盐酸罂粟碱注射液含量测定及有关物质研究

Study on determination of papaverine hydrochloride injection and its related substances

目的:针对盐酸罂粟碱注射液现行标准中采用非水滴定进行含量测定且未对注射液中有关物质进行控制,建立了一种同时测定含量和有关物质的HPLC方法,并对注射液中存在的杂质用HPLC-MS联用技术进行结构推断。方法:采用C18色谱柱(SepaxGP,250 mm×4.6 mm,5μm),以0.005 mol.L-1庚烷磺酸钠的0.01 mol.L-1磷酸二氢钾溶液(以磷酸调pH至3.0)-甲醇(50∶50)为流动相,流速1.0 mL.min-1,检测波长254 nm。结果:在本文色谱条件下,主峰和杂质峰能得到良好的分离;盐酸罂粟碱浓度在0.5～150μg.mL-1范围内与峰面积呈良好线性关系,r=0.9997;平均回收率(n=9)为101.7%。用HPLC-MS对注射液中杂质分析的结果表明:注射液的杂质为光氧化产物,它可能是注射液颜色变深的原因之一。结论:该法专属性强,灵敏、准确,耐用性好,可作为盐酸罂粟碱注射液的质量控制方法。

Objective：To establish an HPLC method for the determination of papaverine hydrochloride injection and its related substances.Methods：The separation was performed on a C18 column（250 mm×4.6 mm,5 μm） with a mixture of 0.005 mol·L-1 heptane sulfonate sodium in 0.01 mol·L-1 potassium dihydrogen phosphate solution（adjusted to pH 3.0 with phosphoric acid）-methanol（50∶50） as the mobile phase;The flow rate was 1.0 mL·min-1,and the UV detection wavelength was 254 nm.Liquid chromatographic method coupled with electrospray ionization-mass spectrometry（LC-MS） was also used to identify the related substances.Results：The new method showed good resolution and a linearity between peak area and papaverine hydrochloride concentration was achieved in the range of 0.5-150 μg·mL-1 with r=0.9997;The average recoveries（n=9） was 101.7%.The impurity in injection may be from photooxidation products according to LC-MS.Conclusion：The method is proved to be specific,sensitive and accurate,and can be used to control the quality of papaverine hydrochloride injection.