate concentration in irinotecan hydrochloride liposomes for injection.However,the HPLC-CD was better at the following aspects:higher detection sensitivity,simpler sample pretreatment,lower time and money spent,better environmental protection.