Curry S H, Brown E A, Kuck H, Cassin S
Can J Physiol Pharmacol. 1982 Jul;60(7):988-92. doi: 10.1139/y82-139.
Indomethacin is used in closure of the ductus arteriosus in newborn humans as well as in related research in near-term sheep and goats. Conflicting data in these studies have led to a reexamination of indomethacin stability. Solutions at various pH values, at two temperatures, and in polyethylene glycol (PEG-400), were assessed by high-pressure liquid chromatography for indomethacin and its products. Solutions below pH 7.4 were stable. Decomposition was rapid in alkaline solutions. Solutions at pH 7.4 showed no changes up to 24 h. Solutions of sodium indomethacin, and of indomethacin in PEG were stable. Solutions in aqueous Na2CO3 were variably stable depending on the mode of mixing. A solution prepared directly in 0.1 M Na2CO3 (pH 10.7) lost 75% of its content in 80 min; a similar solution diluted immediately with two volumes of pH 7.4 buffer (final pH 9.9) showed less decomposition. A solution in Na2CO3 adjusted to pH 7.4 with HCl was stable (at least 24 h). Solutions prepared by suspending indomethacin in 0.9% NaCl and adding Na2CO3 slowly were stable for 80 min; rapid mixing led to decomposition. Solutions in plasma were stable at -20 degrees C (2 months). Lack of indomethacin activity in some biological studies may have resulted from injection of inactive solutions.
吲哚美辛被用于人类新生儿动脉导管未闭的闭合治疗，以及近期对绵羊和山羊的相关研究中。这些研究中相互矛盾的数据促使人们重新审视吲哚美辛的稳定性。通过高压液相色谱法对吲哚美辛及其产物在不同pH值、两种温度以及聚乙二醇（PEG - 400）中的溶液进行了评估。pH值低于7.4的溶液是稳定的。在碱性溶液中分解迅速。pH值为7.4的溶液在24小时内无变化。吲哚美辛钠溶液以及吲哚美辛在PEG中的溶液是稳定的。在碳酸钠水溶液中的溶液稳定性因混合方式而异。直接在0.1M碳酸钠（pH 10.7）中配制的溶液在80分钟内损失了75%的含量；用两倍体积的pH 7.4缓冲液（最终pH 9.9）立即稀释的类似溶液分解较少。用盐酸将碳酸钠溶液调节至pH 7.4后是稳定的（至少24小时）。将吲哚美辛悬浮于0.9%氯化钠中并缓慢加入碳酸钠配制的溶液在80分钟内是稳定的；快速混合会导致分解。血浆中的溶液在-20摄氏度下稳定（2个月）。一些生物学研究中吲哚美辛活性的缺乏可能是由于注射了无活性的溶液所致。
