芳酸及其酯类.ppt

第六章 芳酸及其酯类药物的分析;概述;第一节　典型药物分类与理化性质分类 ;（一）. 水杨酸类 1. 典型药物 ;双水杨酯;;阿司匹林 Aspirin CAS 50-78-2 Dissociation Constant: pKa3.38 ( 25° ,? 1M KCl) Partition Coefficient (Calculated): Log P 1.02(calc) White monoclinic tablets or needle-like crystals. d 1.40. mp 135° (rapid heating); the melt solidifies at 118°. uv max (0.1N H2SO4): 229 nm (E1%1cm 484); (CHCl3): 277 nm (E1%1cm 68). Is odorless, but in moist air it is gradually hydrolyzed into salicylic and acetic acids and acquires the odor of acetic acid. Stable in dry air. pK (25°) 3.49. One gram dissolves in 300 ml water at 25°, in 100 ml water at 37°, in 5 ml alcohol, 17 ml chloroform, 10-15 ml ether. Less soluble in anhydr ether. Decomp by boiling water or when dissolved in solns of alkali hydroxides and carbonates. Inorganic salts of acetylsalicylic acid are soluble in water (esp the Ca salt, q.v.), but are decomposed quickly. LD50 orally in mice, rats: 1.1, 1.5 g/kg (Hart). ;二氟尼柳 diflunisal CAS 22494-42-4 Log P 4.39 White, crystals from toluene, mp 211-213°. Freely sol in alc, methanol; sol in most organic solvents, ethyl acetate, acetone; slightly sol in chloroform, carbon tetrachloride, methylene chloride. Practically insol in water at neutral or acidic pH. Insol in hexane. LD50 orally in female mice: 439 mg/kg (Stone). ;双水杨酸酯 salsalate White, crystals from toluene, mp 211-213°. Freely sol in alc, methanol; sol in most organic solvents, ethyl acetate, acetone; slightly sol in chloroform, carbon tetrachloride, methylene chloride. Practically insol in water at neutral or acidic pH. Insol in hexane. LD50 orally in female mice: 439 mg/kg (Stone). ;;2. 主要性质（1）酸性：a. 芳酸类药物分子中具有－COOH，显弱酸性，可用酸碱滴定法测定含量b. 药用芳酸pKa在3～6之间;;无游离-COOH，有Ar－，可用UV法 具有芳伯氨基，可采用亚硝酸钠滴定法。 具有酚羟基，与Fe3＋生成有色的物质 水杨酸酯类易水解，产生特殊杂质;（二）. 苯甲酸类 1. 代表药物 ;2.主要性质;（三）其他芳酸类;2. 性质;一 与FeCl3反应 1. 水杨酸及其盐;+; FeCl3T.S;3、双水杨酯;NaOH;4. 氯贝丁酯;二、重氮化-偶合反应 ;三、水解反应 ;四. 分解产物的反应; 六、紫外吸收光谱法 七、红外吸收光谱法 ;第三节　特殊杂质检查;乙酰化;2、溶液的澄清度检查 检查碳酸钠 试液中不溶物 ;3、