摘要
目的:针对硫酸吗啡栓含量测定方法中萃取溶剂毒性较高以及色谱条件专属性、通用性欠佳的问题进行优化。方法:供试品溶液制备方法的优化是采用冰浴冷冻法和正庚烷萃取法制备供试品溶液,并与美国药典方法(三氯甲烷萃取)制备的供试品溶液进行含量测定结果的比较。含量测定色谱条件的优化是在综合比较美国药典、英国药典以及YBH标准的基础上,最终采用Symmetry C18色谱柱(150 mm×4.6 mm, 5μm),以含0.202%庚烷磺酸钠的0.01 mol·L^(-1)磷酸二氢钾溶液(含0.1%三乙胺,用磷酸调节pH至2.5)-甲醇(70∶30)为流动相,流速为1.0 mL·min^(-1),柱温为30℃,检测波长为284 nm,进样体积为20μL。结果:采用冰浴冷冻法测得的含量偏低,而正庚烷萃取与三氯甲烷萃取的含量测定结果基本一致,说明可采用正庚烷替代卤代烷烃作为萃取溶剂。采用新建色谱方法,硫酸吗啡的线性范围为2.12~105.94μg·mL^(-1)(r=0.999 9),定量限为10.60 ng;系统精密度、重复性、中间精密度、稳定性的RSD均小于2%;平均回收率为98.6%~99.6%,RSD为0.21%~0.66%;供试品溶液经强制降解后主峰与各降解杂质均能够实现良好的分离,专属性良好;通过改变流速、柱温、pH、流动相比例以及色谱柱品牌,均能够实现主峰与各杂质峰的良好分离,耐用性良好。结论:本研究优化了硫酸吗啡栓的含量测定方法,供试品溶液的制备采用正庚烷代替了高毒性的卤代烷烃,同时改善了色谱条件,提高了方法的环保性、专属性和适用性,可用于硫酸吗啡栓含量的测定。
Objective:To optimize the content determination method of morphine sulfate suppositories,which had high toxicity of extraction solvent and poor specificity and generality of chromatographic conditions.Methods:The optimization of the preparation method for the test solution was to prepare the test solution by ice bath freezing and n-heptane extraction,and to compare the content determination results of the test solution prepared by the United States Pharmacopeia method(extracted with trichloromethane).The optimization of chromatographic conditions for content determination was based on the comprehensive comparison of United States Pharmacopeia,British Pharmacopeia and YBH specification.Symmetry C18 column(150 mm×4.6 mm,5μm)was finally used.The mobile phase was 0.01 mol·L^(-1) potassium dihydrogen phosphate solution containing 0.202%sodium heptane sulfonate(containing 0.1%triethylamine,adjusted to pH 2.5 with phosphoric acid)-methanol(70∶30).The flow rate was 1.0 mL·min^(-1).The column temperature was 30℃.The detection wavelength was 284 nm.The injection volume was 20μL.Results:The content measured by ice bath freezing method was relatively low,while the content measured by n-heptane extraction and trichloromethane extraction was basically consistent,indicating that n-heptane could be used as extraction solvent instead of halogenated alkane.The linear range of morphine sulfate was 2.12-105.94μg·mL^(-1)(r=0.9999),and the LOQ was 10.60 ng.The RSD values of system precision,repeatability,intermediate precision and stability were all less than 2%.The average recoveries were 98.6%-99.6%and RSD was 0.21%-0.66%.After forced degradation,the main peak of the tested solution could be separated from the degraded impurities,with good specificity.By changing the flow rate,column temperature,pH value,mobile phase ratio and column brand,the main peak could be well separated from each impurity peak,with good robustness.Conclusions:This study optimized the determination method for morphine sulfate suppositories.The preparation of the test solution used n-heptane instead of the highly toxic haloalkane,and meanwhile improved the chromatographic conditions,enhanced the environmental protection,specificity and applicability of the method.It can be used for the content determination of morphine sulfate suppositories.
作者
吕蓓蓓
张敏娟
魏文芝
陈学艳
LÜ Bei-bei;ZHANG Min-juan;WEI Wen-zhi;CHEN Xue-yan(Qinghai Provincial Drug Inspection and Testing Institute,Xining 810016,China;NMPA Key Laboratory for Quality Control of Traditional Chinese Medicine,Tibetan Medicine,Xining 810016,China;Qinghai Provincial Key Laboratory of Modernization of Traditional Chinese and Tibetan Medicine,Xining 810016,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2024年第6期1097-1104,共8页
Chinese Journal of Pharmaceutical Analysis
基金
青海省2022年第3批新开科技计划项目(No.青科发规[2022]84号)。
关键词
硫酸吗啡栓
冰浴
萃取
三氯甲烷
正庚烷
优化
含量测定
高效液相色谱
morphine sulfate suppositories
ice bath
extraction
trichloromethane
n-heptane
optimization
content determination
high performance liquid chromatography(HPLC)
