1、1UPLC超高效液相色谱药典应用文集3药典系国家对批准上市药品标准的统一集成和对其中共性问题的统一规范。是药品生产、供应、使用和监督管理部门必须共同遵循的法定依据，制定药典标准对加强药品质量监管、保证药品质量、保障用药安全有效、维护人民健康起着十分重要的作用。药物分析技术作为药典标准制定中不可或缺的组成部分，近些年来随着医药工业的发展得到了不断的完善和进步。同时，我们也看到产业的发展和药品监管新的形势需要更精准快捷的药物分析技术及理念，以实现更科学的药品质量控制与监督已经成为各国药典的共识。在这一全球共识下， 2015版中国药典在保留常规检测方法的基础上，进一步扩大了对药物分析新技术和新仪器方
2、法的应用，大大提升了药品质量控制水平。但是，由于一些新技术的特点和应用范围并不为广大同仁所知晓，同时业界对新技术的规范使用也需要一定的认知过程，使得这些新技术的广泛应用尚需时日。超高效液相色谱技术作为一种领先的分析技术，自 2004年面世以来，其高效、环保等优势就引起了制药行业的广泛关注， 2010年前后，各国药典就陆续引入了基于超高效液相色谱方法的药典各论。但由于各论的数量并不多，导致业界对这类药物分析新方法的稳定性和合规性存有一定的疑虑。如今，随着使用超高效液相色谱方法建立标准的新药大规模问世，美国在2016版美国药典( USP39)中增加了 57个基于超高效液相色谱方法的各论 ,各国药典
3、也将有新的各论陆续面世。由此也引发了大量中国制药企业对超高效液相色谱技术的关注，越来越多的中国企业期待采用超高效液相色谱方法建立药物标准。为了推动超高效液相色谱技术的应用，同时帮助中国制药企业顺应发展潮流，提升产业技术实力，中国药典 -沃特世联合开放实验室推出了本册超高效液相色谱药典应用文集。在体现联合开放实验室开放性和创新性原则的同时，能够通过本册应用文集，为今后国内外药典协同提供基础数据，也希望从法规的角度，解决有意愿使用超高效液相色谱技术的企业对于这项技术的疑惑。序国家药典委员会首席科学家目录中国药典 ( ChP)欧洲药典 ( EP)美国药典 ( USP)复方丹参滴丸护肝丸 / 胶囊 /
4、 颗粒奈韦拉平半水合物 / Nevirapine hemihydrate盐酸左卡巴斯汀 / Levocabastine Hydrochloride- Impurity C盐酸左卡巴斯汀 / Levocabastine Hydrochloride富马酸喹硫平 / quetiapine fumarate琥铂酸索非那新 / Solifenacin succinate硫酸羟氯喹 / Hydroxychloroquini sulfas 多粘菌素E甲磺酸钠 / Colistimethatum natricumUSP Drug Product Assay TestsOrganic Chemical Medi
5、cines盐酸多柔比星 / Doxorubicin Hydrochloride盐酸多柔比星注射液 /Doxorubicin Hydrochloride Injection注射用盐酸多柔比星 / Doxorubicin Hydrochloride for Injection环吡酮胺 / Ciclopirox Olamine环吡酮胺乳膏 / Ciclopirox Olamine Cream，Ciclopirox Cream卡马西平 / Carbamazepine卡马西平口服混悬剂 / Carbamazepine Oral Suspension卡马西平缓释片 / Carbamazepine Exte
6、nded-Release Tablets磷酸安他唑啉 / Antazoline Phosphate盐酸柔红霉素 / Daunorubicin Hydrochloride注射用盐酸柔红霉素 / Daunorubicin Hydrochloride for Injection双氯芬酸钾片 / Diclofenac Potassium Tablets双氯芬酸钠肠溶片 / Diclofenac Sodium Delayed-Release Tablets 双氯芬酸钠缓释片 /Diclofenac Sodium Extended-Release Tablets硫酸麻黄碱注射液 / Ephedrine S
7、ulfate Injection肾上腺素 / Epinephrine101214172123258927303234363840424446474951535557585960616263646567697071737577798081838586889092949698100102104105106哈西奈德 / Halcinonide米诺地尔溶液 / Minoxidil Topical Solution水杨酰胺/ Salicylamide马来酸氯苯那敏片 / Chlorpheniramine Maleate Tablets马来酸右氯苯那敏片/ Dexchlorpheniramine Male
8、ate Tablets维生素B12片/ Cyanocobalamin Tablets盐酸地尔硫卓缓释胶囊剂/ Diltiazem Hydrochloride Extended-Release Capsules 盐酸地尔硫卓片/ Diltiazem Hydrochloride Tablets盐酸多巴胺/ Dopamine Hydrochloride盐酸多巴胺注射液/ Dopamine Hydrochloride Injection盐酸羟嗪/ Hydroxyzine Hydrochloride盐酸羟嗪注射液/ Hydroxyzine Hydrochloride Injection盐酸羟嗪片/ Hy
9、droxyzine Hydrochloride Tablets盐酸羟嗪口服溶液 / Hydroxyzine Hydrochloride Oral Solution富马酸氯马斯汀/ Clemastine Fumarate富马酸氯马斯汀片/ Clemastine Fumarate Tablets盐酸氯米帕明/ Clomipramine Hydrochloride盐酸氯米帕明胶囊/ Clomipramine Hydrochloride Capsules盐酸氯米帕明复合口服混悬液/ Clomipramine Hydrochloride Compounded Oral Suspension, Veter
10、inary盐酸丙咪嗪片 / Imipramine Hydrochloride Tablets甲泼尼龙/ Methylprednisolone甲泼尼龙片/ Methylprednisolone Tablets 水杨酸局部泡沫剂/ Salicylic Acid Topical Foam噻吗洛尔片/ Timolol Maleate Tablets氨茶碱/ Aminophylline氨茶碱注射液/ Aminophylline Injection氨茶碱口服溶液 / Aminophylline Oral Solution氨茶碱片 / Aminophylline Tablets盐酸布比卡因/ Bupivac
11、aine Hydrochloride盐酸布比卡因注射液/ Bupivacaine Hydrochloride Injection盐酸布比卡因葡萄糖注射液/ Bupivacaine Hydrochloride in Dextrose Injection 双嘧达莫/ Dipyridamole双嘧达莫片/ Dipyridamole Tablets醋酸甲羟孕酮注射液 / Medroxyprogesterone Acetate Injectable Suspension 醋酸甲羟孕酮片 / Medroxyprogesterone Acetate Tablets茶碱/ Theophylline 茶碱口服液
12、 / Theophylline Oral Solution茶碱缓释片 / Theophylline Extended-Release Capsules茶碱葡萄糖注射液 / Theophylline in Dextrose Injection北五味子干浸膏 / Northern Schisandra Fruit Dry Extract 硫酸沙丁胺醇/ Albuterol Sulfate沙丁胺醇片/ Albuterol Tablets多西环素/多西霉素/ Doxycycline多西霉素胶囊/ Doxycycline Capsules多西霉素片/ Doxycycline Tablets口服多西环素
13、/ Doxycycline for Oral Suspension多西环素注射用粉末 / Doxycycline for Injection盐酸多西环素/ Doxycycline Hyclate盐酸多西环素胶囊/ Doxycycline Hyclate Capsules盐酸多西环素片/ Doxycycline Hyclate Tablets溴甲纳曲酮 / Methylnaltrexone Bromide硝酸硫康唑 / Sulconazole Nitrate盐酸苯海索片/ Trihexyphenidyl Hydrochloride Tablets伪麻黄碱硫酸盐 / Pseudoephedrine
14、 Sulfate磺胺多辛乙胺嘧啶片/ Sulfadoxine and Pyrimethamine Tablets三七干浸膏胶囊/ Tienchi Ginseng Root and Rhizome Dry Extract Capsules三七干浸膏片/ Tienchi Ginseng Root and Rhizome Dry Extract Tablets三七粉片/ Tienchi Ginseng Root and Rhizome Powder Tablets三七粉胶囊/ Tienchi Ginseng Root and Rhizome Powder Capsules氨氯地平与阿托伐他汀片/ A
15、mlodipine and Atorvastatin Tablets阿托伐他汀钙片/ Atorvastatin Calcium Tablets泼尼松 / Prednisone盐酸氯米帕明 / Clomipramine Hydrochloride108110112114116118119120121122125128130132134136138140142144146147148149150151152153154156157159161163164166168盐酸氯米帕明胶囊 / Clomipramine Hydrochloride Capsules奥美沙坦酯片 / Olmesartan M
16、edoxomil Tablets苯佐卡因、 氨苯丁酯 、盐酸丁卡因局部喷雾剂 / Benzocaine, Butamben, and Tetracaine Hydrochloride Topical Aerosol苯佐卡因、 氨苯丁酯 、盐酸丁卡因凝胶/ Benzocaine, Butamben, and Tetracaine Hydrochloride Gel 苯佐卡因、 氨苯丁酯 、盐酸丁卡因局部溶液/ Benzocaine, Butamben, and Tetracaine Hydrochloride Topical Solution美国植物药法典 ( HMC)灵芝/ Ganoderma
17、 lucidum Fruiting Body三七/ Panax notoginseng Root and Rhizome五味子 / Schisandra chinensis Fruit 牛樟芝 / Antrodia camphorata Fruiting Body1701731751778复方丹参滴丸 方法来源: 收载于中国药典一部， P1219处方: 丹参 三七 冰片指纹图谱:色谱柱: L1, 2.1 mm x 10 cm; 1.8 m (ACQUITY HSS T3)流动相: Solution A:0.02%磷酸的 80%乙腈溶液Solution B:0.02%磷酸溶液梯度条件:柱温 :
18、40 C 流速 (ml/min): 0.4 波长 (nm): 280对照指纹图谱:方法解析: 中药中成分复杂，采用 HPLC时，分析时间过长。现采用 UPLC进行指纹图谱分析，在保证分离度的前提下，大大提高了分析速度，节约检验成本。Time (min) Solution A (%) Solution B (%)0 9 911.6 22 781.8 26 748.0 39 618.4 9 9110 9 919护肝丸 / 胶囊 / 颗粒 方法来源: 收载于中国药典一部， P1219处方: 柴胡 626g 茵陈 626g 板蓝根 626g 五味子 336g 猪胆粉 40g 绿豆 256g含量测定:色
19、谱柱: L1, 2.1 mm 10 cm; 1.8 m (ACQUITY HSS T3)流动相: Solution A:乙腈Solution B:水梯度条件:柱温 : 40 C 流速 (ml/min): 0.4 波长 (nm): 250典型图谱:方法解析: 中药中成分复杂，采用 HPLC时，分析时间过长。现采用 UPLC进行指纹图谱分析，在保证分离度的前提下，大大提高了分析速度，节约检验成本。Time (min) Solution A (%) Solution B (%)0 45 553 45 5515 80 2010奈韦拉平半水合物Nevirapine hemihydrate方法来源: 收载
20、于 EP7.6/ Pharmeuropa 23.2结构式: 有关物质:色谱柱: L1, 2.1 mm x 5 cm; 1.8 m(ACQUITY UPLC HSS T3)流动相: Solution A:0.77 g乙酸铵加水 900 ml，加乙酸调至 pH=5.65.7，加水至 1000 mlSolution B:乙腈梯度条件:柱温 : 40 C 流速 (ml/min): 0.7 波长 (nm): 282色谱图:Time (min) Solution A (%) Solution B (%)0 - 1.35 90 101.35 - 3.85 9067 10333.85 - 6.70 6760
21、33406.70 - 7.65 60 4011Name 相对保留时间 可接受标准 (%)impurity B 0.9 0.2nevirapine 1.0 -impurity A 1.2 0.2impurity C 1.3 0.2单个未知杂质 - 0.10总杂质 - 0.6杂质结构杂质谱:impurity A11-ethyl-4-methyl-5,11-dihydro-6H-dipyrido3,2-b:2,3-e1,4diazepin-6-one,impurity C4-methyl-11-propyl-5,11-dihydro-6H-dipyrido3,2-b:2,3-e1,=4diazepi
22、n-6-one,impurity B4-methyl-5,11-dihydro-6H-dipyrido3,2-b:2,3-e1,4diazepin-6-oneimpurity D11,11-dicyclopropyl-4,4-dimethyl-5,5,11,11-tetrahydro-6H,6H-9,9-bidipyrido3,2-b:2,3-e1,4diazepine-6,6-dione12盐酸左卡巴斯汀 Levocabastine Hydrochloride -Impurity C方法来源: 收载于 Pharmeuropa 24.4, October 2012, P97结构式: Impur
23、ity C:色谱柱: L11, 2.1 mm x 10 cm; 1.7 m (ACQUITY UPLC BEH Phenyl)流动相: Solution A:17 g/L四丁基硫酸氢铵Solution B:乙腈梯度条件:柱温 : 35 C 流速 (ml/min): 0.3 波长 (nm): 214色谱图:Time (min) Solution A (%) Solution B (%)0 - 15 9080 102015 - 20 8050 205020 - 21 5090 501021 - 25 90 1013Name 相对保留时间 可接受标准 (%)impurity C 0.98 0.3le
24、vocabastine 1.0 -杂质结构杂质谱:impurity C(3S,4R)-1-cis-4-cyano-4-(3-fluorophenyl)cyclohexyl-3-methyl-4-phenylpiperidine-4-carboxylic acid,方法解析: 原方法采用毛细管电泳色谱( CE)进行分析，重现性与稳定性较差，操作比较复杂。现方法改用 UPLC进行分析，分析时间缩短，可操作性大大提高。14盐酸左卡巴斯汀 Levocabastine Hydrochloride 方法来源: 收载于 Pharmeuropa 24.4, October 2012, P98结构式: 有关物质
25、:色谱柱: L1, 2.1 mm x 15 cm; 1.8 m (ACQUITY UPLC HSS T3)流动相: Solution A:17 g/L四丁基硫酸氢铵Solution B:乙腈梯度条件:柱温 : 60 C 流速 (ml/min): 0.45 波长 (nm): 214色谱图:Time (min) Solution A (%) Solution B (%)0 - 3 9590 5103 - 55 9085 10155.5 - 10.5 8570 153010.5 - 14 7020 308014 - 15 20 8015Name 相对保留时间 可接受标准 (%)impurity A
26、0.85 0.2impurity J 0.86 -impurity B 0.90 0.15impurity E 0.94 0.4levocabastine 1.0 -impurity k 1.07 -单个未知杂质 - 0.10总杂质 - 0.6杂质结构杂质谱:impurity A(3S,4R)-1-(cis-4-cyano-4-phenylcyclohexyl)-3-methyl-4-phenylpiperidine-4-carboxylic acidimpurity C(3S,4R)-1-cis-4-cyano-4-(3-fluorophenyl)cyclohexyl-3-methyl-4-
27、phenylpiperidine-4- carboxylic acidimpurity B(3S,4R)-1-cis-4-cyano-4-(2-fluorophenyl)cyclohexyl-3-methyl-4-phenylpiperidine-4- carboxylic acidimpurity D1-cis-4-cyano-4-(4-fluorophenyl)cyclohexyl-4-phenylpiperidine-4-carboxylic acid16杂质结构impurity E(3S,4R)-1-trans-4-cyano-4-(4-fluorophenyl)cyclohexyl-
28、3-methyl-4-phenylpiperidine-4-carboxylic acidimpurity G(3S,4R)-1-cis-4-carbamoyl-4-(4-fluorophenyl)cyclohexyl-3-methyl-4-phenylpiperidine-4-carboxylic acidimpurity I(3S,4S)-1-cis-4-cyano-4-(4-fluorophenyl)cyclohexyl-3-methyl-4-phenylpiperidine-4-carboxylic acidimpurity K1-cis-4-cyano-4-(4-fluorophen
29、yl)cyclohexyl-3-methyl-4-phenylpyridiniumimpurity F(3S,4R)-3-methyl-4-phenylpiperidine-4-carboxylic acidimpurity H1-(4-fluorophenyl)-4-oxocyclohexanecarbonitrileimpurity J(3S,4R)-1-cis-4-cyano-4-(4-fluorophenyl)cyclohexyl-4-(3-hydroxyphenyl)-3-methylpiperidine-4-carboxylic acidimpurity L(3S,4R)-1-(1
30、S,4R)-4-cyano-3-(4-fluorophenyl)cyclohexyl-3-methyl-4-phenylpiperidine-4-carboxylic acid 1-oxide.方法解析: 原方法采用毛细管电泳色谱( CE)进行分析，重现性与稳定性较差，操作比较复杂。现方法改用 UPLC进行分析，分析时间缩短，可操作性大大提高。17富马酸喹硫平 Quetiapine fumarate 方法来源: 收载于 Pharmeuropa 24.4, October 2012, P119结构式: 有关物质:色谱柱: L11, 2.1 mm x 10 cm; 1.7 m (XSelect C
31、SH C6-phenyl)流动相: Buffer:3.85g/L乙酸铵，用氨水调至 pH9.0Solution A:甲醇 :buffer=10:90Solution B:乙腈梯度条件:柱温 : 50 C 流速 (ml/min): 0.5 波长 (nm): 240色谱图:Time (min) Solution A (%) Solution B (%)0 - 8 80 208 - 14.5 8060 204514.5 - 22.6 6050 405022.6 - 26 5030 507026 - 29 3010 709029 - 30 10 9018Name 相对保留时间 保留时间 可接受标准 (
32、%)impurity G 0.5 0.5 0.15quetiapine 1.0 - -impurity N 1.04 2.0 0.15单个未知杂质 - 1.0 0.10总杂质 - - 0.5杂质结构杂质谱:impurity A2-2-4-(dibenzob,f1,4thiazepin-11-yl)piperazin-1-ylethoxyethyl acetateimpurity C2-2-4-(dibenzob,f1,4thiazepin-11-yl)piperazin-1-ylethoxyethyl 4-(dibenzob,f1,4thiazepin-11-yl)piperazin-1-yl
33、acetateimpurity E11,11-ethylenebis(oxyethylenepiperazine-4,1-diyl)bis(dibenzob,f1,4thiazepine)impurity Gdibenzob,f1,4thiazepin-11(10H)-oneimpurity B11-(piperazin-1-yl)dibenzob,f1,4thiazepineimpurity D11,11-(piperazine-1,4-diyl)bis(dibenzob,f1,4thiazepine)impurity F2-(2-aminophenyl)sulfanylphenyl4-2-
34、(2-hydroxyethoxy)ethylpiperazin-1-ylmethanoneimpurity H2-2-4-(dibenzob,f1,4thiazepin-11-yl)-1-oxidopiperazin-1-ylethoxyethanol19杂质结构impurity I2-4-(dibenzob,f1,4thiazepin-11-yl)piperazin-1-ylethanolimpurity KN-2-2-4-2-(2-hydroxyethoxy)ethylpiperazin-1-ylcarbonylphenylsulfanylphenylacetamideimpurity N
35、2-2-4-2-2-4-(dibenzob,f1,4thiazepin-11-yl)piperazin-1-ylethoxyethylpiperazin-1-ylethoxyethanolimpurity P11-(4-ethylpiperazin-1-yl)dibenzob,f1,4thiazepineimpurity R(2E)-4-ethoxy-4-oxobut-2-enoic acidimpurity J2-2-2-2-4-(dibenzob,f1,4thiazepin-11-yl)piperazin-1-ylethoxyethoxyethoxyethanolimpurity L2-2
36、-4-(9-chlorodibenzob,f1,4thiazepin-11-yl)piperazin-1-ylethoxyethanolimpurity O11-4-2-2-(triphenylmethoxy)ethoxyethylpiperazin-1-yldibenzob,f1,4thiazepineimpurity Q4-(dibenzob,f1,4thiazepin-11-yl)-1,1-bis2-(2-hydroxyethoxy)ethylpiperazin-1-iumimpurity S2-2-4-(5-oxidodibenzob,f1,4thiazepin-11-yl)piper
37、azin-1-ylethoxyethanol20杂质结构impurity T11-(morpholin-4-yl)dibenzob,f1,4thiazepineimpurity V2-2-4-(phenanthridin-6-yl)piperazin-1-ylethoxyethanolimpurity Udibenzob,f1,4thiazepin-11-amineimpurity W11-(4-2-2-(dibenzob,f1,4thiazepin-11-yloxy)ethoxyethylpiperazin-1-yl)dibenzob,f1,4thiazepine方法解析: EP8.6新增各
38、论，采用 UPLC方法，实现高峰容量，快速分析。21琥铂酸索非那新 Solifenacin succinate 方法来源: 收载于 Pharmeuropa 26.2, April 2014, P302结构式: 有关物质:色谱柱: L1, 2.1 mm x 10 cm; 1.7 m (ACQUITY UPLC BEH Shield RP18)流动相: Buffer:0.6g磷酸铵至 1L水中，加 1.0ml二乙胺，用浓氨水调至 pH=11Solution A:乙腈 :Buffer=45:55Solution B:乙腈梯度条件:柱温 : 40 C 流速 (ml/min): 0.4 波长 (nm):
39、 215色谱图:Time (min) Solution A (%) Solution B (%)0 - 0.5 90 100.5 - 10.5 9068 103210.5 - 12.5 68 3222Name 相对保留时间 可接受标准 (%)impurity A 0.7 0.2solifenacin - -单个未知杂质 - 0.10总杂质 - 0.3杂质谱:杂质结构impurity A(1S)-1-phenyl-1,2,3,4-tetrahydroisoquinolineimpurity Cbis(1S)-1-phenyl-3,4-dihydroisoquinolin-2(1H)-ylmeth
40、anoneimpurity E(3R)-1-azabicyclo2.2.2octan-3-ol (3-quinuclidinol)impurity G(3R)-1-azabicyclo2.2.2oct-3-yl (1R)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylateimpurity Bpropan-2-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylateimpurity D(1R)-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl(1S)-1-
41、phenyl-3,4-dihydroisoquinolin-2(1H)-ylmethanoneimpurity F(3S)-1-azabicyclo2.2.2oct-3-yl (1R)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylateimpurity H(3S)-1-azabicyclo2.2.2oct-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate方法解析: EP8.6新增各论，采用 UPLC方法，实现高峰容量，快速分析。23硫酸羟氯喹 Hydroxychloroqu
42、ini sulfas方法来源: 收载于 Pharmeuropa 27.2, April 2015, P52结构式: 有关物质:色谱柱: L1, 2.1 mm x 5 cm; 1.7 m (Waters ACQUITY UPLC BEH C18)流动相: Buffer:1.36g磷酸二氢钾至 900ml水中，加 0.15g庚烷磺酸钠，用三乙胺调至 pH=7.0，加水至 1000mlSolution A:甲醇 :Buffer=10:90Solution B:甲醇 :Buffer=85:15梯度条件:流速 (ml/min): 0.7 波长 (nm): 254色谱图:Time (min) Soluti
43、on A (%) Solution B (%)0 - 1 90 101 - 12 9068 103224Name 相对保留时间 可接受标准 (%)impurity B 0.8 0.15impurity C 0.9 0.4hydroxychloroquine 1.0 -单个未知杂质 - 0.10总杂质 - 0.6杂质谱:杂质结构impurity A2-(4RS)-4-(7-chloroquinolin-4-yl)aminopentyl(ethyl)nitrorylethanolimpurity C2-(4RS)-4-(7-chloroquinolin-4-yl)aminopentylaminoe
44、thanolimpurity E(4R)-4-(7-chloroquinolin-4-yl)aminopentan-1-olimpurity G4,7-dichloroquinolineimpurity B2-(4RS)-4-(7-chloroquinolin-4-yl)aminopentyl(ethyl)aminoethyl hydrogen sulfateimpurity D(4RS)-N4-(7-chloroquinolin-4-yl)-N1-ethylpentane-1,4-diamineimpurity F7-chloro-4-(2-methylpyrrolidin-1-yl)qui
45、noline方法解析: 征求意见稿，采用 UPLC方法，实现高峰容量，快速分析。25多粘菌素 E 甲磺酸钠 Colistimethatum natricum方法来源: 收载于 Pharmeuropa 27.3, October 2015, P70结构式: 有关物质:色谱柱: L1, 2.1 mm x 15 cm; 1.7 m (Waters ACQUITY UPLC CSH)预柱： 2.1 mm 0.5-cm; 1.7-m流动相: Buffer:7.8g/L磷酸二氢钠至 980ml水中，用 1M氢氧化钠溶液调至 pH=6.5，加水至 1000mlSolution A:乙腈 :Buffer=5:
46、95Solution B:乙腈 :Buffer=50:50梯度条件:柱温 : 30 C 流速 (ml/min): 0.3 波长 (nm): 210 进样温度 : 5 CTime (min) Solution A (%) Solution B (%)0 - 10 8068 203210 - 35 6853 324735 - 36 5380 472036 - 44 80 2018 90 1026Name 相对保留时间 可接受标准 (%)CMS E2ASM8 0.22 0.5 - 2.0CMS E1ASM8 0.39 5.0 - 9.5CMS E2ASM6 0.71 0.5 - 2.5CMS E1A
47、SM6 1.0 6.5 - 9.5CMS E2ASM4 1.77 最大 1.5CMS E1ASM4 2.35 2.0 - 5.0总量 - 最少 7 7.0杂质谱:色谱图:方法解析: 征求意见稿，采用 UPLC方法，实现高峰容量，快速分析。27USP Drug Product Assay TestsOrganic Chemical Medicines方法来源: 收载于 USP39-NF34描述: OTC药物活性成分检测的鉴别及含量测定方法含量方法 1:色谱柱: L1, 2.1 mm x 15 cm; 1.8 m (ACQUITY UPLC HSS T3)流动相: Solution A:0.15%
48、三氟乙酸水溶液Solution B:0.02%三氟乙酸(乙腈 -甲醇 =75:25的混合溶液)梯度条件:柱温 : 40 C 流速 (ml/min): 0.4 波长 (nm): 见峰表色谱图( 225 nm):Time (min) Solution A (%) Solution B (%)0.0 90 100.6 90 102.3 77 235.5 77 237.4 57 438.0 57 4312.5 1 9913.5 1 99AU0.000.200.400.60Minutes0.00 3.50 7.00 10.50 14.00 17.5028Name 波长 ( nm) 保留时间 ( min)Phenylephrine 225 1.9Acetaminophen 254 2.7Caffeine 254 3.9Doxylamine 264 4.0Pseudoephedrine 210 4.1Chlorpheniramine 225 6.1Brompheniramine 264 7.0Aspirin 276 7.5Dextromethorphan 225 10.1Diphenhydramine 225 10.2峰表:杂质结构Phenylephrine CaffeinePseudo
