硫酸吗啡原料药中有关物质检查方法研究

目的 通过对硫酸吗啡原料药的有关物质进行分析,考察现行标准的完善性,探讨存在的问题,为提高产品质量标准提供参考。方法 采用HPLC,选用Symmetry C₁₈(4.6 mm×150 mm,5 μm)色谱柱,以1.01 g·L^-1庚烷磺酸钠溶液(用50%磷酸调节pH值至2.6)和甲醇为流动相进行梯度洗脱;检测波长为230 nm,流速为1.5 mL·min^-1,柱温35 ℃。结果 国内硫酸吗啡原料药中检出的主要杂质有可待因(杂质A)、伪吗啡(杂质B)、10-羟基吗啡(杂质D)、吗啡酮(杂质E)和吗啡氮氧化物(杂质F),溶液稳定性显示其中伪吗啡含量增加明显,表明样品需临用新配。结论 建立方法的专属性、线性等均良好,能用于硫酸吗啡原料药中有关物质的检测。现行标准中缺少有关物质检查项,建议增加。

Detection Method of Related Substances in Morphine Sulfate

OBJECTIVE To analyze the impurities in morphine sulfate, investigate and discuss the completeness of the current statutory standard and the existing problems, thus to provide reference for improvement of the quality standard and product quality. METHODS HPLC was performed on a Symmetry C₁₈column(4.6 mm×150 mm, 5 μm) with a gradient elution system of 1.01 g·L^-1 sodium heptanesulfonate(pH was adjusted to 2.6 with 50% phosphoric acid)-methanol at a flow rate of 1.5 ml/min, while the column temperature was maintained at 35 ℃, the detection wavelength was set at 230 nm. RESULTS The main impurities inmorphine sulfate were impurity A(codeine), impurity B(2, 2'-bimorphine), impurity D(10S-hydroxymorphine), impurity E(morphinone) and impurity F(morphine N-oxide). The stability test of the solution showed that the content of 2, 2'-bimorphine increased obviously, which indicated that the solution sample should be prepared just before the test. CONCLUSION The HPLC method has good specificity and linearity,which is suitable for the determination of related substances in morphine sulfate. There is a lack of detection of related substances in the current statutory standard, which is suggested to be added.