CN115166104A - 将匹伐他汀钙起始物料和其杂质进行分离的方法和应用 - Google Patents
将匹伐他汀钙起始物料和其杂质进行分离的方法和应用 Download PDFInfo
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- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1790012A (zh) * | 2005-12-12 | 2006-06-21 | 重庆医药工业研究院有限责任公司 | 一种用液相色谱法分离测定匹伐他汀及其光学异构体的方法 |
CN102279241A (zh) * | 2011-07-14 | 2011-12-14 | 北京汉典中西药研究开发中心 | 阿托伐他汀钙胶囊有关物质的检测方法 |
CN106706789A (zh) * | 2016-12-26 | 2017-05-24 | 江苏联环药业股份有限公司 | 用高效液相色谱法测定盐酸屈他维林注射液中有关物质的方法 |
CN111505150A (zh) * | 2020-04-30 | 2020-08-07 | 山东齐都药业有限公司 | 匹伐他汀钙片中潜在致突变杂质的检测方法 |
CN113092597A (zh) * | 2019-12-23 | 2021-07-09 | 徐州万邦金桥制药有限公司 | 一种匹伐他汀钙中间体有关物质的分析方法 |
CN114076802A (zh) * | 2020-08-21 | 2022-02-22 | 徐州万邦金桥制药有限公司 | 一种定量检测匹伐他汀钙中氮氧杂质的分析方法 |
CN114280181A (zh) * | 2021-12-23 | 2022-04-05 | 浙江海翔川南药业有限公司 | 一种瑞舒伐他汀中间体及其有关物质的检测方法 |
CN114295748A (zh) * | 2021-12-30 | 2022-04-08 | 苏州正济药业有限公司 | 一种匹伐他汀钙中间体及杂质的检测方法 |
CN114384178A (zh) * | 2021-12-30 | 2022-04-22 | 苏州正济医药研究有限公司 | 一种匹伐他汀钙中间体及杂质的检测方法 |
-
2022
- 2022-09-08 CN CN202211092987.5A patent/CN115166104B/zh active Active
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1790012A (zh) * | 2005-12-12 | 2006-06-21 | 重庆医药工业研究院有限责任公司 | 一种用液相色谱法分离测定匹伐他汀及其光学异构体的方法 |
CN102279241A (zh) * | 2011-07-14 | 2011-12-14 | 北京汉典中西药研究开发中心 | 阿托伐他汀钙胶囊有关物质的检测方法 |
CN106706789A (zh) * | 2016-12-26 | 2017-05-24 | 江苏联环药业股份有限公司 | 用高效液相色谱法测定盐酸屈他维林注射液中有关物质的方法 |
CN113092597A (zh) * | 2019-12-23 | 2021-07-09 | 徐州万邦金桥制药有限公司 | 一种匹伐他汀钙中间体有关物质的分析方法 |
CN111505150A (zh) * | 2020-04-30 | 2020-08-07 | 山东齐都药业有限公司 | 匹伐他汀钙片中潜在致突变杂质的检测方法 |
WO2021217887A1 (zh) * | 2020-04-30 | 2021-11-04 | 山东齐都药业有限公司 | 匹伐他汀钙片中潜在致突变杂质的检测方法 |
CN114076802A (zh) * | 2020-08-21 | 2022-02-22 | 徐州万邦金桥制药有限公司 | 一种定量检测匹伐他汀钙中氮氧杂质的分析方法 |
CN114280181A (zh) * | 2021-12-23 | 2022-04-05 | 浙江海翔川南药业有限公司 | 一种瑞舒伐他汀中间体及其有关物质的检测方法 |
CN114295748A (zh) * | 2021-12-30 | 2022-04-08 | 苏州正济药业有限公司 | 一种匹伐他汀钙中间体及杂质的检测方法 |
CN114384178A (zh) * | 2021-12-30 | 2022-04-22 | 苏州正济医药研究有限公司 | 一种匹伐他汀钙中间体及杂质的检测方法 |
Non-Patent Citations (8)
Title |
---|
刘静等: "RP-HPLC法测定阿托伐他汀钙原料药", 《现代药物与临床》 * |
唐开勇等: "匹伐他汀钙有关物质的HPLC法测定", 《中国医药工业杂志》 * |
张亚平等: "HPLC法检测阿托伐他汀钙有关物质的含量及光学纯度", 《药物分析杂志》 * |
曹建军等: "高效液相色谱法分离和测定匹伐他汀钙对映体及其含量", 《药物分析杂志》 * |
梁敏等: "HPLC法测定匹伐他汀钙中6种有关物质", 《中国药事》 * |
程晓昆等: "毛细管区带电泳法拆分匹伐他汀钙对映体", 《色谱》 * |
童成亮等: "高效毛细管电泳法测定匹伐他汀钙对映体异构体含量", 《药物分析杂志》 * |
郭晓静等: "RP-HPLC法测定匹伐他汀钙的含量", 《药物分析杂志》 * |
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Effective date of registration: 20240419 Address after: 301606 Tai'an Road, Jinghai Economic Development Zone, Binhai New Area, Tianjin Patentee after: TIANJIN MINXIANG PHARMACEUTICAL Co.,Ltd. Country or region after: China Address before: Room 602, Building 1, TEDA Small and Medium Enterprise Park, No. 276 Huanghai Road, Economic and Technological Development Zone, Binhai New Area, Tianjin 300457 Patentee before: Kangruixin (Tianjin) Pharmaceutical Research Institute Co.,Ltd. Country or region before: China |