硝酸咪康唑原料及其制剂有关物质测定方法的建立

目的: 建立硝酸咪康唑原料及制剂中4个已知杂质及其他未知杂质检测方法。 方法: 采用Kromasil C₁₈色谱柱(150 mm× 4.6 mm,5 μm),柱温:45℃,流动相:以0.5%醋酸铵溶液(pH 4.4)-甲醇不同比例线性梯度洗脱,流速:2 mL·min^-1,检测波长:235 nm。 结果: 4个已知杂质分别在0.04~1.2 μg范围内线性关系良好,相关系数(n=6)分别为0.9983,0.9999,0.9995,0.9992;最低检出限量分别为43.84 ng、83.20 ng、20.88 ng及20.92 ng;原料、乳膏及栓剂中4个已知杂质的平均回收率分别为100.3%,84.3%,90.7%,84.7%;95.5%;85.3%,90.9%,85.8%和92.4%,85.9%,89.9%,83.3%。 结论: 该方法简便,定量准确,可有效控制硝酸咪康唑原料及制剂中杂质含量。

Objective: To establish a method to detect four kinds of known impurities and others unknown impurities in miconazole nitrate crude drug and preparation. Methods: The HPLC analysis was performed on a Kromasil C₁₈(150 mm×4.6 mm,5 μm)column;the column temperature was 45℃;the mobile phase consisted of methanol and 0.5% ammonium acetate with a gradient elution at the flow rate of 2.0 mL·min^-1;the detection wavelength was 235 nm. Results: Four kinds of impurities were completely separated in 25 minutes,and good linear relationships were obtained in the range of 0.04-1.2 μg.The correlation coefficient were respectively 0.9983(n=6),0.9999(n=6),0.9995(n=6)and 0.9992(n=6);the limit of detection of were respectively 43.84 ng,83.20 ng,20.88 ng and 20.92 ng;the average recoveries were respectively 100.3%,84.3%,90.7% and 84.7%. Conclusion: The method is simple,accurate for quantitation and can be used for the quality control of the crude drug and preparation of miconazole nitrate efficiently.

1 LIU Hai-ling(刘海玲),WU Yan(吴燕),CAO Xiao-yun(曹晓云).Assay of two impuritie s in miconazole nitrate suppository by high performance liquid chromatography(高效液相色谱法测定硝酸咪康唑栓中两种杂质的含量).Tianjin Pharm(天津药学),2002,14(1):65
2 ZHUANG Jiang-xing(庄江兴),CHEN Yu-lin(陈育琳),LIN Tian-cong(林恬聪).Assay of miconazole nitrate in compound miconazole nitrate ointment by high performance liquid chromatography(HPLC法测定复方硝酸咪康唑软膏中硝酸咪康唑的含量).J Strait Pharm(海峡药学),2004,16(5):80
3 ZHOU Feng-ying(周凤英),LI Hui-min(李慧敏).Improvement of assay for miconazole nitrate ointment by high performance liquid chromatography(HPLC法测定硝酸咪康唑乳膏含量方法的改进).J Chin Pharm(中国药事),2009,23(11):1117
4 CHEN Shu-xin(陈树新),CAI Xian-dong(蔡先东),LU Ying(陆颖).Assay of miconazole nitrate in solution by the two-phase titration(双相滴定法测定硝酸咪康唑溶液的含量).Chin J Ethnomed Ethnopharm(中国民族民间医药),2009,18(10):12
5 XIE Zi-li(谢子立),WU Gu(武谷).Assay of miconazole nitrate and propionate Clobetasol in compound miconazole ointment(HPLC法测定复方咪康唑软膏中硝酸咪康唑和丙酸氯倍他索的含量).Anhui Med Pharm J(安徽医药),2001,5(1):69
6 ChP(中国药典).2010.VolⅡ(二部):952
7 LIU Jian-hua(刘建华),YIN Ji-ye(尹继业),YANG De-zhu(杨得柱).Establishment of related substance examination in miconazole nitrate ointment(硝酸咪康唑软膏有关物质检查方法的建立).Her Med(医药导报),2007,26(9):1081
8 PAN Fu-you(潘富友),LIANG Hua-ding(梁华定),HU Mei-lian(胡美莲),et al.Assay of miconazole nitrate and its related substance by reversed phase high performance liquid chromatography (反相高效液相色谱法测定硝酸咪康唑及其相关物质的含量).J Anal Sci(分析科学学报),2004,20(6):667
9 LIN Yin-feng(林银凤).Assay of miconazole nitrate and propanoic acid clobetasol in moss ointment by reversed phase high performance liquid chromatography(反相高效液相色谱法测定藓药膏中硝酸咪康唑和丙酸氯倍他索的含量).J Strait Pharm(海峡药学),2012,24(2):66
10 EP5.0.2043
11 FU Qiang(傅强).Experiment Methodology for Pharmaceutical Analysis(药物分析实验方法学).Beijing(北京):People’s Health Publishing House(人民卫生出版社),2008.54
12 Chinese Pharmacopoeia Commission(国家药典委员会).Guide Clinical Treatment(临床用药须知).Beijing(北京):People’s Health Publishing House(人民卫生出版社),2005.953