【作者】 孙伟；

【导师】 杨祥良；

【作者基本信息】 华中科技大学 ， 生物化工， 2007， 硕士

【摘要】 羟乙基淀粉480/0.7乳酸盐注射液是高相对分子质量人工血浆代用品,用于救治因大量出血、烧伤或其它外伤引起的休克或出血症,是血浆代用品美国市场上的主打品种。本文主要是根据美国上市的羟乙基淀粉480/0.7乳酸盐注射液配方,对制剂中的各个组分的测定进行了方法学研究,主要内容有:(1)采用HPLC法,用十八烷基硅烷键合硅胶为填充剂,流动相:1 L水中含1 mL甲酸和1 mL二环己基胺。建立了羟乙基淀粉480/0.7注射液中乳酸钠含量测定方法。乳酸钠在0.1 mg/mL～1.2 mg/mL范围内有良好的线性关系,乳酸钠最小检出量为0.25μg。HES480制剂其他成分对主峰无干扰,方法的稳定性好、精密度高、平均回收率达到101%,RSD为1.04%。乳酸钠对光、热、酸、碱均稳定,主峰面积基本没有变化。(2)采用HPLC法,用氨基键合相为填充剂,甲醇:水=80:20为流动相,RID检测器,建立了羟乙基淀粉480/0.7注射液中葡萄糖含量测定方法。葡萄糖在0.04 mg/mL～0.4 mg/mL范围内线性关系良好,最小检出量为0.80μg。待测溶液稳定,精密度高,方法平均回收率为100.5%,RSD为1.4%。(3)采用旋光法,建立了羟乙基淀粉480/0.7乳酸钠注射液中羟乙基淀粉的测定方法。羟乙基淀粉在10 mg/mL～90 mg/mL范围内,线性关系良好,空白无干扰,方法平均回收率为99.8%,RSD为0.38%。(4)采用原子吸收分光光度法,建立了羟乙基淀粉480/0.7乳酸钠注射液中CaCl2、MgCl2含量测定的方法。钙和镁在1μg/mL～5μg/mL范围内,线性关系均良好,且重复性好,氯化钙平均回收率为101%,RSD为1.2%,氯化镁平均回收率为101.5%,RSD为0.9%。(5)参考药典方法,对制剂中的各个组分进行了鉴别,结果均符合要求。更多还原

【Abstract】 Hydroxyethyl starch 480/0.7（HES480/0.7） lactate injection, a kind of high molecular weight artificial plasma substitutes with long expansion effect, which can be used for treatment of hemorrhage or shock caused by massive bleeding, burn or other injury, is a widely used plasma substitute in the United States. Based on the injection formula of the product, this paper has focused on establishing the methodology of various components in the HES480/0.7 lactate injection. The mainly results are as follows:（1） HPLC method was used for the determination of sodium lactate in the HES480/0.7 lactate injection. HPLC separation was carried out on a C18 column （ODS HYPERSIL 200mm×4.6mm lichrospher） with the mobile phase consisting of 0.1% formic acid and 0.1% dicyclohexylamine in water. The results showed that the calibration curve was linear in the concentration range of 0.1 mg/mL to 1.2 mg/mL and the detection limit was 0.25μg. Other components in the HES480 preparation showed no interference. The average recovery was 101 % with RSD of 1.04 %. Light, heat, acid and alkali showed no impact to the main peak of lactate sodium.（2） HPLC method was established for the determination of glucose in the HES480/0.7 lactate injection. The analysis was conducted with a NH2 column （4.6mmID B115 Y525） and a RID detector, and the mobile phase was methanol-water （80:20）. The results indicated that the glucose was linear over the range of 0.04 mg/mL to 0.4 mg/mL and the detection limit was 0.80μg. The sample solution was stable and the mean recovery was 100.5 % with RSD of 1. 4 %.（3） Polarimetry analysis was used to determine the hydroxyethyl starch in HES480/0.7 lactate injection. The linear relationship of HES content was good over the range of 10 mg/mL to 90 mg/mL and the blank solution showed no interruption. The average recovery was 99.8 % with RSD of 0.38 %.（4） Atomic absorption spectrophotometry was carried out for determination of CaCl₂ and MgCl₂ in HES480/0.7 lactate injection. . The calibration curve was good linear in the range of 1μg/mL～5μg/mL for Ca²⁺ and Mg²⁺ . The average recovery of Ca²⁺ was 101% with RSD of 1.2%, and 101.5% of Mg²⁺ with RSD of 0.9 %. （5） All of the components in HES480/0.7 lactate injection were identified according to the Pharmacopoeia, and the results are in line with the requirements.更多还原