Khattak S U R, Sheikh D, Ahmad I, Usmanghani K
Faculty of Pharmacy, Hamdard University, Shahra-e-Madinat Al-Hikmah, Muhammad Bin Qasim Avenue, Karachi-74600, Pakistan.
Indian J Pharm Sci. 2012 Mar;74(2):133-40. doi: 10.4103/0250-474X.103845.
The effect of pH, media, phosphate concentration and ionic strength on the kinetics of thermal degradation of betamethasone valerate and betamethasone dipropionate has been investigated. A validated HPLC method has been used to determine the parent compounds and their major thermal degradation products identified in the reaction. Betamethasone-17-valerate gave rise to two major products, namely, betamethasone-21-valerate and betamethasone alcohol, and betamethasone dipropionate degraded into three major products, namely, betamethasone-17-propionate, betamethasone-21-propionate and betamethasone alcohol, in different media. Betamethasone valerate showed maximum stability at pH 4-5 while betamethasone dipropionate was maximally stable at pH 3.5-4.5. The degradation of betamethasone valerate and betamethasone dipropionate was found to follow first-order kinetics and the apparent first-order rate constants (k(obs)) for thermal degradation in different media range from 0.399-9.07×10(-3) h(-1) and 0.239-1.87×10(-3) h(-1), respectively. The values of the rate constants decrease with increasing solvent polarity, phosphate concentration and ionic strength. The second-order rate constants (k΄) for the phosphate ion inhibited reactions lie in the range of 3.02-1.30×10(-6) M(-1) s(-1).
研究了pH值、介质、磷酸盐浓度和离子强度对戊酸倍他米松和二丙酸倍他米松热降解动力学的影响。采用经过验证的高效液相色谱法测定反应中鉴定出的母体化合物及其主要热降解产物。在不同介质中，17-戊酸倍他米松产生两种主要产物，即21-戊酸倍他米松和倍他米松醇，二丙酸倍他米松降解为三种主要产物，即17-丙酸倍他米松、21-丙酸倍他米松和倍他米松醇。戊酸倍他米松在pH 4 - 5时表现出最大稳定性，而二丙酸倍他米松在pH 3.5 - 4.5时最稳定。发现戊酸倍他米松和二丙酸倍他米松的降解遵循一级动力学，不同介质中热降解的表观一级速率常数（k(obs)）分别为0.399 - 9.07×10(-3) h(-1)和0.239 - 1.87×10(-3) h(-1)。速率常数的值随着溶剂极性、磷酸盐浓度和离子强度的增加而降低。磷酸盐离子抑制反应的二级速率常数（k΄）在3.02 - 1.30×10(-6) M(-1) s(-1)范围内。
