盐酸青藤碱水溶液的降解动力学研究

目的:研究盐酸青藤碱水溶液的降解动力学特征。方法:应用比色法确定盐酸青藤碱在不同pH值、不同离子强度、不同介电常数水溶液中经80℃恒温加速试验所得的降解动力学参数。结果:经过线性拟合对比分析,盐酸青藤碱水溶液的降解反应级数为n=1。降解速率常数(k)值随pH值的上升而增高,在pH<3的低pH值区域降解十分缓慢;而进入pH3.9～5的区域趋于稳定,出现一个较低的平台;当pH>5时,k值随pH值的上升而迅速增高。盐酸青藤碱水溶液随离子强度的增加,降解速率增加;溶液的介电常数增加,其降解速率也增加。结论:盐酸青藤碱水溶液的降解属于近似1级动力学过程,降解速率受溶液pH影响显著;降解速率与溶液离子强度成正相关,与溶液介电常数亦成正相关。     

盐酸阿莫罗芬在水溶液中的降解动力学研究

目的：研究盐酸阿莫罗芬在水溶液中的降解动力学。方法：建立HPLC法,测定盐酸阿莫罗芬在不同pH值、不同温度、不同离子强度的缓冲液中的降解动力学参数。结果：盐酸阿莫罗芬在水溶液中的降解呈现伪一级动力学特征,随着温度的增加,其降解速率增大;在37和60℃时,随着PH的增加,盐酸阿莫罗芬的降解速率明显增大（P〈0．05）,其半衰期和有效期明显减小（P〈0．05）,而随着离子强度的增大,其降解速率有所减小（P〉0．05）;在4和25℃时,盐酸阿莫罗芬在不同pH和不同离子强度的缓冲液中相对稳定;盐酸阿莫罗芬降解活化能随着pH的增大而增大。结论：盐酸阿莫罗芬在水溶液中的降解速率与温度、pH值和离子强度有关,其中温度对盐酸阿莫罗芬降解的影响较为明显。     

腺苷钴胺水溶液的光降解动力学研究

目的：考察腺苷钴胺水溶液的光降解动力学特征。方法：运用HPLC法测定水溶液中腺苷钴胺含量及有关物质。考察样品浓度、光强度、温度、pH对腺苷钴胺水溶液光稳定性的影响。结果：经线性拟合对比分析,腺苷钴胺溶液的光降解反应级数为n=1,腺苷钴胺溶液对光极敏感,在pH2．5—3．5的溶液中相对稳定,腺苷钴胺溶液的光降解随样品浓度的降低、光强度的升高而增加,恒温避光加速试验中腺苷钴胺溶液的光降解并不随温度的升高而升高,但恒温光照加速试验中温度的升高明显加速腺苷钴胺溶液的光降解。结论：腺苷钴胺溶液光降解属近似一级动力学过程,光降解速率受溶液pH影响显著,热可加速腺苷钴胺溶液的光降解。     

氟罗沙星在不同浓度溶液中的光降解动力学

目的:研究多种浓度的氟罗沙星溶液的光降解过程的差异以及影响其光降解速率的因素。方法:在相同光照条件下对不同的氟罗沙星溶液进行催化降解,用高效液相色谱法测定各溶液中氟罗沙星的浓度,绘制光降解动力学曲线,计算光降解动力学参数。同时考察pH、叠氮钠及氯化钠对氟罗沙星溶液光降解速率的影响。结果:低浓度的氟罗沙星溶液的光降解动力学过程符合一级动力学方程,而高浓度的氟罗沙星溶液光降解动力学过程符合零级动力学方程且溶液相对稳定。pH的变化会影响氟罗沙星溶液的光降解速率。叠氮钠的加入有抑制光降解的作用,而氯化钠的加入可使氟罗沙星产生新的光降解杂质。结论:高浓度的氟罗沙星溶液对光相对稳定,低pH和单线态氧猝灭剂的存在有利于提高氟罗沙星溶液对光的稳定性。该研究为氟罗沙星注射液的生产、储存和设计提供了理论指导和数据支持。     

HPLC法测定阿奇霉素在水溶液中的降解动力学

目的研究阿奇霉素在水溶液中的降解动力学,为阿奇霉素液体制剂的开发提供参考。方法通过经典恒温试验,应用HPLC法测定阿奇霉素在不同pH值、不同温度、不同离子强度、不同缓冲液条件下的降解动力学参数。结果阿奇霉素在水溶液中的降解呈现一级动力学特征,其最稳定pH值(pHm)为6.41;随着离子强度和温度的增加,阿奇霉素的降解加快;阿奇霉素在磷酸盐缓冲液中比在醋酸盐、枸橼酸盐缓冲液中相对稳定。结论阿奇霉素降解速率与溶液pH值、缓冲液种类、离子强度以及温度有关;溶液pH值与温度对阿奇霉素降解作用的影响较为明显。     

探讨光稳定性试验在上市药品质量标准研究中的应用

目的： 探讨光稳定性试验对上市药品质量标准研究的应用。方法： 按照ICH药物光稳定性试验指导原则，依据盐酸洛美沙星的质量标准，考察光强制破坏条件下，盐酸洛美沙星原料、片剂和胶囊剂的稳定性及其盐酸洛美沙星溶液的光降解动力学。。结果： 经HPLC检测可知，原料、片剂和胶囊剂直接光照15 d，固体样品主成分基本稳定；原料、片剂和胶囊剂的溶液光照24 h不稳定，有杂质产生；溶出度测定溶液光照24 h，降解动力学拟合符合0.5 级动力学方程；含量测定供试品溶液光照24 h，降解动力学拟合符合1级动力学方程。结论：光稳定性试验不仅可用于上市前的药品评价，亦可为上市药品质量标准研究提供数据支持。     

4种氟喹诺酮类抗生素水溶液的光稳定性研究

目的：探讨利用氟喹诺酮水溶液光降解动力学的特性，评价喹诺酮抗生素液体制剂的光稳定性。方法：比较4种氟喹诺酮水溶液在UVA光照下紫外光谱的变化；并根据HPLC法测定的光照过程中的含量，求出其光降解动力学参数t1/2。结果：3种氟喹诺酮的光降解过程符合一级动力学方程。溶液中光稳定性顺序为：司帕沙星，环丙沙星，左旋氧氟沙星，洛美沙星。结论：根据光降解动力学参数可较客观地评价喹诺酮抗生素液体制剂的光稳定性。     

盐酸左旋多巴甲酯水溶液稳定性研究

目的考察pH值对盐酸左旋多巴甲酯水溶液稳定性的影响。方法采用经典恒温加速试验法，考察不同温度下不同pH值对盐酸左旋多巴甲酯稳定性的影响，测定水解速率常数，活化能及最稳定时的pH值。结果在不同温度下，当pH=3．0时，盐酸左旋多巴甲酯水溶液最稳定；当pH〉3时，随着pH值升高，水溶液的稳定性降低。结论适当调整溶液的pH值，可以改善盐酸左旋多巴甲酯的化学稳定性。     

新鱼腥草素钠水溶液的降解动力学研究

采用HPLC法研究了新鱼腥草素钠在不同pH缓冲液中的降解动力学特征。动力学拟合线性分析表明，新鱼腥草素钠在pH4．0-11．0范围内的降解反应均符合二级动力学规律，降解速率K受pH影响显著，pH-K曲线呈钟罩形；在pH7．0-8．0的溶液中降解速率最快，在pH4．0及pH11．0的溶液中新鱼腥草素钠相对较稳定。提示新鱼腥草素钠在水溶液中的降解并非简单的酸碱催化反应，在特定的pH范围内，存在控速的反应步骤。     

尼索地平光解动力学和pH值对稳定性影响的研究

目的：考察尼索地平光解动力学和pH值对稳定性的影响。方法：采用HPLC法测定尼索地平浓度、并考察不同浓度尼索地平光解动力学及不同pH条件下尼索地平甲醇溶液的稳定性。结果：经指数衰减非线性回归分析，低浓度尼索地平甲醇溶液的光解反应级数n=1；尼索地平在pH3．2—7．9下避光放置，未见光解产物。结论：尼索地平甲醇溶液光降解属一级动力学过程；尼索地平在pH3．2-7．9间稳定。     

Chemical kinetics and aqueous degradation pathways of a new class of synthetic ozonide antimalarials

Chemical stability of a new class of ozonide (1,2,4 trioxolanes) antimalarial compounds was investigated. The effects of pH, ionic strength, dielectric constant and cyclodextrin-complexation on the chemical stability and degradation product formation of selected compounds were examined. The mechanism of degradation in aqueous solution was probed using (18)O-labelled water and kinetic solvent isotope effect studies. The effect of stereochemistry was investigated using selected pairs of stereoisomers. The degradation of the ozonides in aqueous solution followed apparent first-order kinetics, with no effect of ionic strength and no indication of any direct involvement of water in the degradation mechanism. All major degradation products were identified and mass balance was confirmed. Stereochemistry had a significant effect on degradation rate; trans isomers degrading approximately four-fold faster than the corresponding cis isomers. The degradation rates were essentially independent of pH above pH 2; however, an additional specific acid catalysed pathway was dominant below pH 2. Solvent dielectric constant had a significant effect on the degradation rate. It is proposed that the degradation observed in aqueous solution occurred through a concerted heterolytic scission of the central ozonide ring, with chemical substituents on the cyclohexyl ring having only a minor influence on degradation rate.     

盐酸洛美沙星光降解的部分杂质研究

目的确定控制盐酸洛美沙星光降解杂质的必要性。方法用液相色谱/质谱联用技术分离并鉴定盐酸洛美沙星的两个光降解杂质,并化学合成了两个化合物:脱羧洛美沙星[（±）-1-乙基-6,8-二氟-1,4-二氢-7-（3-甲基-1-哌嗪基）-4-氧代喹啉（简称DCLM）]和氯代洛美沙星[（±）-1-乙基-6-氟-8-氯-1,4-二氢-7-（3-甲基-1-哌嗪基）-4-氧代喹啉-3-羧酸（简称CLLM）]。比较DCLM和CLLM与盐酸洛美沙星相应光降解杂质的液相色谱和质谱。测试洛美沙星、DCLM及CLLM体外细胞毒性。结果化学合成的DCLM和CLLM的液相色谱和质谱分析结果分别与盐酸洛美沙星相应光降解杂质一致。洛美沙星、DCLM和CLLM的IC₅₀分别为1.9mmol/L,2.2mmol/L,0.7mmol/L。结论确证了盐酸洛美沙星的两个光降解杂质分别为:DCLM和CLLM。DCLM的体外细胞毒性与洛美沙星相近;CLLM的体外细胞毒性显著强于洛美沙星,可能是导致洛美沙星临床不良反应的物质。     

Stability of batanopride hydrochloride in aqueous solutions.

The degradation of batanopride hydrochloride, an investigational antiemetic drug, was studied in aqueous buffer solutions (pH 2-10; ionic strength, 0.5; 56 degrees C) in an attempt to improve drug stability for parenteral administration. Degradation occurs by two different mechanisms depending on the pH of the solution. In acidic media (pH 2-6), the predominant reaction was intramolecular cyclization followed by dehydration to form a 2,3-dimethylbenzofuran. There was no kinetic or analytical (high-performance liquid chromatography) evidence for the formation of an intermediate; therefore, the rate of dehydration must have been very rapid compared with the rate of cyclization. In alkaline media (pH 8-10), the primary route of degradation was cleavage of the C-O alkyl ether bond. In the intermediate pH range (pH 6-8), both reactions contributed to the overall degradation. Both degradation reactions followed apparent first-order kinetics. The pH-rate profile suggests that batanopride hydrochloride attains its optimal stability at pH 4.5-5.5. Citrate buffer was catalytic at pH 3 and 5, and phosphate buffer was catalytic at pH 8. No catalytic effect was observed for the borate buffer at pH 9-10.     

The stability of oxymetazoline hydrochloride in aqueous solution

The kinetics of the hydrolysis reaction of oxymetazoline hydrochloride in aqueous solution at three temperatures (343 K, 353 K, 363 K), over the pH-range 0.5-12.5 and ionic strength 0.5 has been investigated. The changes of concentration of oxymetazoline hydrochloride were followed by the HPLC method with UV detection. In the pH range from 0.45 to 12.50, the hydrolysis of oxymetazoline consists of hydrolysis of oxymetazoline molecules catalyzed by hydrogen ions, spontaneous hydrolysis of the dissociated and undissociated oxymetazoline molecules. A minimal rate of the hydrolysis oxymetazoline was observed to occur in the pH range from 2.0 to 5.0. Thermodynamic parameters of the reaction: energy, entropy and enthalpy of activation and the frequency factor for the specific rate constants were determined.     

Degradation kinetics of phentolamine hydrochloride in solution

The degradation kinetics of phentolamine hydrochloride in aqueous solution over a pH range of 1.2 to 7.2 and its stability in propylene glycol- or polyethylene glycol 400-based solutions were investigated. The observed rate constants were shown to follow apparent first-order kinetics in all cases. The pKa determination for phentolamine hydrochloride was found to be 9.55 +/- 0.10 (n = 5) at 25 +/- 0.2 degrees C. This indicated the protonated form of phentolamine occurs in the pH range of this study. The pH-rate profile indicated a pH-independent region (pH 3.1-4.9) exists with a minimum rate around pH 2.1. The catalytic effect of acetate and phosphate buffer species is ordinary. The catalytic rate constants imposed by acetic acid, acetate ion, dihydrogen phosphate ion, and monohydrogen phosphate ion were determined to be 0.018, 0.362, 0.036, and 1.470 L mol-1 h-1, respectively. The salt effect in acetate and phosphate buffers followed the modified Debye-Huckel equation quite well. The ZAZB value obtained from the experiment closely predicts the charges of the reacting species. The apparent energy of activation was determined to be 19.72 kcal/mol for degradation of phentolamine hydrochloride in pH 3.1, 0.1 M acetate buffer solution at constant ionic strength (mu = 0.5). Irradiation with 254 nm UV light at 25 +/- 0.2 degrees C showed a ninefold increase in the degradation rate compared with the light-protected control. Propylene glycol had little or no effect on the degradation of phentolamine hydrochloride at 90 +/- 0.2 degrees C; however, polyethylene glycol 400 had a definite effect.