Desacetylcinobufagin_4026-95-3_DataSheet_MedChemExpress

双醋瑞因杂质湖北扬信医药科技有限公司序号货号中文名称名称CAS 品牌结构式
1234D 双醋瑞因Diacerein 13739-02-1STD
22341D 双醋瑞因Diacerein Impurity 1(Diacerein EP Impurity E)875535-36-7STD
32342D 双醋瑞因Diacerein Impurity 2(Diacerein EP Impurity D)875535-35-6STD
42343D 双醋瑞因Diacerein Impurity 3(Diacerein EP Impurity B)481-72-1STD
扬信医药代理各品种杂质对照品:阿比特龙、艾地苯醌、艾拉莫德、色氨酸、沙丁胺醇、沙库巴曲、双醋瑞因、苏沃雷生、西地那非、缬沙坦等杂质；并提供COA 、NMR 、HPLC 、MS 等结构确认图谱。

专业<杂质对照品>解决方案，代理中检所/EP/BP/USP/LGC/TRC/DR/TLC/MC/SIGMA/BACGEM/STD 等品牌。

52344D 双醋瑞因Diacerein Impurity 4(Diacerein EP Impurity C)478-43-3STD
62346D 双醋瑞因Diacerein Impurity 6(Diacerein EP Impurity G)64951-96-8STD
72347D 双醋瑞因Diacerein Impurity 7(Diacerein EP Impurity H)25395-11-3STD
等各种双醋瑞因杂质。

Ac Acetyl 乙酰基DMAP 4-dimethylaminopyridine 4-二甲氨基吡啶acac Acetylacetonate 乙酰丙酮基DME dimethoxyethane 二甲醚AIBN Azo-bis-isobutryonitrile 2,2'-二偶氮异丁腈DMF N,N'-dimethylformamide 二甲基甲酰胺aq. Aqueous 水溶液dppf bis (diphenylphosphino)ferrocene 双(二苯基膦基)二茂铁9-BBN 9-borabicyclo[3.3.1]nonane 9-硼二环[3.3.1]壬烷dppp 1,3-bis (diphenylphosphino)propane 1,3-双(二苯基膦基)丙烷BINAP (2R,3S)-2,2’-bis (diphenylphosphino)-1,1’-binaphthyl（2R,3S)-2.2'-二苯膦－1.1'-联萘亦简称为联二萘磷BINAP是日本名古屋大学的Noyori（2001年诺贝尔奖）发展的一类不对称合成催化剂dvb Divinylbenzene 二乙烯苯Bn Benzyl 苄基e- Electrolysis 电解BOC t-butoxycarbonyl 叔丁氧羰基（常用于氨基酸氨基的保护）%ee % enantiomeric excess 对映体过量百分比（不对称合成术语）%de % diasteromeric excess 非对映体过量百分比（不对称合成术语）Bpy (Bipy) 2,2’-bipyridyl 2,2'-联吡啶EDA (en) ethylenediamine 乙二胺Bu n-butyl 正丁基EDTA Ethylenediaminetetraacetic acid 乙二胺四乙酸二钠Bz Benzoyl 苯甲酰基EE 1-ethoxyethyl 乙氧基乙基c- Cyclo 环－Et Ethyl 乙基FMN Flavin mononucleotide 黄素单核苷酸CAN Ceric ammonium nitrate 硝酸铈铵Cat. Catalytic 催化Fp flash point 闪点CBz Carbobenzyloxy 苄氧羰基FVP Flash vacuum pyrolysis 闪式真实热解法h hours 小时Min Minute 分钟hv Irradiation with light 光照COT 1,3,5-cyclooctatrienyl 1,3,5-环辛四烯1,5-HD 1,5-hexadienyl 1，5－己二烯Cp Cyclopentadienyl 环戊二烯基HMPA Hexamethylphosphoramide 六甲基磷酸三胺CSA 10-camphorsulfonic acid 樟脑磺酸HMPT Hexamethylphosphorus triamide 六甲基磷酰胺CTAB Cetyltrimethylammonium bromide 十六烷基三甲基溴化铵（相转移催化剂）iPr isopropyl 异丙基Cy Cyclohexyl 环己基LAH Lithium aluminum hydride 氢化铝锂（LiAlH4）LDA Lithium diisopropylamide 二异丙基氨基锂（有机中最重要一种大体积强碱）2 有机化学合成常见缩写dba Dibenzylidene acetone 苄叉丙酮LHMDS Lithium hexamethyldisilazideDBE 1,2-dibromoethane 1,2- 二溴乙烷LTBA Lithium tri-tert-butoxyaluminum hydrideDBN 1,8-diazabicyclo[5.4.0]undec-7-ene 二环[5.4.0]-1,8-二氮-7-壬烯mCPBA meta-cholorperoxybenzoic acid 间氯过苯酸DBU 1,5-diazabicyclo[4.3.0]non-5-ene 二环[4.3.0]-1,5-二氮-5-十一烯Me Methyl 甲基DCC 1,3-dicyclohexylcarbodiimide 1，3－二环己基碳化二亚胺MEM b-methoxyethoxymethyl 甲氧基乙氧基甲基－DCE 1,2-dichloroethane 1,2-二氯乙烷Mes Mesityl 均三甲苯基（也就是1，3，5-三甲基苯基）不知对不对?DDQ 2,3-dichloro-5,6-dicyano-1,4-benzoquinone 2,3-二氯-5，6-二氰-1，4-苯醌MOM methoxymethyl 甲氧甲基DEA Diethylamine 二乙胺Ms Methanesulfonyl 甲基磺酰基（保护羟基用）TBDMS, TBS t-butyldimethylsilyl 叔丁基二甲基硅烷基（羟基保护基）DEAD Diethyl azodicarboxylate 偶氮二甲酸二乙酯MS Molecular sieves (3 or 4 ）分子筛Dibal-H Diisobutylaluminum hydride 二异丁基氢化铝MTM Methylthiomethyl 二甲硫醚diphos (dppe) 1,2-bis (diphenylphosphino)ethane 1,2-双(二苯基膦)乙烷Naphth Naphthyl 萘基diphos-4 (dppb) 1,4-bis (diphenylphosphino)butane 1,2-双(二苯基膦)丁烷NBD Norbornadiene 二环庚二烯（别名：降冰片二烯）NBS N-Bromosuccinimide N-溴代丁二酰亚胺别名：N-溴代琥珀酰亚胺NCS N-chlorosuccinimide N-氯代丁二酰亚胺. 别名：N-氯代琥珀酰亚胺TBAF Tetrabutylammonium fluoride 氟化四丁基铵TASF Tris(diethylamino)sulfonium difluorotrimethyl silicateNi(R) Raney Nickel 雷尼镍（氢活性催化还原剂）NMO N-methyl morpholine-n-oxide N-甲基氧化吗啉TBHP t-butylhydroperoxide 过氧叔丁醇PCC Pyridinium chlorochromate 吡啶氯铬酸盐PDC Pyridinium dichromate 是什么东西？t-Bu Tert-butyl 叔丁基TEBA Triethylbenzylammonium 三乙基苄基胺PEG Polyethylene glycol 聚乙二醇TEMPO Tetramethylpiperdinyloxy free radicalPh Phenyl 苯基PhH Benzene 苯TFA Trifluoroacetic acid 三氟乙酸TFAA Trifluoroacetic anhydride 三氟乙酸酐PhMe Toluene 甲苯（亦称toluol;methylbenzene）Tol Tolyl 甲苯基Tf or OTf TriflatePhth Phthaloyl 邻苯二甲酰3楼THF Tetrahydrofuran 四氢呋喃Pip Piperidyl 哌啶基THP Tetrahydropyranyl 四氢吡喃基TMEDA Tetramethylethylenediamine 四甲基乙二胺Py Pyridine 吡啶TMP 2,2,6,6-tetramethylpiperidine 2,2,6,6-四甲基哌啶quant. quantitative yield 定量产率(对否？）TMS Trimethylsilyl 三甲基硅烷基Red-Al [(MeOCH2CH2O)AlH2]Na 直接看分子式就是了sBu sec-butyl 仲丁基Tr Trityl 三苯基sBuLi sec-butyllithium 仲丁基锂TRIS TriisopropylphenylsulfonylSiamyl DiisoamylTs (Tos) Tosyl (p-toluenesulfonyl) 对甲苯磺酰基谢谢观星人，我们合贴吧……（所有的都翻译了）%%de 非对映体过量百分比（不对称合成术语）%ee 对映体过量百分比（不对称合成术语）AA/MMA 丙烯腈/甲基丙烯酸甲酯共聚物AA 丙烯酸AAS 丙烯酸酯-丙烯酸酯-苯乙烯共聚物ABFN 偶氮（二）甲酰胺ABN 偶氮（二）异丁腈ABPS 壬基苯氧基丙烷磺酸钠Ac 乙酰基acac 乙酰丙酮基AIBN 2,2'-二偶氮异丁腈aq. 水溶液BBAA 正丁醛苯胺缩合物BAC 碱式氯化铝BACN 新型阻燃剂BAD 双水杨酸双酚A酯BAL 2，3-巯（基）丙醇9-BBN 9-硼二环[3.3.1]壬烷BBP 邻苯二甲酸丁苄酯BBS N-叔丁基-乙-苯并噻唑次磺酰胺BC 叶酸BCD β－环糊精BCG 苯顺二醇BCNU 氯化亚硝脲BD 丁二烯BE 丙烯酸乳胶外墙涂料BEE 苯偶姻乙醚BFRM 硼纤维增强塑料BG 丁二醇BGE 反应性稀释剂BHA 特丁基-4羟基茴香醚BHT 二丁基羟基甲苯BINAP （2R,3S）-2.2'-二苯膦－1.1'-联萘，亦简称为联二萘磷，BINAP是日本名古屋大学的Noyori（2 001年诺贝尔奖）发展的一类不对称合成催化剂BL 丁内酯BLE 丙酮-二苯胺高温缩合物BLP 粉末涂料流平剂BMA 甲基丙烯酸丁酯BMC 团状模塑料BMU 氨基树脂皮革鞣剂BN 氮化硼Bn 苄基BNE 新型环氧树脂BNS β－萘磺酸甲醛低缩合物BOA 己二酸辛苄酯BOC 叔丁氧羰基（常用于氨基酸氨基的保护）BOP 邻苯二甲酰丁辛酯BOPP 双轴向聚丙烯BP 苯甲醇BPA 双酚ABPBG 邻苯二甲酸丁（乙醇酸乙酯）酯BPF 双酚FBPMC 2-仲丁基苯基-N-甲基氨基酸酯BPO 过氧化苯甲酰BPP 过氧化特戊酸特丁酯BPPD 过氧化二碳酸二苯氧化酯BPS 4，4’-硫代双（6-特丁基-3-甲基苯酚）BPTP 聚对苯二甲酸丁二醇酯Bpy 2,2'-联吡啶BR 丁二烯橡胶BRN 青红光硫化黑BROC 二溴（代）甲酚环氧丙基醚BS 丁二烯-苯乙烯共聚物BS-1S 新型密封胶BSH 苯磺酰肼BSU N，N’-双（三甲基硅烷）脲BT 聚丁烯-1热塑性塑料BTA 苯并三唑BTX 苯-甲苯-二甲苯混合物Bu 正丁基BX 渗透剂BXA 己二酸二丁基二甘酯BZ 二正丁基二硫代氨基甲酸锌Bz 苯甲酰基Cc- 环－CA 醋酸纤维素CAB 醋酸-丁酸纤维素CAM 甲基碳酰胺CAN 硝酸铈铵CAN 醋酸-硝酸纤维素CAP 醋酸-丙酸纤维素Cat. 催化CBA 化学发泡剂CBz 苄氧羰基CDP 磷酸甲酚二苯酯CF 甲醛-甲酚树脂,碳纤维CFE 氯氟乙烯CFM 碳纤维密封填料CFRP 碳纤维增强塑料CLF 含氯纤维CMC 羧甲基纤维素CMCNa 羧甲基纤维素钠CMD 代尼尔纤维CMS 羧甲基淀粉COT 1,3,5-环辛四烯Cp 环戊二烯基CSA 樟脑磺酸CTAB 十六烷基三甲基溴化铵（相转移催化剂）Cy 环己基DDABCO 1，4-二氮杂双环[2.2.2]辛烷DAF 富马酸二烯丙酯DAIP 间苯二甲酸二烯丙酯DAM 马来酸二烯丙酯DAP 间苯二甲酸二烯丙酯DATBP 四溴邻苯二甲酸二烯丙酯DBA 己二酸二丁酯dba 苄叉丙酮DBE 1,2-?二溴乙烷DBEP 邻苯二甲酸二丁氧乙酯DBN 二环[5.4.0]-1,8-二氮-7-壬烯DBP 邻苯二甲酸二丁酯DBR 二苯甲酰间苯二酚DBS 癸二酸二癸酯DBU 二环[4.3.0]-1,5-二氮-5-十一烯DCC 1，3－二环己基碳化二亚胺DCCA 二氯异氰脲酸DCCK 二氯异氰脲酸钾DCCNa 二氯异氰脲酸钠DCE 1,2-二氯乙烷DCHP 邻苯二甲酸二环乙酯DCPD 过氧化二碳酸二环乙酯DDA 己二酸二癸酯DDP 邻苯二甲酸二癸酯DDQ 2,3-二氯-5，6-二氰-1，4-苯醌DEA 二乙胺DEAD 偶氮二甲酸二乙酯DEAE 二乙胺基乙基纤维素DEP 邻苯二甲酸二乙酯DETA 二乙撑三胺DFA 薄膜胶粘剂DHA 己二酸二己酯DHP 邻苯二甲酸二己酯DHS 癸二酸二己酯DIBA 己二酸二异丁酯Dibal-H 二异丁基氢化铝DIDA 己二酸二异癸酯DIDG 戊二酸二异癸酯DIDP 邻苯二甲酸二异癸酯DINA 己二酸二异壬酯DINP 邻苯二甲酸二异壬酯DINZ 壬二酸二异壬酯DIOA 己酸二异辛酯diphos(dppe) 1,2-双（二苯基膦）乙烷diphos-4(dppb) 1,2-双（二苯基膦）丁烷DMAP 4-二甲氨基吡啶DME 二甲醚DMF 二甲基甲酰胺dppf 双（二苯基膦基）二茂铁dppp 1,3-双（二苯基膦基）丙烷dvb 二乙烯苯Ee- 电解E/EA 乙烯/丙烯酸乙酯共聚物E/P 乙烯/丙烯共聚物E/P/D 乙烯/丙烯/二烯三元共聚物E/TEE 乙烯/四氟乙烯共聚物E/VAC 乙烯/醋酸乙烯酯共聚物E/VAL 乙烯/乙烯醇共聚物EAA 乙烯-丙烯酸共聚物EAK 乙基戊丙酮EBM 挤出吹塑模塑EC 乙基纤维素ECB 乙烯共聚物和沥青的共混物ECD 环氧氯丙烷橡胶ECTEE 聚（乙烯-三氟氯乙烯）ED-3 环氧酯EDA 乙二胺EDC 二氯乙烷EDTA 乙二胺四乙酸二钠EDTA 乙二胺四醋酸EE 乙氧基乙基EEA 乙烯-醋酸丙烯共聚物EG 乙二醇2-EH 异辛醇EO 环氧乙烷EOT 聚乙烯硫醚EP 环氧树脂EPI 环氧氯丙烷EPM 乙烯-丙烯共聚物EPOR 三元乙丙橡胶EPR 乙丙橡胶EPS 可发性聚苯乙烯EPSAN 乙烯-丙烯-苯乙烯-丙烯腈共聚物EPT 乙烯丙烯三元共聚物EPVC 乳液法聚氯乙烯Et 乙基EU 聚醚型聚氨酯EVA 乙烯-醋酸乙烯共聚物EVE 乙烯基乙基醚EXP 醋酸乙烯-乙烯-丙烯酸酯三元共聚乳液FF/VAL 乙烯/乙烯醇共聚物F-23 四氟乙烯-偏氯乙烯共聚物F-30 三氟氯乙烯-乙烯共聚物F-40 四氟氯乙烯-乙烯共聚物FDY 丙纶全牵伸丝FEP 全氟（乙烯-丙烯）共聚物FMN 黄素单核苷酸FNG 耐水硅胶Fp 闪点或茂基二羰基铁FPM 氟橡胶FRA 纤维增强丙烯酸酯FRC 阻燃粘胶纤维FRP 纤维增强塑料FRPA-101 玻璃纤维增强聚癸二酸癸胺（玻璃纤维增强尼龙1010树脂）FRPA-610 玻璃纤维增强聚癸二酰乙二胺（玻璃纤维增强尼龙610树脂）FVP 闪式真实热解法FWA 荧光增白剂精品文档GGF 玻璃纤维GFRP 玻璃纤维增强塑料GFRTP 玻璃纤维增强热塑性塑料促进剂GOF 石英光纤GPS 通用聚苯乙烯GR-1 异丁橡胶GR-N 丁腈橡胶GR-S 丁苯橡胶GRTP 玻璃纤维增强热塑性塑料GUV 紫外光固化硅橡胶涂料GX 邻二甲苯GY 厌氧胶Hh 小时H 乌洛托品1,5-HD 1，5－己二烯HDI 六甲撑二异氰酸酯HDPE 低压聚乙烯（高密度）HEDP 1-羟基乙叉-1，1-二膦酸HFP 六氟丙烯HIPS 高抗冲聚苯乙烯HLA 天然聚合物透明质胶HLD 树脂性氯丁胶HM 高甲氧基果胶HMC 高强度模塑料5楼HMF 非干性密封胶HMPA 六甲基磷酸三胺HMPT 六甲基磷酰胺HOPP 均聚聚丙烯HPC 羟丙基纤维素HPMC 羟丙基甲基纤维素HPMCP 羟丙基甲基纤维素邻苯二甲酸酯HPT 六甲基磷酸三酰胺HS 六苯乙烯HTPS 高冲击聚苯乙烯hv 光照IIEN 互贯网络弹性体IHPN 互贯网络均聚物IIR 异丁烯-异戊二烯橡胶IO 离子聚合物IPA 异丙醇IPN 互贯网络聚合物iPr 异丙基IR 异戊二烯橡胶IVE 异丁基乙烯基醚JJSF 聚乙烯醇缩醛胶JZ 塑胶粘合剂KKSG 空分硅胶LLAH 氢化铝锂（LiAlH4）LAS 十二烷基苯磺酸钠LCM 液态固化剂LDA 二异丙基氨基锂（有机中最重要一种大体积强碱）LDJ 低毒胶粘剂LDN 氯丁胶粘剂LDPE 高压聚乙烯（低密度）LDR 氯丁橡胶LF 脲LGP 液化石油气LHMDS 六甲基叠氮乙硅锂LHPC 低替代度羟丙基纤维素LIM 液体侵渍模塑LIPN 乳胶互贯网络聚合物LJ 接体型氯丁橡胶LLDPE 线性低密度聚乙烯LM 低甲氧基果胶LMG 液态甲烷气LMWPE 低分子量聚乙稀LN 液态氮LRM 液态反应模塑LRMR 增强液体反应模塑LSR 羧基氯丁乳胶LTBA 氢化三叔丁氧基铝锂MMA 丙烯酸甲酯MAA 甲基丙烯酸MABS 甲基丙烯酸甲酯-丙烯腈-丁二烯-苯乙烯共聚物MAL 甲基丙烯醛MBS 甲基丙烯酸甲酯-丁二烯-苯乙烯共聚物MBTE 甲基叔丁基醚MC 甲基纤维素MCA 三聚氰胺氰脲酸盐MCPA-6 改性聚己内酰胺（铸型尼龙6）mCPBA 间氯过苯酸MCR 改性氯丁冷粘鞋用胶MDI 二苯甲烷二异氰酸酯（甲撑二苯基二异氰酸酯）MDI 3，3’-二甲基-4，4’-二氨基二苯甲烷MDPE 中压聚乙烯（高密度）Me 甲基Me MethylMEK 丁酮（甲乙酮）MEKP 过氧化甲乙酮MEM 甲氧基乙氧基甲基－MES 脂肪酸甲酯磺酸盐Mes 均三甲苯基（也就是1，3，5-三甲基苯基）MF 三聚氰胺-甲醛树脂M-HIPS 改性高冲聚苯乙烯MIBK 甲基异丁基酮Min 分钟MMA 甲基丙烯酸甲酯MMF 甲基甲酰胺MNA 甲基丙烯腈MOM 甲氧甲基MPEG 乙醇酸乙酯MPF 三聚氨胺-酚醛树脂MPK 甲基丙基甲酮M-PP 改性聚丙烯MPPO 改性聚苯醚MPS 改性聚苯乙烯Ms 甲基磺酰基（保护羟基用）MS 分子筛MS 苯乙烯-甲基丙烯酸甲酯树脂MSO 石油醚MTBE 甲基叔丁基醚MTM 甲硫基甲基MTT 氯丁胶新型交联剂MWR 旋转模塑MXD-10/6 醇溶三元共聚尼龙MXDP 间苯二甲基二胺NNaphth 萘基NBD 二环庚二烯（别名：降冰片二烯）NBR 丁腈橡胶NBS N-溴代丁二酰亚胺?别名：N-溴代琥珀酰亚胺NCS N-氯代丁二酰亚胺.?别名：N-氯代琥珀酰亚胺NDI 二异氰酸萘酯NDOP 邻苯二甲酸正癸辛酯NHDP 邻苯二甲酸己正癸酯NHTM 偏苯三酸正己酯Ni(R) 雷尼镍（氢活性催化还原剂）NINS 癸二酸二异辛酯NLS 正硬脂酸铅NMO N-甲基氧化吗啉NMP N-甲基吡咯烷酮NODA 己二酸正辛正癸酯NODP 邻苯二甲酸正辛正癸酯NPE 壬基酚聚氧乙烯醚NR 天然橡胶OOBP 邻苯二甲酸辛苄酯ODA 己二酸异辛癸酯ODPP 磷酸辛二苯酯OIDD 邻苯二甲酸正辛异癸酯精品文档OPP 定向聚丙烯（薄膜）OPS 定向聚苯乙烯（薄膜）OPVC 正向聚氯乙烯OT 气熔胶PPA 聚酰胺（尼龙）PA-1010 聚癸二酸癸二胺（尼龙1010）PA-11 聚十一酰胺（尼龙11）PA-12 聚十二酰胺（尼龙12）PA-6 聚己内酰胺（尼龙6）PA-610 聚癸二酰乙二胺（尼龙610）PA-612 聚十二烷二酰乙二胺（尼龙612）PA-66 聚己二酸己二胺（尼龙66）PA-8 聚辛酰胺（尼龙8）PA-9 聚9-氨基壬酸（尼龙9）PAA 聚丙烯酸PAAS 水质稳定剂PABM 聚氨基双马来酰亚胺PAC 聚氯化铝PAEK 聚芳基醚酮PAI 聚酰胺-酰亚胺6楼PAM 聚丙烯酰胺PAMBA 抗血纤溶芳酸PAMS 聚α－甲基苯乙烯PAN 聚丙烯腈PAP 对氨基苯酚PAPA 聚壬二酐PAPI 多亚甲基多苯基异氰酸酯PAR 聚芳酯（双酚A型）PAR 聚芳酰胺PAS 聚芳砜（聚芳基硫醚）PB 聚丁二烯-〔1，3]PBAN 聚（丁二烯-丙烯腈）PBI 聚苯并咪唑PBMA 聚甲基丙烯酸正丁酯PBN 聚萘二酸丁醇酯PBS 聚（丁二烯-苯乙烯）PBT 聚对苯二甲酸丁二酯PC 聚碳酸酯PC/ABS 聚碳酸酯/ABS树脂共混合金PC/PBT 聚碳酸酯/聚对苯二甲酸丁二醇酯弹性体共混合金PCC 吡啶氯铬酸盐PCD 聚羰二酰亚胺PCDT 聚（1，4-环己烯二亚甲基对苯二甲酸酯）PCE 四氯乙烯PCMX 对氯间二甲酚PCT 聚己内酰胺PCT 聚对苯二甲酸环己烷对二甲醇酯PCTEE 聚三氟氯乙烯PD 二羟基聚醚PDAIP 聚间苯二甲酸二烯丙酯PDAP 聚对苯二甲酸二烯丙酯PDC 重铬酸吡啶PDMS 聚二甲基硅氧烷PEG 聚乙二醇Ph 苯基PhH 苯PhMe 甲苯Phth 邻苯二甲酰Pip 哌啶基Pr n-丙基Py 吡啶Qquant. 定量产率RRE 橡胶粘合剂Red-Al [（MeOCH2CH2O）AlH2]NaRF 间苯二酚-甲醛树脂RFL 间苯二酚-甲醛乳胶RP 增强塑料RP/C 增强复合材料RX 橡胶软化剂SS/MS 苯乙烯-α-甲基苯乙烯共聚物SAN 苯乙烯-丙烯腈共聚物SAS 仲烷基磺酸钠SB 苯乙烯-丁二烯共聚物SBR 丁苯橡胶SBS 苯乙烯-丁二烯-苯乙烯嵌段共聚物sBu 仲丁基sBuLi 仲丁基锂SC 硅橡胶气调织物膜SDDC N，N-二甲基硫代氨基甲酸钠SE 磺乙基纤维素SGA 丙烯酸酯胶SI 聚硅氧烷Siamyl 二异戊基SIS 苯乙烯-异戊二烯-苯乙烯嵌段共聚物SIS/SEBS 苯乙烯-乙烯-丁二烯-苯乙烯共聚物SM 苯乙烯SMA 苯乙烯-顺丁烯二酸酐共聚物SPP 间规聚苯乙烯SPVC 悬浮法聚氯乙烯SR 合成橡胶ST 矿物纤维TTAC 三聚氰酸三烯丙酯TAME 甲基叔戊基醚TAP 磷酸三烯丙酯TASF 三（二乙胺基）二氟三甲基锍硅酸盐TBAF 氟化四丁基铵TBDMS,?TBS 叔丁基二甲基硅烷基（羟基保护基）TBE 四溴乙烷TBHP 过氧叔丁醇TBP 磷酸三丁酯t-Bu 叔丁基TCA 三醋酸纤维素TCCA 三氯异氰脲酸TCF 磷酸三甲酚酯TCPP 磷酸三氯丙酯TDI 甲苯二异氰酸酯TEA 三乙胺TEAE 三乙氨基乙基纤维素TEBA 三乙基苄基胺TEDA 三乙二胺TEFC 三氟氯乙烯TEMPO 四甲基氧代胡椒联苯自由基TEP 磷酸三乙酯Tf?or?OTf 三氟甲磺酸TFA 三氟乙酸TFAA 三氟乙酸酐TFE 四氟乙烯THF 四氢呋喃THF 四氢呋喃THP 四氢吡喃基TLCP 热散液晶聚酯TMEDA 四甲基乙二胺TMP 三羟甲基丙烷TMP 2,2,6,6-四甲基哌啶TMPD 三甲基戊二醇TMS 三甲基硅烷基TMTD 二硫化四甲基秋兰姆（硫化促进剂TT）TNP 三壬基苯基亚磷酸酯Tol 甲苯基TPA 对苯二甲酸TPE 磷酸三苯酯TPS 韧性聚苯乙烯TPU 热塑性聚氨酯树脂Tr 三苯基TR 聚硫橡胶TRIS 三异丙基乙磺酰TRPP 纤维增强聚丙烯TR-RFT 纤维增强聚对苯二甲酸丁二醇酯TRTP 纤维增强热塑性塑料Ts?(Tos) 对甲苯磺酰基UU 脲UF 脲甲醛树脂UHMWPE 超高分子量聚乙烯UP 不饱和聚酯VVAC 醋酸乙烯酯VAE 乙烯-醋酸乙烯共聚物VAM 醋酸乙烯VAMA 醋酸乙烯-顺丁烯二酐共聚物VC 氯乙烯VC/CDC 氯乙烯/偏二氯乙烯共聚物VC/E 氯乙烯/乙烯共聚物VC/E/MA 氯乙烯/乙烯/丙烯酸甲酯共聚物VC/E/VAC 氯乙烯/乙烯/醋酸乙烯酯共聚物VC/MA 氯乙烯/丙烯酸甲酯共聚物VC/MMA 氯乙烯/甲基丙烯酸甲酯共聚物VC/OA 氯乙烯/丙烯酸辛酯共聚物VC/VAC 氯乙烯/醋酸乙烯酯共聚物VCM 氯乙烯（单体）VCP 氯乙烯-丙烯共聚物VCS 丙烯腈-氯化聚乙烯-苯乙烯共聚物VDC 偏二氯乙烯VPC 硫化聚乙烯VTPS 特种橡胶偶联剂WWF 新型橡塑填料WP 织物涂层胶WRS 聚苯乙烯球形细粒XXF 二甲苯-甲醛树脂XMC 复合材料YYH 改性氯丁胶YM 聚丙烯酸酯压敏胶乳YWG 液相色谱无定型微粒硅胶ZZE 玉米纤维ZH 溶剂型氯化天然橡胶胶粘剂ZN 粉状脲醛树脂胶。

copper centers(Cu A and Cu B)and two hemes—low-spin heme a and high-spin heme a3.Despite many years of research,the individual absolute absorption spectra of the two hemes in the Soret band(420–460nm)have not yet been resolved because they overlap strongly. There is but a single classical work of Vanneste[1]reporting the absolute individual spectra of the reduced hemes a and a3.We revisited the problem with new approaches as summarized below.(1)Calcium binding to mitochondrial COX induces a small red shift of the absorption spectrum of heme a.Treating the calcium-induced difference spectrum as thefirst derivative(differential)of the ab-sorption spectrum of the reduced heme a,it is possible to reconstruct the line shape of the parent absolute spectrum of a2+by integration. The Soret band absolute spectrum of the reduced heme a obtained in this way differs strongly form that in ref.[1].It is fairly symmetric and can be easily approximated by two10nm Gaussians with widely split maxima at442and451nm.In contrast to Vanneste,no evidence for the~428nm shoulder is observed for heme a2+.(2)The overall Soret band of the reduced COX reveals at least5 more Gaussians that are not affected by Ca2+.Two of them at436 and443nm can be attributed to electronic B0transitions in heme a3, and two more can represent their vibronic satellites.(3)A theoretical dipole–dipole interaction model was developed [2]for calculation of absorption and CD spectra.The model allows to optimize parameters of the B x,y electronic transitions in the hemes a and a3to obtain bestfit to the experimental spectra.The optimized parameters agree with the characteristics of the reconstructed spectra of hemes a and a3.References[1]W.H.Vanneste,The stoichiometry and absorption spectra ofcomponents a and a-3in cytochrome c oxidase,Biochemistry,5 (1966)838–48.[2]A.V.Dyuba,A.M.Arutyunyan,T.V.Vygodina,N.V.Azarkina,A.V.Kalinovich,Y.A.Sharonov,and A.A.Konstantinov,Circular dichroism of cytochrome c oxidase,Metallomics,3(2011),417–432.doi:10.1016/j.bbabio.2014.05.171S9.P8Flavodiiron enzymes as oxygen and/or nitric oxide reductases Vera Gonçalves a,b,João B.Vicente b,c,Liliana Pinto a,Célia V.Romão a, Carlos Frazão a,Paolo Sarti d,e,f,Alessandro Giuffrèf,Miguel Teixeira a a Instituto de Tecnologia Química e Biológica António Xavier,Universidade Nova de Lisboa,Av.da República,2781–901Oeiras,Portugalb Metabolism and Genetics Group,Institute for Medicines and Pharmaceutical Sciences(iMed.UL),Faculty of Pharmacy,University of Lisbon,Av.Prof.Gama Pinto,1649–003Lisboa,Portugalc Department of Biochemistry and Human Biology,Faculty of Pharmacy, University of Lisbon,Av.Prof.Gama Pinto,1649-003Lisboa,Portugald Department of Biochemical Sciences,Sapienza University of Rome,Piazzale Aldo Moro5,I-00185Rome,Italye Fondazione Cenci Bolognetti—Istituto Pasteur,Italyf Institute of Biology,Molecular Medicine and Nanobiotechnology,National Research Council of Italy(CNR),ItalyE-mail:**************.ptThe Flavodiiron proteins(FDPs)are present in all life domains, from unicellular microbes to higher eukaryotes.FDPs reduce oxygen to water and/or nitrous oxide to nitrous oxide,actively contributing to combat the toxicity of O2or NO.The catalytic ability of FDPs is comparable to that of bonafide heme–copper/iron O2/NO transmem-brane reductases.FDPs are multi-modular water soluble enzymes, exhibiting a two-domain catalytic core,whose the minimal functional unit is a‘head-to-tail’homodimer,each monomer being built by a beta-lactamase domain harbouring a diiron catalytic site,and a short-chainflavodoxin,binding FMN[1–3].Despite extensive data collected on FDPs,the molecular determi-nants defining their substrate selectivity remain unclear.To clarify this issue,two FDPs with known and opposite substrate preferences were analysed and compared:the O2-reducing FDP from the eukaryote Entamoeba histolytica(EhFdp1)and the NO reductase FlRd from Escherichia coli.While the metal ligands are strictly conserved in these two enzymes,differences near the active site were observed.Single and double mutants of the EhFdp1were produced by replacing the residues in these positions with their equivalent in the E.coli FlRd.The biochemical and biophysical features of the EhFdp1WT and mutants were studied by potentiometric-coupled spectroscopic methods(UV–visible and EPR spectroscopies).The O2/NO reactivity was analysed by amperometric methods and stopped-flow absorption spectroscopy.The reactivity of the mutants towards O2was negatively affected, while their reactivity with NO was enhanced.These observations suggest that the residues mutated have a role in defining the substrate selectivity and reaction mechanism.References[1]C.Frazao,G.Silva,C.M.Gomes,P.Matias,R.Coelho,L.Sieker,S.Macedo,M.Y.Liu,S.Oliveira,M.Teixeira,A.V.Xavier,C.Rodrigues-Pousada,M.A.Carrondo,J.Le Gall,Structure of a dioxygen reduction enzyme from Desulfovibrio gigas,Nature Structural Biology,7(2000)1041–1045.[2]J.B.Vicente,M.A.Carrondo,M.Teixeira,C.Frazão,FlavodiironProteins:Nitric Oxide and/or Oxygen Reductases,in:Encyclopedia of Inorganic and Bioinorganic Chemistry,(2011).[3]V.L.Gonçalves,J.B.Vicente,L.M.Saraiva,M.Teixeira,FlavodiironProteins and their role in cyanobacteria,in: C.Obinger,G.A.Peschek(Eds.)Bioenergetic Processes of Cyanobacteria,Springer Verlag,(2011),pp.631–656.doi:10.1016/j.bbabio.2014.05.172S9.P9CydX is a subunit of Escherichia coli cytochrome bd terminal oxidase and essential for assembly and stability of the di-heme active siteJo Hoeser a,Gerfried Gehmann a,Robert B.Gennis b,Thorsten Friedrich ca Institut für Biochemie/Uni Freiburg,Germanyb Department of Biochemistry,University of Illinois at Urbana Champaign, USAc Albert-Ludwigs-Universitat Freiburg,GermanyE-mail:*****************.uni-freiburg.deThe cytochrome bd ubiquinol oxidase is part of many prokaryotic respiratory chains.It catalyzes the oxidation of ubiquinol to ubiqui-none while reducing molecular oxygen to water.The reaction is coupled to the vectorial transfer of1H+/e−across the membrane, contributing to the proton motive force essential for energy consum-ing processes.The presence of this terminal oxidase is known to be related to the virulence of several human pathogens,making it a very attractive drug target.The three heme groups of the oxidase are presumably located in subunit CydA.Heme b558is involved in ubiquinol oxidation,while the reduction of molecular oxygen is catalyzed by a di-nuclear heme center containing hemes b595and d [1].A severe change in Escherichia coli phenotype was noticed when a 111nt gene,denoted as cydX and located at the5′end of the cyd operon,was deleted.This small gene codes for a single transmem-brane helix obviously needed for the activity of the oxidase[2].WeAbstracts e98overproduced the terminal oxidase with and without the cydX gene product.The resulting enzyme was purified by chromatographic steps and the cofactors were spectroscopically characterized.We demon-strated that CydX tightly binds to the CydAB complex and is co-purified.The identity of CydX was determined by mass spectrometry. Additionally,the di-heme active site was only detectable in the variant containing CydX.Thus,CydX is the third subunit of the E.coli bd oxidase and is essential for the assembly and stability of the di-heme site[3].References[1]V.B.Borisov,R.B.Gennis,J.Hemp,M.I.Verkhovsky,The cytochromebd respiratory oxygen reductases,Biochim.Biophys.Acta.1807 (2011)1398–1413./10.1016/j.bbabio.2011.06.016.[2]C.E.VanOrsdel,S.Bhatt,R.J.Allen,E.P.Brenner,J.J.Hobson,A.Jamil,et al.,The Escherichia coli CydX protein is a member of the CydAB cytochrome bd oxidase complex and is required for cytochrome bd oxidase activity,J.Bacteriol.195(2013)3640–3650./10.1128/JB.00324-13.[3]J.Hoeser,S.Hong,G.Gehmann,R.B.Gennis,T.Friedrich,SubunitCydX of Escherichia coli cytochrome bd ubiquinol oxidase is essential for assembly and stability of the di-heme active site,FEBS Lett.(2014)./10.1016/j.febslet.2014.03.036.doi:10.1016/j.bbabio.2014.05.173S9.P10Characterization of the two cbb3-type cytochrome c oxidase isoforms from Pseudomonas stutzeri ZoBellMartin Kohlstaedt a,Hao Xie a,Sabine Buschmann a,Anja Resemann b, Julian nger c,Hartmut Michel ca MPI of Biophysics,Germanyb Bruker Daltonik GmbH,Germanyc Max-Planck-Institute of Biophysics,Department of Molecular Membrane Biology,GermanyE-mail:*****************************.deCytochrome c oxidases(CcOs)are the terminal enzymes of the respiratory chain and are members of the heme-copper oxidase superfamily(HCO).CcOs catalyze the reduction of molecular O2to water and couple this exergonic reaction with transmembrane proton pared to family A and B CcOs,the cbb3-type CcOs which represent the C-family,feature a distinctly different subunit composition,a reduced proton pumping stoichiometry and higher catalytic activity at low oxygen concentrations[1][2].The genome of Pseudomonas stutzeri ZoBell contains two independent cbb3-operons, encoding Cbb3-1(CcoNOP)and Cbb3-2(CcoNOQP).We generated variants with a focus on ccoQ whose function is unknown.The purified variants and the wildtype Cbb3were analyzed using UV–vis spec-troscopy,BN-and SDS-PAGE,O2reductase activity(ORA)and immunoblotting with an antibody specific for CcoQ.We found that the deletion of ccoQ has an influence on a b-type heme in the binuclear center,and that both the stability and the ORA are decreased without ccoQ compared to the WT.The O2affinity(OA)of Cbb3was spec-trophotometrically determined with oxygenated leghemoglobin as an O2delivery system.The determined Km values for the recombinant Cbb3-1are similar to previously published data[2].The Km value of rec.Cbb3-2is about2-fold higher than the value of rec.Cbb3-1.In addition,the OA and ORA of different variants introduced into the O2-cavity of rec.Cbb3-1show significant differences compared to the WT. In the structure of Cbb3,an additional transmembraneαhelix was detected but so far not assigned to any protein[3].We sequenced and identified the polypeptide chain using a customized MALDI-Tandem-MS-based setup and found a putative protein.The amino acid sequence of this proteinfits the electron density of the unknown helix and we are currently investigating the functional relevance of this protein.References[1]RS.Pitcher,NJ.Watmough The bacterial cytochrome cbb3oxidaseBiochim Biophys Acta,1655(2004),pp.388–399[2]O.Preisig,R.Zufferey,L.Thöny-Meyer,C.A.Appleby,H.HenneckeA high-affinity cbb3-type cytochrome oxidase terminates thesymbiosis-specific respiratory chain of Bradyrhizobium japonicum J.Bacteriol,178(1996),pp.1532–1538[3]S.Buschmann,E.Warkentin,H.Xie,nger,U.Ermler,H.MichelThe structure of cbb3cytochrome oxidase provides insights into proton pumping Science,329(2010),pp.327–330.doi:10.1016/j.bbabio.2014.05.174S9.P11Expression of terminal oxidases under nutrient-limited conditions in Shewanella oneidensis MR-1Sébastien Le Laz a,Arlette Kpebe b,Marielle Bauzan c,Sabrina Lignon d, Marc Rousset a,Myriam Brugna aa BIP,CNRS,Marseille,Franceb BIP,CNRS/AMU,Francec CNRS,Aix-Marseille Université,Unitéde fermentation,FR3479,IMM, Franced CNRS,Aix-Marseille Université,Plate-forme Protéomique,FR3479,IMM, MaP IBiSA,FranceE-mail:***************.frShewanella species are facultative anaerobic bacteria renowned for their remarkable respiratory versatility that allows them to use,in addition to O2,a broad spectrum of compounds as electron acceptors. In the aerobic respiratory chain,terminal oxidases catalyze the last electron transfer step by reducing molecular oxygen to water.The genome of Shewanella oneidensis MR-1encodes for three terminal oxidases:a bd-type quinol oxidase and two heme-copper oxidases, a A-type cytochrome c oxidase(Cox)and a cbb3-type oxidase.In a previous study,we investigate the role of these terminal oxidases under aerobic and microaerobic conditions in rich medium using a biochemical approach[1].Our results revealed the particularity of the aerobic respiratory pathway in S.oneidensis since the cbb3-type oxidase was the predominant oxidase under aerobic conditions while the bd-type and the cbb3-type oxidases were involved in respira-tion at low-O2tensions.Against all expectation,the low-affinity Cox oxidase had no physiological significance in our experimental conditions.Do these data reflect a functional loss of Cox resulting from evolutionary mechanisms as suggested by Zhou et al.[2]?Is Cox expressed under specific conditions like the aa3oxidase in Pseudo-monas aeruginosa,maximally expressed under starvation conditions [3]?To address these questions,we investigated the expression pattern of the terminal oxidases under nutrient-limited conditions and different dissolved O2tensions by measuring oxidase activities coupled to mass-spectrometry analysis.In addition to the notable modulation of the expression of the bd-type and cbb3-type oxidases in the different tested conditions,we detected Cox oxidase under carbon-starvation conditions.This constitutes thefirst report of a condition under which the A-type oxidase is expressed in S.oneidensis. We suggest that Cox may be crucial for energy conservation in carbon-limited environments and we propose that Cox may be a component of a general protective response against oxidative stress allowing S.oneidensis to thrive under highly aerobic habitats.Abstracts e99。

Quality evaluation of Flos Lonicerae through a simultaneous determination of seven saponins by HPLC with ELSDXing-Yun Chai1, Song-Lin Li2, Ping Li1*1Key Laboratory of Modern Chinese Medicines and Department of Pharmacognosy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China2Institute of Nanjing Military Command for Drug Control, Nanjing, 210002, People’s Republic of China*Corresponding author: Ping LiKey Laboratory of Modern Chinese Medicines and Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210009, People’s Republic of China.E-mail address: lipingli@Tel.: +86-25-8324-2299; 8539-1244; 135********Fax: +86-25-8532-2747AbstractA new HPLC coupled with evaporative light scattering detection (ELSD) method has been developed for the simultaneous quantitative determination of seven major saponins, namely macranthoidinB (1), macranthoidin A (2), dipsacoside B (3), hederagenin-28-O-β-D-glucopyranosyl(6→1)-O-β-D- glucopyranosyl ester (4), macranthoside B (5), macranthoside A (6), and hederagenin-3-O-α-L-arabinopyranosyl(2→1)-O-α-L-rhamnopyranoside (7)in Flos Lonicerae, a commonly used traditional Chinese medicine (TCM) herb.Simultaneous separation of these seven saponins was achieved on a C18 analytical column with a mixed mobile phase consisting of acetonitrile(A)-water(B)(29:71 v/v) acidified with 0.5% acetic acid. The elution was operated from keeping 29%A for 10min, then gradually to 54%B from 10 to 25 min on linear gradient, and then keep isocratic elution with 54%B from 25 to 30min.The drift tube temperature of ELSD was set at 106℃, and with the nitrogen flow-rate of 2.6 l/min. All calibration curves showed good linear regression (r2 0.9922) within test ranges. This method showed good reproducibility for the quantification of these seven saponins in Flos Lonicerae with intra- and inter-day variations of less than 3.0% and 6.0% respectively. The validated method was successfully applied to quantify seven saponins in five sources of Flos Lonicerae, which provides a new basis of overall assessment on quality of Flos Lonicerae.Keywords: HPLC-ELSD; Flos Lonicerae; Saponins; Quantification1. IntroductionFlos Lonicerae (Jinyinhua in Chinese), the dried buds of several species of the genus Lonicera (Caprifoliaceae), is a commonly used traditional Chinese medicine (TCM) herb. It has been used for centuries in TCM practice for the treatment of sores, carbuncles, furuncles, swelling and affections caused by exopathogenic wind-heat or epidemic febrile diseases at the early stage [1]. Though four species of Lonicera are documented as the sources of Flos Lonicerae in China Pharmacopeia (2000 edition), i.e. L. japonica, L. hypoglauca,L. daystyla and L. confusa, other species such as L. similes and L. macranthoides have also been used on the same purpose in some local areas in China [2]. So it is an important issue to comprehensively evaluate the different sources of Flos Lonicerae, so as to ensure the clinical efficacy of this Chinese herbal drug.Chemical and pharmacological investigations on Flos Lonicerae resulted in discovering several kinds of bioactive components, i.e. chlorogenic acid and its analogues, flavonoids, iridoid glucosides and triterpenoid saponins [3]. Previously, chlorogenic acid has been used as the chemical marker for the quality evaluation of Flos Lonicerae,owing to its antipyretic and antibiotic property as well as its high content in the herb. But this compound is not a characteristic component of Flos Lonicerae, as it has also been used as the chemical marker for other Chinese herbal drugs such as Flos Chrysanthemi and so on[4-5]. Moreover, chlorogenic acid alone could not be responsible for the overall pharmacological activities of Flos Lonicerae[6].On the other hand, many studies revealed that triterpenoidal saponins of Flos Lonicerae possess protection effects on hepatic injury caused by Acetaminophen, Cd, and CCl4, and conspicuous depressant effects on swelling of ear croton oil [7-11]. Therefore, saponins should also be considered as one of the markers for quality control of Flos Lonicerae. Consequently, determinations of all types of components such as chlorogenic acid, flavonoids, iridoid glucosides and triterpenoidal saponins in Flos Lonicerae could be a better strategy for the comprehensive quality evaluation of Flos Lonicerae.Recently an HPLC-ELSD method has been established in our laboratory for qualitative and quantitative determination of iridoid glucosides in Flos Lonicerae [12]. But no method was reported for the determination of triterpenoidal saponins in Flos Lonicera. As a series studies on the comprehensive evaluation of Flos Lonicera, we report here, for the first time, the development of an HPLC-ELSD method for simultaneous determination of seven triterpenoidal saponins in the Chinese herbal drug Flos Lonicerae, i.e.macranthoidin B (1), macranthoidin A (2), dipsacoside B (3), hederagenin-28-O-β-D-glucopyranosyl(6→1)-O-β-D- glucopyranosyl ester (4), macranthoside B (5), macranthoside A (6), and hederagenin-3-O-α-L-arabinopyranosyl(2→1)-O-α-L-rhamnopyranoside (7) (Fig. 1).2. Experimental2.1. Samples, chemicals and reagentsFive samples of Lonicera species,L. japonica from Mi county, HeNan province (LJ1999-07), L. hypoglauca from Jiujang county, JiangXi province (LH2001-06), L. similes from Fei county, ShanDong province (LS2001-07), L. confuse from Xupu county, HuNan province (LC2001-07), and L. macranthoides from Longhu county, HuNan province (LM2000-06) respectively, were collected in China. All samples were authenticated by Dr. Ping Li, professor of department of Pharmacognosy, China Pharmaceutical University, Nanjing, China. The voucher specimens were deposited in the department of Pharmacognosy, China Pharmaceutical University, Nanjing, China. Seven saponin reference compounds: macranthoidin B (1), macranthoidin A (2), dipsacoside B (3), hederagenin-28-O-β-D-glucopyranosyl(6→1)-O-β-D- glucopyranosyl ester (4), macranthoside B (5), macranthoside A (6), and hederagenin-3-O-α-L-arabinopyranosyl(2→1)-O-α-L-rhamnopyranoside (7) were isolated previously from the dried buds of L. confusa by repeated silica gel, sephadex LH-20 and Rp-18 silica gel column chromatography, their structures were elucidated by comparison of their spectral data (UV, IR, MS, 1H- NMR and 13C-NMR) with references [13-15]. The purity of these saponins were determined to be more than 98% by normalization of the peak areas detected by HPLC with ELSD, and showed very stable in methanol solution.HPLC-grade acetonitrile from Merck (Darmstadt, Germany), the deionized water from Robust (Guangzhou, China), were purchased. The other solvents, purchased from Nanjing Chemical Factory (Nanjing, China) were of analytical grade.2.2. Apparatus and chromatographic conditionsAglient1100 series HPLC apparatus was used. Chromatography was carried out on an Aglient Zorbax SB-C18 column（250 4.6mm, 5.0µm）at a column temperature of 25℃.A Rheodyne 7125i sampling valve (Cotati, USA) equipped with a sample loop of 20µl was used for sample injection. The analog signal from Alltech ELSD 2000 (Alltech, Deerfield, IL, USA)was transmitted to a HP Chemstation for processing through an Agilent 35900E (Agilent Technologies, USA).The optimum resolution was obtained by using a linear gradient elution. The mobile phase was composed of acetonitrile(A) and water(B) which acidified with 0.5% acetic acid. The elution was operated from keeping 29%A for 10min, then gradually to 54%B from 10 to 25 min in linear gradient, and back to the isocratic elution of 54%B from 25 to 30 min.The drift tube temperature for ELSD was set at 106℃and the nitrogen flow-rate was of 2.6 l/min. The chromatographic peaks were identified by comparing their retention time with that of each reference compound tried under the same chromatographic conditions with a series of mobile phases. In addition, spiking samples with the reference compounds further confirmed the identities of the peaks.2.3. Calibration curvesMethanol stock solutions containing seven analytes were prepared and diluted to appropriate concentration for the construction of calibration curves. Six concentrationof the seven analytes’ solution were injected in triplicate, and then the calibration curves were constructed by plotting the peak areas versus the concentration of each analyte. The results were demonstrated in Table1.2.4. Limits of detection and quantificationMethanol stock solution containing seven reference compounds were diluted to a series of appropriate concentrations with methanol, and an aliquot of the diluted solutions were injected into HPLC for analysis.The limits of detection (LOD) and quantification (LOQ) under the present chromatographic conditions were determined at a signal-to-noise ratio (S/N) of 3 and 10, respectively. LOD and LOQ for each compound were shown in Table1.2.5. Precision and accuracyIntra- and inter-day variations were chosen to determine the precision of the developed assay. Approximate 2.0g of the pulverized samples of L. macranthoides were weighted, extracted and analyzed as described in 2.6 Sample preparation section. For intra-day variability test, the samples were analyzed in triplicate for three times within one day, while for inter-day variability test, the samples were examined in triplicate for consecutive three days. Variations were expressed by the relative standard deviations. The results were given in Table 2.Recovery test was used to evaluate the accuracy of this method. Accurate amounts of seven saponins were added to approximate 1.0g of L. macranthoides,and then extracted and analyzed as described in 2.6 Sample preparation section. The average recoveries were counted by the formula: recovery (%) = (amount found –original amount)/ amount spiked ×100%, and RSD (%) = (SD/mean) ×100%. The results were given in Table 3.2.6. Sample preparationSamples of Flos Lonicerae were dried at 50℃until constant weight. Approximate 2.0g of the pulverized samples, accurately weighed, was extracted with 60% ethanol in a flask for 4h. The ethanol was evaporated to dryness with a rotary evaporator. Residue was dissolved in water, followed by defatting with 60ml of petroleum ether for 2 times, and then the water solution was evaporated, residue was dissolved with methanol into a 25ml flask. One ml of the methanol solution was drawn and transferred to a 5ml flask, diluted to the mark with methanol. The resultant solution was at last filtrated through a 0.45µm syringe filter (Type Millex-HA, Millipore, USA) and 20µl of the filtrate was injected to HPLC system. The contents of the analytes were determined from the corresponding calibration curves.3. Results and discussionsThe temperature of drift tube and the gas flow-rate are two most important adjustable parameters for ELSD, they play a prominent role to an analyte response. In ourprevious work [12], the temperature of drift tube was optimized at 90°C for the determination of iridoids. As the polarity of saponins are higher than that of iridoids, more water was used in the mobile phase for the separation of saponins, therefore the temperature for saponins determination was optimized systematically from 95°C to 110°C, the flow-rate from 2.2 to 3.0 l/min. Dipsacoside B was selected as the testing saponin for optimizing ELSD conditions, as it was contained in all samples. Eventually, the drift tube temperature of 106℃and a gas flow of 2.6 l/min were optimized to detect the analytes. And these two exact experimental parameters should be strictly controlled in the analytical procedure [16].All calibration curves showed good linear regression (r2 0.9922) within test ranges. Validation studies of this method proved that this assay has good reproducibility. As shown in Table 2, the overall intra- and inter-day variations are less than 6% for all seven analytes. As demonstrated in Table 3, the developed analytical method has good accuracy with the overall recovery of high than 96% for the analytes concerned. The limit of detection (S/N=3) and the limit of quantification (S/N=10) are less than 0.26μg and 0.88μg respectively (Table1), indicating that this HPLC-ELSD method is precise, accurate and se nsitive enough for the quantitative evaluation of major non- chromaphoric saponins in Flos Lonicerae.It has been reported that there are two major types of saponins in Flos Lonicerae, i.e. saponins with hederagenin as aglycone and saponins with oleanolic acid as the aglycone [17]. But hederagenin type saponins of the herb were reported to have distinct activities of liver protection and anti-inflammatory [7-11]. So we adoptedseven hederagenin type saponins as representative markers to establish a quality control method.The newly established HPLC-ELSD method was applied to analyze seven analytes in five plant sources of Flos Lonicerae, i.e. L. japonica,L. hypoglauca,L. confusa,L. similes and L. macranthoides(Table 4). It was found that there were remarkable differences of seven saponins contents between different plant sources of Flos Lonicerae. All seven saponins analyzed could be detected in L. confusa and L. hypoglauca, while only dipsacoside B was detected in L. japonica. Among all seven saponins interested, only dipsacoside B was found in all five plant species of Flos Lonicerae analyzed, and this compound was determined as the major saponin with content of 53.7 mg/g in L. hypoglauca. On the other hand, macranthoidin B was found to be the major saponin with the content higher than 41.0mg/g in L. macranthoides,L. confusa, and L. similis, while the contents of other analytes were much lower.In our previous study [12], overall HPLC profiles of iridoid glucosides was used to qualitatively and quantitatively distinguish different origins of Flos Lonicerae. As shown in Fig.2, the chromatogram profiles of L. confusa, L. japonica and L. similes seem to be similar, resulting in the difficulty of clarifying the origins of Flos Lonicerae solely by HPLC profiles of saponins, in addition to the clear difference of the HPLC profiles of saponins from L. macranthoides and L. hypoglauca.Therefore, in addition to the conventional morphological and histological identification methods, the contents and the HPLC profiles of saponins and iridoids could also be used as accessory chemical evidence toclarify the botanical origin and comprehensive quality evaluation of Flos Lonicerae.4. ConclusionsThis is the first report on validation of an analytical method for qualification and quantification of saponins in Flos Lonicerae. This newly established HPLC-ELSD method can be used to simultaneously quantify seven saponins, i.e. macranthoidin B, macranthoidin A, dipsacoside B, hederagenin-28-O-β-D-glucopyranosyl(6→1)-O-β-D- glucopyranosyl ester, macranthoside B, macranthoside A, and hederagenin-3-O-α-L-arabinopyranosyl(2→1)-O-α-L-rhamnopyranoside in Flos Lonicerae. Together with the HPLC profiles of iridoids, the HPLC-ELSD profiles of saponins could also be used as an accessory chemical evidence to clarify the botanical origin and comprehensive quality evaluation of Flos Lonicerae.AcknowledgementsThis project is financially supported by Fund for Distinguished Chinese Young Scholars of the National Science Foundation of China (30325046) and the National High Tech Program（2003AA2Z2010）.[1]Ministry of Public Health of the People’s Republic of China, Pharmacopoeia ofthe People’s Republic of China, V ol.1, 2000, p. 177.[2]W. Shi, R.B. Shi, Y.R. Lu, Chin. Pharm. J., 34(1999) 724.[3]J.B. Xing, P. Li, D.L. Wen, Chin. Med. Mater., 26(2001) 457.[4]Y.Q. Zhang, L.C. Xu, L.P. Wang, J. Chin. Med. Mater., 21(1996) 204.[5] D. Zhang, Z.W. Li, Y. Jiang, J. Pharm. Anal., 16(1996) 83.[6]T.Z. Wang, Y.M. Li, Huaxiyaoxue Zazhi, 15(2000) 292.[7]J.ZH. Shi, G.T. Liu. Acta Pharm. Sin., 30(1995) 311.[8]Y. P. Liu, J. Liu, X.SH. Jia, et al. Acta Pharmacol. Sin., 13 (1992) 209.[9]Y. P. Liu, J. Liu, X.SH. Jia, et al. Acta Pharmacol. Sin., 13 (1992) 213.[10]J.ZH. Shi, L. Wan, X.F. Chen.ZhongYao YaoLi Yu LinChuang, 6 (1990) 33.[11]J. Liu, L. Xia, X.F. Chen. Acta Pharmacol. Sin., 9 (1988) 395[12]H.J. Li, P. Li, W.C. Ye, J. Chromatogr. A 1008(2003) 167-72.[13]Q. Mao, D. Cao, X.SH. Jia. Acta Pharm. Sin., 28(1993) 273.[14]H. Kizu, S. Hirabayashi, M. Suzuki, et al. Chem. Pharm. Bull., 33(1985) 3473.[15]S. Saito, S. Sumita, N. Tamura, et al. Chem Pharm Bull., 38(1990) 411.[16]Alltech ELSD 2000 Operating Manual, Alltech, 2001, p. 16. In Chinese.[17]J.B. Xing, P. Li, Chin. Med. Mater., 22(1999) 366.Fig. 1 Chemical structures of seven saponins from Lonicera confusa macranthoidin B (1), macranthoidin A (2), dipsacoside B (3), hederagenin-28-O-β-D-glucopyranosyl(6→1)-O-β-D- glucopyranosyl ester (4), macranthoside B (5), macranthoside A (6), and hederagenin-3-O-α-L-arabinopyranosyl(2→1)-O-α-L-rhamnopyranoside (7)Fig. 2Representative HPLC chromatograms of mixed standards and methanol extracts of Flos Lonicerae.Column: Agilent Zorbax SB-C18 column（250 4.6mm, 5.0µm）, temperature of 25℃; Detector: ELSD, drift tube temperature 106℃, nitrogen flow-rate 2.6 l/min.A: Mixed standards, B: L. confusa, C: L. japonica, D: L. macranthoides, E: L. hypoglauca, F: L. similes.Table 1 Calibration curves for seven saponinsAnalytes Calibration curve ar2Test range(μg)LOD(μg)LOQ(μg)1 y=6711.9x－377.6 0.9940 0.56–22.01 0.26 0.882 y=7812.6x－411.9 0.9922 0.54–21.63 0.26 0.843 y=6798.5x－299.0 0.9958 0.46–18.42 0.22 0.724 y=12805x－487.9 0.9961 0.38–15.66 0.10 0.345 y=4143.8x－88.62 0.9989 0.42–16.82 0.18 0.246 y=3946.8x－94.4 0.9977 0.40–16.02 0.16 0.207 y=4287.8x－95.2 0.9982 0.42–16.46 0.12 0.22a y: Peak area; x: concentration (mg/ml)Table 2 Reproducibility of the assayAnalyteIntra-day variability Inter-day variability Content (mg/g) Mean RSD (%) Content (mg/g) Mean RSD (%)1 46.1646.2846.2246.22 0.1346.2245.3647.4226.33 2.232 5.385.385.165.31 2.405.285.345.045.22 3.043 4.374.304.184.28 2.244.284.464.024.255.204 nd1)-- -- nd -- --5 1.761.801.821.79 1.701.801.681.841.77 4.706 1.281.241.221.252.451.241.341.201.26 5.727 tr2)-- -- tr -- -- 1): not detected; 2): trace. RSD (%) = (SD/Mean) ×100%Table 3 Recovery of the seven analytesAnalyteOriginal(mg) Spiked(mg)Found(mg)Recovery(%)Mean(%)RSD(%)1 23.0823.1423.1119.7122.8628.1042.7346.1351.0199.7100.699.399.8 0.722.692.672.582.082.913.164.735.515.7698.197.6100.698.8 1.632.172.152.091.732.182.623.884.404.6598.8103.297.799.9 2.94nd1)1.011.050.980.981.101.0297.0104.8104.1102.0 4.250.880.900.910.700.871.081.561.752.0197.197.7101.898.9 2.660.640.620.610.450.610.751.081.211.3397.796.796.096.8 0.97tr2)1.021.101.081.031.111.07100.9102.799.1100.9 1.81): not detected; 2): trace.a Recovery (%) = (Amount found –Original amount)/ Amount spiked ×100%, RSD (%) = (SD/Mean) ×100%Table 4 Contents of seven saponins in Lonicera spp.Content (mg/g)1 2 3 4 5 6 7 L. confusa45.65±0.32 5.13±0.08 4.45±0.11tr1) 2.04±0.04tr 1.81±0.03 L. japonica nd2)nd 3.44±0.09nd nd nd nd L. macranthoides46.22±0.06 5.31±0.13 4.28±0.10 tr 1.79±0.03 1.25±0.03 tr L. hypoglauca11.17±0.07 nq3)53.78±1.18nd 1.72±0.02 2.23±0.06 2.52±0.04 L. similes41.22±0.25 4.57±0.07 3.79±0.09nd 1.75±0.02tr nd 1): trace; 2): not detected.. 3) not quantified owing to the suspicious purity of the peak.。

阿洛西林说明书你知道阿洛西林吗?你清楚知道阿洛西林吗?下面是店铺为你整理的阿洛西林说明书的相关内容，希望对你有用!阿洛西林物化信息中文名称:阿洛西林中文别名:咪氨苄西林;英文名称:Azlocillin英文别名:3,3-Dimethyl-6-oxo-7-[2-(2-oxoimidazolidin-1-yl)carbonylamino-2-phenyl-acetyl]amino-2-thia-5-azabicyclo[3.2.0]heptane-4-carboxylic acid;[1]CAS:37091-66-0EINECS:253-348-2分子式:C20H23N5O6S分子量:461.4915物化性质相对密度:1.55g/cm3阿洛西林作用用途本品抗菌作用与哌拉西林相似，抗绿脓杆菌活性较强，与哌拉西林相似，对耐庆大霉素和羧苄西林的绿脓杆菌也有较好作用，抗菌谱包括大肠杆菌、变形杆菌、克雷白肺炎杆菌、绿脓杆菌、肠杆菌、嗜血杆菌等。

临床应用于治疗绿脓杆菌等革兰阴性菌所引起的各种感染，如尿路感染及呼吸道感染等。

阿洛西林剂量用法一般2g/次，1次/8小时，肌注、静注或静滴。

重症5g/次，1次/8小时。

小于7日的新生儿每次100mg/kg，2次/日;婴儿每次100mg/kg，3次/日;儿童每次75mg/kg，3次/日。

阿洛西林药理阿洛西林对大多革兰阴性菌(包括绿脓杆菌)、革兰阳性球菌和厌氧菌皆有抗菌作用。

对绿脓杆菌的抗菌活性较强，为美洛西林的 2～4倍，与哌拉西林相似; 对耐庆大霉素和羧苄西林的绿脓杆菌也有较好的作用。

本品对链球菌、肠球菌属的抗菌活性与氨苄西林相似，对部分脆弱类杆菌也有较好作用。

本品对细菌产生的β内酰胺酶不稳定。

阿洛西林药动学快速静脉注射lg阿洛西林后5min的血药峰浓度为92.9mg/L，于30min内静脉滴注阿洛西林5g，滴注结束时的血药浓度为409mg/L，血清半减期约为 1h。

阿洛西林在支气管分泌物及组织间液和伤口渗出物中浓度高;脑膜有炎症时，脑脊液中浓度可达同期血药浓度的10%～30%。

HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationFLUOXETINE HClC17H18F3NO•HClM.W. = 345.79CAS — 59333-67-4STABILITY INDICATINGA S S A Y V A L I D A T I O NMethod is suitable for:ýIn-process controlþProduct ReleaseþStability indicating analysis (Suitability - US/EU Product) CAUTIONFLUOXETINE HYDROCHLORIDE IS A HAZARDOUS CHEMICAL AND SHOULD BE HANDLED ONLY UNDER CONDITIONS SUITABLE FOR HAZARDOUS WORK.IT IS HIGHLY PRESSURE SENSITIVE AND ADEQUATE PRECAUTIONS SHOULD BE TAKEN TO AVOID ANY MECHANICAL FORCE (SUCH AS GRINDING, CRUSHING, ETC.) ON THE POWDER.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationTABLE OF CONTENTS INTRODUCTION........................................................................................................................ PRECISION............................................................................................................................... System Repeatability ................................................................................................................ Method Repeatability................................................................................................................. Intermediate Precision .............................................................................................................. LINEARITY................................................................................................................................ RANGE...................................................................................................................................... ACCURACY............................................................................................................................... Accuracy of Standard Injections................................................................................................ Accuracy of the Drug Product.................................................................................................... VALIDATION OF FLUOXETINE HCl AT LOW CONCENTRATION........................................... Linearity at Low Concentrations................................................................................................. Accuracy of Fluoxetine HCl at Low Concentration..................................................................... System Repeatability................................................................................................................. Quantitation Limit....................................................................................................................... Detection Limit........................................................................................................................... VALIDATION FOR META-FLUOXETINE HCl (POSSIBLE IMPURITIES).................................. Meta-Fluoxetine HCl linearity at 0.05% - 1.0%........................................................................... Detection Limit for Fluoxetine HCl.............................................................................................. Quantitation Limit for Meta Fluoxetine HCl................................................................................ Accuracy for Meta-Fluoxetine HCl ............................................................................................ Method Repeatability for Meta-Fluoxetine HCl........................................................................... Intermediate Precision for Meta-Fluoxetine HCl......................................................................... SPECIFICITY - STABILITY INDICATING EVALUATION OF THE METHOD............................. FORCED DEGRADATION OF FINISHED PRODUCT AND STANDARD..................................1. Unstressed analysis...............................................................................................................2. Acid Hydrolysis stressed analysis..........................................................................................3. Base hydrolysis stressed analysis.........................................................................................4. Oxidation stressed analysis...................................................................................................5. Sunlight stressed analysis.....................................................................................................6. Heat of solution stressed analysis.........................................................................................7. Heat of powder stressed analysis.......................................................................................... System Suitability stressed analysis.......................................................................................... Placebo...................................................................................................................................... STABILITY OF STANDARD AND SAMPLE SOLUTIONS......................................................... Standard Solution...................................................................................................................... Sample Solutions....................................................................................................................... ROBUSTNESS.......................................................................................................................... Extraction................................................................................................................................... Factorial Design......................................................................................................................... CONCLUSION...........................................................................................................................ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationBACKGROUNDTherapeutically, Fluoxetine hydrochloride is a classified as a selective serotonin-reuptake inhibitor. Effectively used for the treatment of various depressions. Fluoxetine hydrochloride has been shown to have comparable efficacy to tricyclic antidepressants but with fewer anticholinergic side effects. The patent expiry becomes effective in 2001 (US). INTRODUCTIONFluoxetine capsules were prepared in two dosage strengths: 10mg and 20mg dosage strengths with the same capsule weight. The formulas are essentially similar and geometrically equivalent with the same ingredients and proportions. Minor changes in non-active proportions account for the change in active ingredient amounts from the 10 and 20 mg strength.The following validation, for the method SI-IAG-206-02 , includes assay and determination of Meta-Fluoxetine by HPLC, is based on the analytical method validation SI-IAG-209-06. Currently the method is the in-house method performed for Stability Studies. The Validation was performed on the 20mg dosage samples, IAG-21-001 and IAG-21-002.In the forced degradation studies, the two placebo samples were also used. PRECISIONSYSTEM REPEATABILITYFive replicate injections of the standard solution at the concentration of 0.4242mg/mL as described in method SI-IAG-206-02 were made and the relative standard deviation (RSD) of the peak areas was calculated.SAMPLE PEAK AREA#15390#25406#35405#45405#55406Average5402.7SD 6.1% RSD0.1ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::PRECISION - Method RepeatabilityThe full HPLC method as described in SI-IAG-206-02 was carried-out on the finished product IAG-21-001 for the 20mg dosage form. The method repeated six times and the relative standard deviation (RSD) was calculated.SAMPLENumber%ASSAYof labeled amountI 96.9II 97.8III 98.2IV 97.4V 97.7VI 98.5(%) Average97.7SD 0.6(%) RSD0.6PRECISION - Intermediate PrecisionThe full method as described in SI-IAG-206-02 was carried-out on the finished product IAG-21-001 for the 20mg dosage form. The method was repeated six times by a second analyst on a different day using a different HPLC instrument. The average assay and the relative standard deviation (RSD) were calculated.SAMPLENumber% ASSAYof labeled amountI 98.3II 96.3III 94.6IV 96.3V 97.8VI 93.3Average (%)96.1SD 2.0RSD (%)2.1The difference between the average results of method repeatability and the intermediate precision is 1.7%.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationLINEARITYStandard solutions were prepared at 50% to 200% of the nominal concentration required by the assay procedure. Linear regression analysis demonstrated acceptability of the method for quantitative analysis over the concentration range required. Y-Intercept was found to be insignificant.RANGEDifferent concentrations of the sample (IAG-21-001) for the 20mg dosage form were prepared, covering between 50% - 200% of the nominal weight of the sample.Conc. (%)Conc. (mg/mL)Peak Area% Assayof labeled amount500.20116235096.7700.27935334099.21000.39734463296.61500.64480757797.52000.79448939497.9(%) Average97.6SD 1.0(%) RSD 1.0ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::RANGE (cont.)The results demonstrate linearity as well over the specified range.Correlation coefficient (RSQ)0.99981 Slope11808.3Y -Interceptresponse at 100%* 100 (%) 0.3%ACCURACYACCURACY OF STANDARD INJECTIONSFive (5) replicate injections of the working standard solution at concentration of 0.4242mg/mL, as described in method SI-IAG-206-02 were made.INJECTIONNO.PEAK AREA%ACCURACYI 539299.7II 540599.9III 540499.9IV 5406100.0V 5407100.0Average 5402.899.9%SD 6.10.1RSD, (%)0.10.1The percent deviation from the true value wasdetermined from the linear regression lineHPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::ACCURACY OF THE DRUG PRODUCTAdmixtures of non-actives (placebo, batch IAG-21-001 ) with Fluoxetine HCl were prepared at the same proportion as in a capsule (70%-180% of the nominal concentration).Three preparations were made for each concentration and the recovery was calculated.Conc.(%)Placebo Wt.(mg)Fluoxetine HCl Wt.(mg)Peak Area%Accuracy Average (%)70%7079.477.843465102.27079.687.873427100.77079.618.013465100.0101.0100%10079.6211.25476397.910080.8011.42491799.610079.6011.42485498.398.6130%13079.7214.90640599.413080.3114.75632899.213081.3314.766402100.399.618079.9920.10863699.318079.3820.45879499.418080.0820.32874899.599.4Placebo, Batch Lot IAG-21-001HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::VALIDATION OF FLUOXETINE HClAT LOW CONCENTRATIONLINEARITY AT LOW CONCENTRATIONSStandard solution of Fluoxetine were prepared at approximately 0.02%-1.0% of the working concentration required by the method SI-IAG-206-02. Linear regression analysis demonstrated acceptability of the method for quantitative analysis over this range.ACCURACY OF FLUOXETINE HCl AT LOW CONCENTRATIONThe peak areas of the standard solution at the working concentration were measured and the percent deviation from the true value, as determined from the linear regression was calculated.SAMPLECONC.µg/100mLAREA FOUND%ACCURACYI 470.56258499.7II 470.56359098.1III 470.561585101.3IV 470.561940100.7V 470.56252599.8VI 470.56271599.5(%) AverageSlope = 132.7395299.9SD Y-Intercept = -65.872371.1(%) RSD1.1HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSystem RepeatabilitySix replicate injections of standard solution at 0.02% and 0.05% of working concentration as described in method SI-IAG-206-02 were made and the relative standard deviation was calculated.SAMPLE FLUOXETINE HCl AREA0.02%0.05%I10173623II11503731III10103475IV10623390V10393315VI10953235Average10623462RSD, (%) 5.0 5.4Quantitation Limit - QLThe quantitation limit ( QL) was established by determining the minimum level at which the analyte was quantified. The quantitation limit for Fluoxetine HCl is 0.02% of the working standard concentration with resulting RSD (for six injections) of 5.0%. Detection Limit - DLThe detection limit (DL) was established by determining the minimum level at which the analyte was reliably detected. The detection limit of Fluoxetine HCl is about 0.01% of the working standard concentration.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::VALIDATION FOR META-FLUOXETINE HCl(EVALUATING POSSIBLE IMPURITIES)Meta-Fluoxetine HCl linearity at 0.05% - 1.0%Relative Response Factor (F)Relative response factor for Meta-Fluoxetine HCl was determined as slope of Fluoxetine HCl divided by the slope of Meta-Fluoxetine HCl from the linearity graphs (analysed at the same time).F =132.7395274.859534= 1.8Detection Limit (DL) for Fluoxetine HClThe detection limit (DL) was established by determining the minimum level at which the analyte was reliably detected.Detection limit for Meta Fluoxetine HCl is about 0.02%.Quantitation Limit (QL) for Meta-Fluoxetine HClThe QL is determined by the analysis of samples with known concentration of Meta-Fluoxetine HCl and by establishing the minimum level at which the Meta-Fluoxetine HCl can be quantified with acceptable accuracy and precision.Six individual preparations of standard and placebo spiked with Meta-Fluoxetine HCl solution to give solution with 0.05% of Meta Fluoxetine HCl, were injected into the HPLC and the recovery was calculated.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::META-FLUOXETINE HCl[RECOVERY IN SPIKED SAMPLES].Approx.Conc.(%)Known Conc.(µg/100ml)Area in SpikedSampleFound Conc.(µg/100mL)Recovery (%)0.0521.783326125.735118.10.0521.783326825.821118.50.0521.783292021.55799.00.0521.783324125.490117.00.0521.783287220.96996.30.0521.783328526.030119.5(%) AVERAGE111.4SD The recovery result of 6 samples is between 80%-120%.10.7(%) RSDQL for Meta Fluoxetine HCl is 0.05%.9.6Accuracy for Meta Fluoxetine HClDetermination of Accuracy for Meta-Fluoxetine HCl impurity was assessed using triplicate samples (of the drug product) spiked with known quantities of Meta Fluoxetine HCl impurity at three concentrations levels (namely 80%, 100% and 120% of the specified limit - 0.05%).The results are within specifications:For 0.4% and 0.5% recovery of 85% -115%For 0.6% recovery of 90%-110%HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::META-FLUOXETINE HCl[RECOVERY IN SPIKED SAMPLES]Approx.Conc.(%)Known Conc.(µg/100mL)Area in spikedSample Found Conc.(µg/100mL)Recovery (%)[0.4%]0.4174.2614283182.66104.820.4174.2614606187.11107.370.4174.2614351183.59105.36[0.5%]0.5217.8317344224.85103.220.5217.8316713216.1599.230.5217.8317341224.81103.20[0.6%]0.6261.3918367238.9591.420.6261.3920606269.81103.220.6261.3920237264.73101.28RECOVERY DATA DETERMINED IN SPIKED SAMPLESHPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::REPEATABILITYMethod Repeatability - Meta Fluoxetine HClThe full method (as described in SI-IAG-206-02) was carried out on the finished drug product representing lot number IAG-21-001-(1). The HPLC method repeated serially, six times and the relative standard deviation (RSD) was calculated.IAG-21-001 20mg CAPSULES - FLUOXETINESample% Meta Fluoxetine % Meta-Fluoxetine 1 in Spiked Solution10.0260.09520.0270.08630.0320.07740.0300.07450.0240.09060.0280.063AVERAGE (%)0.0280.081SD 0.0030.012RSD, (%)10.314.51NOTE :All results are less than QL (0.05%) therefore spiked samples with 0.05% Meta Fluoxetine HCl were injected.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::Intermediate Precision - Meta-Fluoxetine HClThe full method as described in SI-IAG-206-02 was applied on the finished product IAG-21-001-(1) .It was repeated six times, with a different analyst on a different day using a different HPLC instrument.The difference between the average results obtained by the method repeatability and the intermediate precision was less than 30.0%, (11.4% for Meta-Fluoxetine HCl as is and 28.5% for spiked solution).IAG-21-001 20mg - CAPSULES FLUOXETINESample N o:Percentage Meta-fluoxetine% Meta-fluoxetine 1 in spiked solution10.0260.06920.0270.05730.0120.06140.0210.05850.0360.05560.0270.079(%) AVERAGE0.0250.063SD 0.0080.009(%) RSD31.514.51NOTE:All results obtained were well below the QL (0.05%) thus spiked samples slightly greater than 0.05% Meta-Fluoxetine HCl were injected. The RSD at the QL of the spiked solution was 14.5%HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSPECIFICITY - STABILITY INDICATING EVALUATIONDemonstration of the Stability Indicating parameters of the HPLC assay method [SI-IAG-206-02] for Fluoxetine 10 & 20mg capsules, a suitable photo-diode array detector was incorporated utilizing a commercial chromatography software managing system2, and applied to analyze a range of stressed samples of the finished drug product.GLOSSARY of PEAK PURITY RESULT NOTATION (as reported2):Purity Angle-is a measure of spectral non-homogeneity across a peak, i.e. the weighed average of all spectral contrast angles calculated by comparing all spectra in the integrated peak against the peak apex spectrum.Purity Threshold-is the sum of noise angle3 and solvent angle4. It is the limit of detection of shape differences between two spectra.Match Angle-is a comparison of the spectrum at the peak apex against a library spectrum.Match Threshold-is the sum of the match noise angle3 and match solvent angle4.3Noise Angle-is a measure of spectral non-homogeneity caused by system noise.4Solvent Angle-is a measure of spectral non-homogeneity caused by solvent composition.OVERVIEWT he assay of the main peak in each stressed solution is calculated according to the assay method SI-IAG-206-02, against the Standard Solution, injected on the same day.I f the Purity Angle is smaller than the Purity Threshold and the Match Angle is smaller than the Match Threshold, no significant differences between spectra can be detected. As a result no spectroscopic evidence for co-elution is evident and the peak is considered to be pure.T he stressed condition study indicated that the Fluoxetine peak is free from any appreciable degradation interference under the stressed conditions tested. Observed degradation products peaks were well separated from the main peak.1® PDA-996 Waters™ ; 2[Millennium 2010]ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationFORCED DEGRADATION OF FINISHED PRODUCT & STANDARD 1.UNSTRESSED SAMPLE1.1.Sample IAG-21-001 (2) (20mg/capsule) was prepared as stated in SI-IAG-206-02 and injected into the HPLC system. The calculated assay is 98.5%.SAMPLE - UNSTRESSEDFluoxetine:Purity Angle:0.075Match Angle:0.407Purity Threshold:0.142Match Threshold:0.4251.2.Standard solution was prepared as stated in method SI-IAG-206-02 and injected into the HPLC system. The calculated assay is 100.0%.Fluoxetine:Purity Angle:0.078Match Angle:0.379Purity Threshold:0.146Match Threshold:0.4272.ACID HYDROLYSIS2.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as in method SI-IAG-206-02 : An amount equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent was added and the solution sonicated for 10 minutes. 1mL of conc. HCl was added to this solution The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with NaOH 10N, made up to volume with Diluent and injected into the HPLC system after filtration.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 98.8%.SAMPLE- ACID HYDROLYSISFluoxetine peak:Purity Angle:0.055Match Angle:0.143Purity Threshold:0.096Match Threshold:0.3712.2.Standard solution was prepared as in method SI-IAG-206-02 : about 22mg Fluoxetine HCl were weighed into a 50mL volumetric flask. 20mL Diluent were added. 2mL of conc. HCl were added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with NaOH 10N, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 97.2%.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSTANDARD - ACID HYDROLYSISFluoxetine peak:Purity Angle:0.060Match Angle:0.060Purity Threshold:0.099Match Threshold:0.3713.BASE HYDROLYSIS3.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as per method SI-IAG-206-02 : An amount equivalent to 20mg Fluoxetine was weight into a 50mL volumetric flask. 20mL Diluent was added and the solution sonicated for 10 minutes. 1mL of 5N NaOH was added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with 5N HCl, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 99.3%.SAMPLE - BASE HYDROLYSISFluoxetine peak:Purity Angle:0.063Match Angle:0.065Purity Threshold:0.099Match Threshold:0.3623.2.Standard stock solution was prepared as per method SI-IAG-206-02 : About 22mg Fluoxetine HCl was weighed into a 50mL volumetric flask. 20mL Diluent was added. 2mL of 5N NaOH was added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH=5.5 with 5N HCl, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease - 99.5%.STANDARD - BASE HYDROLYSISFluoxetine peak:Purity Angle:0.081Match Angle:0.096Purity Threshold:0.103Match Threshold:0.3634.OXIDATION4.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as per method SI-IAG-206-02. An equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent added and the solution sonicated for 10 minutes.1.0mL of 30% H2O2 was added to the solution and allowed to stand for 5 hours, then made up to volume with Diluent, filtered and injected into HPLC system.Fluoxetine peak intensity decreased to 95.2%.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSAMPLE - OXIDATIONFluoxetine peak:Purity Angle:0.090Match Angle:0.400Purity Threshold:0.154Match Threshold:0.4294.2.Standard solution was prepared as in method SI-IAG-206-02 : about 22mg Fluoxetine HCl were weighed into a 50mL volumetric flask and 25mL Diluent were added. 2mL of 30% H2O2 were added to this solution which was standing for 5 hours, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity decreased to 95.8%.STANDARD - OXIDATIONFluoxetine peak:Purity Angle:0.083Match Angle:0.416Purity Threshold:0.153Match Threshold:0.4295.SUNLIGHT5.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as in method SI-IAG-206-02 . The solution was exposed to 500w/hr. cell sunlight for 1hour. The BST was set to 35°C and the ACT was 45°C. The vials were placed in a horizontal position (4mm vials, National + Septum were used). A Dark control solution was tested. A 2%w/v quinine solution was used as the reference absorbance solution.Fluoxetine peak decreased to 91.2% and the dark control solution showed assay of 97.0%. The difference in the absorbance in the quinine solution is 0.4227AU.Additional peak was observed at RRT of 1.5 (2.7%).The total percent of Fluoxetine peak with the degradation peak is about 93.9%.SAMPLE - SUNLIGHTFluoxetine peak:Purity Angle:0.093Match Angle:0.583Purity Threshold:0.148Match Threshold:0.825 ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSUNLIGHT (Cont.)5.2.Working standard solution was prepared as in method SI-IAG-206-02 . The solution was exposed to 500w/hr. cell sunlight for 1.5 hour. The BST was set to 35°C and the ACT was 42°C. The vials were placed in a horizontal position (4mm vials, National + Septum were used). A Dark control solution was tested. A 2%w/v quinine solution was used as the reference absorbance solution.Fluoxetine peak was decreased to 95.2% and the dark control solution showed assay of 99.5%.The difference in the absorbance in the quinine solution is 0.4227AU.Additional peak were observed at RRT of 1.5 (2.3).The total percent of Fluoxetine peak with the degradation peak is about 97.5%. STANDARD - SUNLIGHTFluoxetine peak:Purity Angle:0.067Match Angle:0.389Purity Threshold:0.134Match Threshold:0.8196.HEAT OF SOLUTION6.1.Sample solution of IAG-21-001-(2) (20 mg/capsule) was prepared as in method SI-IAG-206-02 . Equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent was added and the solution was sonicated for 10 minutes and made up to volume with Diluent. 4mL solution was transferred into a suitable crucible, heated at 105°C in an oven for 2 hours. The sample was cooled to ambient temperature, filtered and injected into the HPLC system.Fluoxetine peak was decreased to 93.3%.SAMPLE - HEAT OF SOLUTION [105o C]Fluoxetine peak:Purity Angle:0.062Match Angle:0.460Purity Threshold:0.131Match Threshold:0.8186.2.Standard Working Solution (WS) was prepared under method SI-IAG-206-02 . 4mL of the working solution was transferred into a suitable crucible, placed in an oven at 105°C for 2 hours, cooled to ambient temperature and injected into the HPLC system.Fluoxetine peak intensity did not decrease - 100.5%.ED. N0: 04Effective Date:APPROVED::。

己烯雌酚（DES）/乙烯雌酚检测
己烯雌酚（Diethylstilbestrol, DES），又称为乙烯雌酚、丙酸已烯雌酚，是人工合成的非甾体雌激素物质，主要用于雌激素低下症及激素平衡失调引起的功能性出血、闭经，还可用于死胎引产前，以提高子宫肌层对催产素的敏感性。

迪信泰检测平台采用高效液相色谱(HPLC)法，可高效、精准的检测己烯雌酚的含量变化。

对于常见雌性激素或以上雌性激素的同类物质，可配合标准物质进行检测，对于稀有的雌性激素，如提供标准样品，迪信泰检测平台可提供定制检测。

此外，我们还提供其他激素检测服务、动物激素检测服务，以满足您的不同需求。

样品制备
1）取100 mL样品；
2）盐酸调解pH值为2-3；
3）样品通过10 mL甲醇和10 mL去离子水活化的SPE柱进行萃取；
4）真空泵抽去SPE柱残留的水分；
5）10 mL二氯甲烷-甲醇(V/V=80/20)洗脱；
6）氮气吹干洗脱液；
7）甲醇溶解定容至1 mL；
8）用HPLC分析。

HPLC测定己烯雌酚样本要求：
1. 请确保样本量大于0.2g或者0.2mL。

周期：2~3周
项目结束后迪信泰检测平台将会提供详细中英文双语技术报告，报告包括：
1. 实验步骤（中英文）
2. 相关质谱参数（中英文）
3. 质谱图片
4. 原始数据
5. 己烯雌酚含量信息。

CODEX GENERAL STANDARD FOR CONTAMINANTS AND TOXINSIN FOOD AND FEEDCODEX STAN 193-1995 1. PREAMBLE1.1 S COPEThis Standard contains the main principles which are recommended by the Codex Alimentarius in dealing with contaminants and toxins in food and feed, and lists the maximum levels and associated sampling plans of contaminants and natural toxicants in food and feed which are recommended by the CAC to be applied to commodities moving in international trade.This standard includes only maximum levels of contaminants and natural toxicants in feed in cases where the contaminant in feed can be transferred to food of animal origin and can be relevant for public health.1.2 D EFINITION OF T ERMS1.2.1 GeneralThe definitions for the purpose of the Codex Alimentarius, as mentioned in the Procedural Manual, are applicable to the General Standard for Contaminants and Toxins in Food and Feed (GSCTFF) and only the most important ones are repeated here. Some new definitions are introduced, where this seems warranted to obtain optimal clarity. When reference is made to foods, this also applies to animal feed, in those cases where this is appropriate.1.2.2 ContaminantCodex Alimentarius defines a contaminant as follows:"Any substance not intentionally added to food, which is present in such food as a result of the production (including operations carried out in crop husbandry, animal husbandry and veterinary medicine), manufacture, processing, preparation, treatment, packing, packaging, transport or holding of such food or as a result of environmental contamination. The term does not include insect fragments, rodent hairs and other extraneous matter".This standard applies to any substance that meets the terms of the Codex definition for a contaminant, including contaminants in feed for food-producing animals, except:foodonlyand feed quality significance (e.g. copper), but no public healthhaving1) Contaminantssignificance, in the food(s) given that the standards elaborated within the Codex Committee onContaminants in Foods (CCCF) has the objective to protect public health.2) Pesticide residues, as defined by the Codex definition that are within the terms of reference of the CodexCommittee on Pesticide Residues (CCPR).3) Residues of veterinary drugs, as defined by the Codex definition, that are within the terms of reference ofthe Codex Committee on Residues of Veterinary Drugs in Foods (CCRVDF).4) Microbial toxins, such as botulinum toxin and staphylococcus enterotoxin, and microorganisms that arewithin the terms of reference of the Codex Committee on Food Hygiene (CCFH).5) Residues of processing aids that are within the terms of reference of the Codex Committee on FoodAdditives (CCFA)1 .1.2.3 Natural toxins included in this standardThe Codex definition of a contaminant implicitly includes naturally occurring toxicants including toxic metabolites of certain microfungi that are not intentionally added to food and feed (mycotoxins).Toxins that are produced by algae and that may be accumulated in edible aquatic organisms such as shellfish (phycotoxins) are also included in this standard. Mycotoxins and phycotoxins are both subclasses of contaminants.1Processing aids are any substance or material, not including apparatus or utensils, and not consumed as a food ingredient by itself, intentionally used in the processing of raw materials, foods or its ingredients, to fulfil a certain technological purpose during treatment or processing and which may result in the non-intentional but unavoidable presence of residues or derivatives in the final product.Adopted 1995; Revised 1997, 2006, 2008, 2009; Amended 2009, 2010Endogenous natural toxicants, such as e.g. solanine in potatoes, that are implicit constituents of food and feed resulting from a genus, species or strain ordinarily producing hazardous levels of a toxic metabolite(s), i.e. phytotoxins are not generally considered within the scope of this standard. They are, however, within the terms of reference of the CCCF and will be dealt with on a case by case basis.1.2.4 Maximum level and related terms2The Codex maximum level(ML) for a contaminant in a food or feed commodity is the maximum concentration of that substance recommended by the Codex Alimentarius Commission (CAC) to be legally permitted in that commodity.1.3 P RINCIPLES R EGARDING C ONTAMINANTS IN F OOD AND FEED1.3.1 GeneralContamination of food and feed may pose a risk to human (and/or animal health). Moreover in some cases they may also have a negative impact on the quality of the food or feed. Food and feed can become contaminated by various causes and processes.Contaminant levels in food and feed shall be as low as reasonably achievable through best practice such as Good Agricultural Practice (GAP) and Good Manufacturing Practice (GMP) following an appropriate risk assessment. The following actions may serve to prevent or to reduce contamination of feed and food3:- preventing food and feed contamination at the source, e.g. by reducing environmental pollution.- applying appropriate technology control measure(s) in food and feed production, manufacture, processing, preparation, treatment, packing, packaging, transport or holding.- applying measures aimed at decontamination of contaminated feed or food and measures to prevent contaminated feed or food to be marketed for consumption.To ensure that adequate action is taken to reduce contamination of food and feed a Code of Practice shall be elaborated comprising source related measures and Good Manufacturing Practice as well as Good Agricultural Practice in relation to the specific contamination problem.The degree of contamination of food and feed and the effect of actions to reduce contamination shall be assessed by monitoring, survey programs and more specialized research programs, where necessary.When there are indications that health hazards may be involved with consumption of food that is contaminated, it is necessary that a risk assessment should be undertaken. When health concerns can be substantiated, a risk management measure must be applied, based on a thorough evaluation of the situation and consideration of a range of risk management options. Depending on the assessment of the problems and the possible solutions, it may be necessary to establish MLs or other measures to control the contamination of food and feed. In special cases, specific advice on dietary recommendations may also have to be considered to complement other regulatory measures, when the measures are not sufficiently adequate to protect public health and safety.National measures regarding food and feed contamination should avoid the creation of unnecessary barriers to international trade in food and feed commodities. The purpose of the GSCTFF is to provide guidance about possible approaches to eliminate or reduce the contamination problem and to promote international harmonization through recommendations which in turn may prevent trade barriers and disputes.For all contaminants, which may be present in more than one feed or food item, a broad approach shall be applied, taking into account all relevant information that is available, for the assessing of risks and for developing recommendations and control measures, including the setting of maximum levels.1.3.2 Principles for establishing maximum levels in food and feedMLs shall only be set for food in which the contaminant may be found in amounts that are significant for the total exposure of the consumer, taking into consideration the Policy of the Codex Committee on Contaminants in Foods for Exposure Assessment of Contaminants and Toxins in Foods or Food Groups (Section III of the Procedural Manual)The maximum levels shall be set in such a way that the consumer is adequately protected. At the same time the other legitimate factors need to be considered. . This will be performed in accordance with the "Working principles for Risk Analysis for Food safety for Application by Governments".The principles of Good Manufacturing Practice and Good Agricultural Practice as defined by Codex shall be used. Maximum levels shall be based on sound scientific principles leading to levels which are acceptable worldwide, so that there is no unjustified barrier to international trade. MLs shall be clearly defined with respect to status and intended use. 2For the contaminants methylmercury, radionuclides, acrylonitrile and vinylchloride monomer a Codex guideline level (GL) has been established.A Codex guideline level(GL) is the maximum level of a substance in a food or feed commodity which is recommended by the CAC to beacceptable for commodities moving in international trade. When the GL is exceeded, governments should decide whether and under what circumstances the food should be distributed within their territory or jurisdiction.Because the CAC has decided that the preferred format of a Codex standard in food or feed is a maximum level, the present existing or proposed guideline levels shall be reviewed for their possible conversion to a maximum level after a risk assessment performed by JECFA, if appropriate.3In addition, reference is made to the Code of Practice for source Directed measures to reduce contamination of food with chemicals (CAC/RCP 49-2001) and the Code of Practice on Good Animal Feeding (CAC/RCP 54-2004)1.3.3 Specific criteriaThe following criteria should (not preventing the use of other relevant criteria) be considered when developing MLs and/or other measures in connection with the Codex General Standard for Contaminants and Toxins in Food and Feed : (Further details about these criteria are given in Annex I).informationToxicological-identification of the toxic substance(s);-metabolism by humans and animals, as appropriate;-toxicokinetics and toxicodynamics including information on possible carry-over of the toxic substance from feed to edible animal tissue/products;-information about acute and long term toxicity and other relevant toxicity data; and-integrated toxicological expert advice regarding the acceptability and safety of intake levels of contaminants, including information on any population groups which are specially vulnerable.dataAnalytical-validated qualitative and quantitative data on representative samples; and-appropriate sampling procedures.Intakedata-presence in food of dietary significance for the contaminant;-presence in food that are widely consumed;-presence in feed and feed components-food intake data for average and most exposed/high consumer groups;-results from total diet studies;-calculated contaminant intake data from food consumption models;-data on intake by susceptible groups; and-data on intake by food producing animals.Technological considerations-information about contamination processes, technological possibilities, production and manufacturing practices and economic aspects related to contaminant level management and control.Risk assessment and risk management considerations (cf."Working Principles for Risk Analysis for Food Safety for Application by Governments”)-risk management options and considerations;-consideration of possible maximum levels in food and feed based on the criteria mentioned above; and -consideration of alternative solutions.1.4 F ORMAT OF THE G ENERAL S TANDARD FOR C ONTAMINANTS IN F OOD AND FEEDThe General Standard for Contaminants and Toxins in Food and Feed contains one type of presentation for the Standards: Schedule I in which the standards are listed per contaminant in the various food and feed categories.In order to obtain maximum clarity, explanatory notes shall be added where appropriate. The format contains all elements necessary for full understanding of the meaning, background, application and scope of the standards and contains references to the relevant documents and reports on which the standard is based.A full description of the format is provided in Annex II.ANNEX I CRITERIA FOR THE ESTABLISHMENT OF MAXIMUM LEVELS IN FOOD AND FEEDIntroductionIn this Annex criteria are mentioned regarding information which is considered necessary for evaluating contaminant problems in food and feed and for the establishment of maximum levels. The criteria mentioned here are elaborated in more detail than in section 1.3.3. of the Preamble. Only those aspects that need further clarification are detailed; however, criteria or aspects that are not specifically detailed here should not be ruled out in the evaluation process. Toxicological informationIntegrated toxicological expert advice regarding a safe/tolerable intake level of a contaminant is essential when decisions about maximum levels in foods are considered. A recommendation from JECFA regarding the maximum allowable or tolerable intake, based on a full evaluation of an adequate toxicological data base, should be the main basis for decisions by Codex members. In urgent cases, it may be possible to rely on less developed evaluations from JECFA or on toxicological expert advice from other international or national bodies.When toxicological information is presented in relation to proposals for maximum levels for contaminants in food and feed, information about the following aspects is desirable:-identification of the toxic substance(s);-metabolism in humans and animals, as appropriate;-toxicokinetics and toxicodynamics including information on possible carry-over of the contaminant from feed to edible animal tissue/products;-information about acute and long term toxicity in animals and humans, including epidemiological data on humans and other relevant toxicity data;-conclusions and advice of toxicological expert(s) (groups), with references, including information on specially vulnerable population groups or animals.Analytical dataValidated qualitative and quantitative analytical data on representative samples should be supplied. Information on the analytical and sampling methods used and on the validation of the results is desirable. A statement on the representativeness of the samples for the contamination of the product in general (e.g. on a national basis) should be added. The portion of the commodity that was analyzed and to which the contaminant content is related should be clearly stated and preferably should be equivalent to the definition of the commodity for this purpose or to existing related contaminant regulation.Information on appropriate sampling procedures should be supplied. Special attention to this aspect is necessary in the case of contaminants that may not be homogeneously distributed in the product (e.g. mycotoxins in some commodities).Intake dataIt is desirable to have information about the contaminant concentrations in those foods or food groups that (together) are responsible for at least half and preferably 80% or more of the total dietary intake of the contaminant, both for consumers with average and high consumption patterns.Information about the presence of the contaminant in foods that are widely consumed(staple foods) is desirable in order to be able to make a satisfactory assessment of the contaminant intake and of risks associated with food trade.For the contaminants which can be present in food of animal origin as a consequence of the carry over from feed, information about the presence of the contaminant in the feed and feed components should be given. Furthermore the intake of contaminants by the different food producing animals and the resulting levels of the contaminant in the food of animal origin should be estimated.Food consumption data for average, most exposed (high consumers) and susceptible consumer groups are desirable for evaluations of (potential) intake of contaminants. This problem, however, has to be addressed differently on a national and on an international scale. It is therefore important to have information about both average and high consumption patterns regarding a wide variety of foodstuffs, so that for every contaminant the most exposed consumer groups may be identified for every contaminant. Detailed information about high consumption patterns is desirable, both regarding group identification criteria (e.g. age or sex differences, vegetarian or regional dietary customs, etc.) and statistical aspects.Dietary intake of contaminants: Reference is made to the Guidelines for the study of dietary intake of chemical contaminants (WHO, 1985 - http://whqlibdoc.who.int/offset/WHO_OFFSET_87.pdf). It is important to supply all relevant details, such as the type of study (duplicate diet, total diet or market basket study, selective study), and statistical details. Calculated contaminant intake data from food consumption models may also be useful. When results about food groups and about effects of preparation and cooking etc. are available, these should also be supplied.Technological considerationsInformation about the source of the contaminant and the way in which the food and feed is contaminated, possibly including information, if available, about contamination being present in parts only of the product, is essential for assessing the possibilities to control the contamination process and to be able to guarantee a desired product safety and quality. Where possible Source-related measures should be proposed. Good Manufacturing Practice (GMP)and/or Good Agricultural Practice (GAP)should also be adapted to control a contamination problem. When this is possible, maximum levels may be based on GMP or GAP considerations to establish at a level as low as reasonably achievable and necessary to protect the consumer. Considerations regarding the technological possibilities to control a contamination problem, e.g. by cleaning, should also be taken into account when a primary risk assessment model (theoretical maximum daily intake) shows possible intakes exceeding the toxicological reference value. In such a case the possibilities of lower contamination levels need further careful examination. Then a detailed study about all the aspects involved is necessary, so that decisions about maximum levels can be based on a thorough evaluation of both the public health arguments and the potential problem with complying with the proposed standard.Risk assessment and risk management considerationsRisk assessment and risk management are conducted in accordance with the Working Principles for Risk Analysis for Food Safety Application by Governments.Establishment of maximum levelsIn case it is decided that, on the basis of the outcome of the risk assessment, there is no need to establish a maximum level to protect public health as the level of hazard/risk does not pose a public health problem, this should be communicated in a transparent and accessible manner (e.g. by using the full format as provided for Schedule I and to mention in the box of Maximum level "not necessary").The establishment of maximum levels (MLs) of contaminants in food and feed involves several principles, some of which have already been mentioned in this Preamble. Briefly stated, the following criteria will help in maintaining a consistent policy in this matter:-MLs should be set only for those contaminants that present both a significant risk to public health and a known or expected problem in international trade.-MLs should be set only for food that is significant for the total exposure of the consumer to the contaminant. When identifying the significance of certain foods in the total exposure to the contaminant,the criteria contained in para 11 of the Policy of the Codex Committee on contaminants in Foods forExposure Assessment of Contaminants and Toxins in Foods or Food Groups (section III of the CodexAlimentarius Commission Procedural Manual) should be consulted.-MLs should be set as low as reasonably achievable and at levels necessary to protect the consumer.Providing it is acceptable from the toxicological point of view, MLs should be set at a level which is(slightly) higher than the normal range of variation in levels in food and feed that are produced withcurrent adequate technological methods, in order to avoid undue disruptions of food and feed productionand trade. Where possible, MLs should be based on GMP and/or GAP considerations in which the healthconcerns have been incorporated as a guiding principle to achieve contaminant levels as low asreasonably achievable and necessary to protect the consumer. Foods that are evidently contaminated bylocal situations or processing conditions that can be avoided by reasonably achievable means shall beexcluded in this evaluation, unless a higher ML can be shown to be acceptable from a public health pointof view and significant economic aspects are at stake.-Proposals for MLs in products should be based on data from various countries and sources, encompassing the main production areas/processes of those products, as far as they are engaged ininternational trade. When there is evidence that contamination patterns are sufficiently understood andwill be comparable on a global scale, more limited data may be enough.-MLs may be set for product groups when sufficient information is available about the contamination pattern for the whole group, or when there are other arguments that extrapolation is appropriate.-Numerical values for MLs should preferably be regular figures in a geometric scale (0.01, 0.02, 0.05, 0.1,0.2, 0.5, 1, 2, 5 etc.), unless this may pose problems in the acceptability of the MLs.-MLs should apply to representative samples per lot. If necessary, appropriate methods of sampling should be specified.-MLs should not be lower than a level which can be analyzed with methods of analysis that can readily be set up and applied in food and feed control laboratories, unless public health considerations necessitate alower ML which can only be controlled by means of a more elaborate and sensitive method of analysiswith an adequate lower detection limit. In all cases, a validated method of analysis should be availablewith which a ML can be controlled.-The contaminant as it should be analyzed and to which the ML applies should be clearly defined. The definition may include important metabolites when this is appropriate from an analytical or toxicologicalpoint of view. It may also be aimed at indicator substances which are chosen from a group of relatedcontaminants.-The product as it should be analyzed and to which the ML applies, should be clearly defined. In general, MLs are set on primary products. MLs should in general preferably be expressed as a level of thecontaminant related to the product as it is, on a fresh weight basis. In some cases, however, there may bevalid arguments to prefer expression on a dry weight basis (this might be in particular the case forcontaminants in feed) or on a fat weight basis (this might be in particular the case for fat solublecontaminants). Preferably the product should be defined as it moves in trade, with provisions wherenecessary for the removal of inedible parts that might interfere with the preparation and the analysis of thesample. The product definitions used by the CCPR and contained in the Classification of food and feedmay serve as guidance on this subject; other product definitions should only be used for specifiedreasons. For contaminant purposes, however, analysis and consequently MLs should preferably be onthe basis of the edible part of the product.For fat soluble contaminants which may accumulate in animal products, provisions should be appliedregarding the application of the ML to products with various fat content (comparable to the provisions forfat soluble pesticides).-Guidance is desirable regarding the possible application of MLs established for primary products to processed products and multi-ingredient products. When products are concentrated, dried or diluted, useof the concentration or dilution factor is generally appropriate in order to be able to obtain a primaryjudgement of the contaminant levels in these processed products. The maximum contaminantconcentration in a multi-ingredient food and feed can likewise be calculated from the composition of thefood and feed. Information regarding the behaviour of the contaminant during processing (e.g. washing,peeling, extraction, cooking, drying etc.) is however desirable to give more adequate guidance. Whencontaminant levels are consistently different in processed products related to the primary products fromwhich they are derived, and sufficient information is available about the contamination pattern, it may beappropriate to establish separate maximum levels for these processed products. This also applies whencontamination may occur during processing. In general however, MLs should preferably be set forprimary agricultural products and may be applied to processed, derived and multi-ingredient food andfeed by using appropriate conversion factors. When these factors are sufficiently known, they should bementioned in the suffix to the maximum level following the format of list of MLs as defined in Annex II.-MLs should preferably not be set higher than is acceptable in a primary (theoretical maximum intake and risk estimation) approach of their acceptability from a public health point of view. When this posesproblems in relation to other criteria for establishing MLs, further evaluations are necessary regarding thepossibilities to reduce the contaminant levels, e.g. by improving GAP and/or GMP conditions. When thisdoes not bring a satisfactory solution, further refined risk assessment and contaminant risk managementevaluations will have to be made in order to try to reach agreement about an acceptable ML.Procedure for risk assessment in relation to (proposed) MLsIt is more difficult to control food and feed contamination problems than in the case of food additives and pesticide residues. Proposed MLs will inevitably be influenced by this situation. In order to promote acceptance of Codex contaminant MLs, it is therefore important that assessments of the impact of those MLs on dietary exposure are done in a consistent and realistic way. The procedure involves assessment of the dietary intake in relation to the proposed or existing MLs and the toxicological reference value.In case a contaminant is carried over from feed to food of animal origin, the intake of a contaminant by the different food producing animal species and the resulting levels in the food of animal origin should be estimated.The best estimate of dietary intake involves the national dietary pattern and corrections for concentration changes during transport, storage, food preparation, for known levels in foods as consumed, etc. Caution is recommended when using other than average food consumption values, although it is considered appropriate to use relevant average food consumption data for identifiable subgroups of the population. Food consumption patterns with a higher intake of critical foods may be used in the intake calculations when this is part of an accepted national or international health protection and risk management policy. A harmonized approach using an appropriate intake estimation model that is as realistic as possible is recommended. (cf. the "Policy of the Codex Committee on contaminants in Foods for Exposure Assessment of Contaminants and Toxins in Foods or Food Groups" -section III of the Codex Alimentarius Commission Procedural Manual). Calculated data should where possible always be compared with measured intake data. Proposals for MLs should be accompanied by intake calculations and risk assessment conclusions regarding their impact on dietary intake and use. The intake calculations should follow the methodology described in the CCCF Policy for Exposure Assessment and, if appropriate, be accompanied by the generation of distribution curves for the concentration in specific foods/food groups (see paras 5-8 and 12-14 of the Policy of the Codex Committee on Contaminants in Foods for Exposure Assessment of Contaminants and Toxins in Foods in the Codex Alimentarius Commission Procedural Manual). Statements from Governments about the non-acceptance of (proposed) Codex MLs should refer to specified intake calculations and risk management conclusions which support this position.。