上海杂质检查发出稿课件.ppt

药品杂质检查研究要求探讨;一 前言;前言;凡例中关于杂质的叙述;中国药典指导性附录关于杂质的说明;中国药典指导性附录关于杂质的说明;二 杂质的类别;;杂质类别;;;中国药典指导性附录关于杂质分类叙述;中国药典指导性附录关于杂质分类叙述;各类杂质的定义;;;;;;;;;;;;;中国药典关于杂质名称的叙述;中国药典关于杂质名称的叙述;;;;;Impurity Table 1 ;USP Atorvastatin Related Compound A RS Desfluoro impurity, or (3R,5R)-7-[3-(phenylcarbamoyl)-2-isopropyl-4,5-diphenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid, calcium salt.????????C66H70CaN4O101119.38 USP Atorvastatin Related Compound B RS 3S,5R Isomer, or (3S,5R)-7-[3-(phenylcarbamoyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid, calcium salt.????????C66H68CaF2N4O101155.34 USP Atorvastatin Related Compound C RS Difluoro impurity, or (3R,5R)-7-[3-(phenylcarbamoyl)-4,5-bis(4-fluorophenyl)-2-isopropyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid, calcium salt.????????C66H66F4N4O101191.34 USP Atorvastatin Related Compound D RS Epoxide impurity, or 3-(4-fluorobenzoyl)-2-isobutyryl-3-phenyl-oxirane-2-carboxylic acid phenylamide.????????C26H22FNO4431.46 USP Atorvastatin Related Compound E RS 3S,5S Enantiomer, or (3S,5S)-7-[3-(phenylcarbamoyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid, calcium salt.????????C66H68CaF2N4O101155.34 ;对映异构体单列对映体纯度检查项;;;三 杂质研究;;;;;;;;;;;;;;;;;;;;;;;;四 中国药典杂质检查现况;Monograph revision of 2010 ChP;前列地尔及其制剂注射用前列地尔 2010版有关物质检查较2005年版有所提高，均用HPLC,ODS柱，流动相和检测波长改变（214nm,200nm),05版相对保留值定位，限度，总杂质:原料5.0%，制剂10.0% 2010版，用杂质对照品（前列腺素A1,B1）定位和计算，限度1.5%,0.5%,其他杂质最大不得过1.0%，总量2.0%, 制剂限度分别为：3.0,1.5,2.0和5.0% ;对映体杂质Resolution of enantiomer impurity;甲氨蝶呤 增订R-甲氨蝶呤，用牛血清白蛋白柱，RS,R 大于3.0, 限度3.0% Methotrexate Test for R-form is added to the 2010 monograph, using bovine albumin column,302nm detection, resolution not less than 3.0, limit:3.0%;盐酸帕罗西汀 本品为反式异构体，4R3S 检查3R4S异构体，用CHIRAL-AGP柱，对映体对照品作系统适用性试验，R4R3S/3R4S应大于2.2,限度0.1% Paroxetine hydrochloride ( 4R3S of trans form) 3R4S enantiomer of the transform is detected using AGP column, the enantiomer reference substnces are used for system su