不同厂家左炔诺孕酮原料药及片剂中右旋体存在状况考察
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摘要
目的:考察不同厂家左炔诺孕酮原料药及片剂中是否存在无活性右旋体,并对高温、高湿、光照破坏的原料药进行考察,以了解贮存时的变化情况。方法:采用高效液相色谱法。色谱柱为Hypersil ODS,流动相为甲醇-1%γ-环糊精(50∶50),流速为1.2ml/min,检测波长为242nm,柱温为30℃。分析来源于2个厂家的11批次原料药、7个厂家的19批片剂(包括放置3年的1批样品)、1个厂家的2批肠溶片、原研片及经光、湿、热破坏的原料药中右旋体的存在情况。结果:在采用的色谱条件下,左炔诺孕酮与右旋体分离良好,右旋体检测限为1 ng;各检品中均未检出右旋体。结论:建立的方法专属性强、灵敏且环保;推导该药在原料合成时即可以控制左炔诺孕酮的光学纯度,制剂稳定性好,贮存期间不会因光、湿、热等因素产生右旋体。
OBJECTIVE:To investigate if any inactive dextroisomer is in levonorgestrel drug substance or Levonorgestrel tablets from different sources,and to investigate levonorgestrel drug substance treated with heat,moisture and light to study the change of storage. METHODS:HPLC method was adopted. The determination was performed on Hypersil ODS column with mobile phase consisted of methanol-1% γ-cyclodextrin(50 ∶ 50)at the flow rate of 1.2 ml/min. The detection wavelength was set at242 nm,and the column temperature was 30 ℃. The inactive dextroisomer were analyzed in 11 batches of drug substance from 2manufacturers,19 batches of tablet from 7 manufacturers(containing 1 batch of sample after kept for 3 years),2 batches of enteric-coated tablet from 1 manufacturer,original tablet and drug substance treated with heat,moisture and light. RESULTS:Dextroisomer was well separated from levonorgestrel under above chromatogram condition,and the limit of detection was 1 ng. No dextroisomer was found in samples. CONCLUSIONS:Established method is specific,sensitive and environmental. It can control the optical purity of levonorgestrel during synthesis process through the derivation. The preparation is stable,and no dextroisomer is produced due to light,moisture or heat during storage.
OBJECTIVE:To investigate if any inactive dextroisomer is in levonorgestrel drug substance or Levonorgestrel tablets from different sources,and to investigate levonorgestrel drug substance treated with heat,moisture and light to study the change of storage. METHODS:HPLC method was adopted. The determination was performed on Hypersil ODS column with mobile phase consisted of methanol-1% γ-cyclodextrin(50 ∶ 50)at the flow rate of 1.2 ml/min. The detection wavelength was set at242 nm,and the column temperature was 30 ℃. The inactive dextroisomer were analyzed in 11 batches of drug substance from 2manufacturers,19 batches of tablet from 7 manufacturers(containing 1 batch of sample after kept for 3 years),2 batches of enteric-coated tablet from 1 manufacturer,original tablet and drug substance treated with heat,moisture and light. RESULTS:Dextroisomer was well separated from levonorgestrel under above chromatogram condition,and the limit of detection was 1 ng. No dextroisomer was found in samples. CONCLUSIONS:Established method is specific,sensitive and environmental. It can control the optical purity of levonorgestrel during synthesis process through the derivation. The preparation is stable,and no dextroisomer is produced due to light,moisture or heat during storage.
引文
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[2]上海有机化学所一室.光学活性18-甲基炔诺酮鉴定会[J].有机化学,1981(3):177.
[3]国家药典委员会.中华人民共和国药典:二部[S].2010年版.北京:中国医药科技出版社,2010:104-105、附录194-195.
[4]美国药典委员会.USP36-NF31[S].Rockville:The United States Pharmacopeial Convention,2013:4 102.
[5]欧洲药典委员会.European Pharmacopoeia 7.0[S].Strasbourg:Council of Europe,2011:2 363.
[6]英国药典委员会.British Pharmacopoeia[S].London:The Stationery Office,2011:2 938.
[7]周燕.手性氨基醇类催化剂的设计合成及其在硼烷对前手性酮不对称还原反应中的应用研究[D].兰州:兰州大学,2008:67-72.
[8]钱慧芬(.1R,3S)-樟脑酸制备(1S,3R)-樟脑酸酐过程中构型翻转的研究[J].南京工业大学学报,2001,26(4):35.
[9]程民.色谱法拆分手性药物在我国的应用[J].中国药房,2011,22(13):1 220.