HPLC法检测硫酸吗啡片的有关物质  

Detection of related substances in morphine sulfate tablets by HPLC

作　　者：王雯慧 张敏娟 陈学艳 魏文芝 WANG Wen-hui;ZHANG Ming-juan;CHEN Xue-yan;WEI Wen-zhi(Qinghai Univeisity,Xining 810003,China;Qinghai Provincial Drug Inspection and Testing Institute,Xining 810003,China;Qinghai Key Lab of Chinese and Tibetan Medicine Modernization Study,Xining 810003,China)

机构地区：[1]青海大学,西宁810003 [2]青海省药品检验检测院,西宁810003 [3]青海省中藏药现代化研究重点实验室,西宁810003

出　　处：《药物分析杂志》2022年第4期660-667,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：青海省科技计划项目-药品检验检测平台项目(No.2017-ZJ-Y40)。

摘　　要：目的:建立硫酸吗啡片中有关物质的HPLC检测方法。方法:采用Symmetry C_(18)色谱柱(150 mm×4.6 mm,5μm),以庚烷磺酸钠溶液(取庚烷磺酸钠1.01g,加水1000 mL溶解,用磷酸调节pH至2.6)为流动相A,甲醇为流动相B,梯度洗脱,流速1.5 mL·min^(-1),柱温35℃,检测波长230 nm,进样量20μL。结果:硫酸吗啡与各杂质以及各杂质间均能达到很好分离。硫酸吗啡质量浓度在2.026~2532μg·mL^(-1);范围内线性关系良好(r=0.9999);杂质A、B、C、D、E、F质量浓度分别在0.195~5.847、0.305~17.080、0.154~6.172、0.198~5.929、0.473~6.626、0.420~6.294μg·mL^(-1);范围内线性关系良好,相关系数分别为0.9998、0.9999、0.9998、0.9998、0.9998、0.9999。硫酸吗啡检测限为0.068μg·mL^(-1),杂质A、B、C、D、E、F检测限分别为0.059、0.092、0.047、0.060、0.143、0.127μg·mL^(-1);硫酸吗啡定量限为0.224μg·mL^(-1),杂质A、B、C、D、E、F定量限分别为0.195、0.305、0.154、0.198、0.473、0.420μg·mL^(-1)。3批样品共检出6个主要杂质,其中包括杂质A、B、D、E、F和1个未知杂质,均未检出杂质C,其他杂质均符合相应限度规定。结论:本法可准确检测硫酸吗啡片中杂质A、B、C、D、E、F。Objective:To establish an HPLC method for the detection of related substances in morphine sulfate tablets.Methods:Symmetry C_(18)(150 mm×4.6 mm,5μm)chromatographic column was adopted.Sodium heptane sulfonate solution(1.01 g of sodium heptane sulfonate was dissolved in 1000 mL of water,and the pH was adjusted to 2.6 with phosphoric acid.)was used as mobile phase A,and methanol was used as mobile phase B.Using gradient elution,the flow rate was 1.5 mL·min^(-1),the column temperature was 35℃,the detection wavelength was 230 nm,and injection volume was 20μL.Results:Morphine sulfate could be well separated from the impurities,and the impurities could also be separated well.Morphine sulfate had a good linear relationship in the range of 2.026-2532μg·mL^(-1);(r=0.9999).The mass concentrations of impurities A,B,C,D,E,andF were within the range of 0.195-5.847,0.305-17.080,0.154-6.172,0.198-5.929,0.473-6.626,and 0.420-6.294μg·mL^(-1);,respectively.The linear relationship was good,and the correlation coefficients were 0.9998,0.9999,0.9998,0.9998,0.9998,0.9999,respectively.The detection limit of morphine sulfate was 0.068μg·mL^(-1);,and the detection limits of impurities A,B,C,D,E,and F were 0.059,0.092,0.047,0.060,0.143,0.127μg·mL^(-1);.Morphine sulfate quantification limit was 0.224μg·mL^(-1);,and the detection limits of impurities A,B,C,D,E,F were 0.195,0.305,0.154,0.198,0.473,0.420μg·mL^(-1);,respectively.Six major impurities were detected in the three batches of samples,including impurities A,B,D,E,F and an unknown impurity,but no impurity C was detected.Other impurities were conformed to the corresponding limits.Conclusion:This method can determine impurities A,B,C,D,E,F in morphine sulfate tablets.

关 键 词：高效液相色谱法 梯度洗脱 硫酸吗啡片 麻醉药品 受体激动剂 有关物质 

分 类 号：R917[医药卫生—药物分析学]