Kristensen S, Nord K, Orsteen A L, Tønnesen H H
Department of Pharmaceutics, Institute of Pharmacy, University of Oslo, Norway.
Pharmazie. 1998 Feb;53(2):98-103.
The influence of molecular oxygen and oxygen radicals on the photoreactivity of the antimalarial drug primaquine (PQ) has been investigated. Oxygen is directly involved in photodecomposition of the drug. Flushing with helium gas prior to and during irradiation to suppress the oxygen level of the medium, retards the degradation rate of PQ (followed by HPLC) and leads to the formation of only two degradation products (identified by MS) compared to eight main- and several minor products under normal atmospheric conditions. Flushing with oxygen gas prior to and during irradiation to increase the oxygen content of the medium accelerates the degradation rate of PQ. PQ produces oxygen radicals (hydroxyl and superoxide) during photolysis, while the photoproducts of PQ seem likely to induce singlet oxygen formation (detected by addition of radical scavengers). Sensitization reactions involving singlet oxygen lead to decomposition of PQ (followed by HPLC). On the basis of our results, photochemical reaction mechanisms of PQ are postulated and discussed. At physiological conditions (aqueous, neutral pH, oxygen rich) PQ has a large potential to decompose after light absorption. The photoreaction seems to be initiated at the quinoline nitrogen. The ability to form an intramolecular hydrogen bond seems to be essential for the luminescence properties of the drug. Phosphorescence lifetime of PQ is about 5 microseconds. Fast chemical reactions may occur from the short-lived triplet state of the drug, but the excited compound can diffuse only a limited distance prior to deexcitation. This can be important concerning light-induced adverse effects which may appear after medication with PQ.
已研究了分子氧和氧自由基对抗疟药物伯氨喹（PQ）光反应活性的影响。氧直接参与该药物的光分解过程。在辐照之前及辐照过程中用氦气吹扫以降低介质中的氧含量，可减缓PQ的降解速率（通过高效液相色谱法监测），与在正常大气条件下形成八个主要降解产物和几个次要降解产物相比，此时仅形成两个降解产物（通过质谱法鉴定）。在辐照之前及辐照过程中用氧气吹扫以增加介质中的氧含量，则会加速PQ的降解速率。PQ在光解过程中会产生氧自由基（羟基自由基和超氧阴离子），而PQ的光产物似乎可能诱导单线态氧的形成（通过添加自由基清除剂检测）。涉及单线态氧的敏化反应会导致PQ分解（通过高效液相色谱法监测）。基于我们的研究结果，推测并讨论了PQ的光化学反应机理。在生理条件下（水性、中性pH、富氧），PQ在吸收光后有很大的分解潜力。光反应似乎是在喹啉氮处引发的。形成分子内氢键的能力似乎对该药物的发光性质至关重要。PQ的磷光寿命约为5微秒。该药物的短寿命三重态可能会发生快速化学反应，但激发态化合物在去激发之前只能扩散有限的距离。这对于服用PQ后可能出现的光致不良反应而言可能很重要。
