Eap C B, Koeb L, Baumann P
Département Universitaire de Psychiatrie Adulte (DUPA), Prilly-Lausanne, Switzerland.
J Pharm Biomed Anal. 1993 Jun;11(6):451-7. doi: 10.1016/0731-7085(93)80157-v.
Although the sensitivity to light of thioridazine and its metabolites has been described, the problem does not seem to be widely acknowledged. Indeed, a survey of the literature shows that assays of these compounds under light-protected conditions have been performed only in a few of the numerous analytical studies on this drug. In the present study, thioridazine, its metabolites, and 18 other neuroleptics were tested for their sensitivity to light under conditions used for their analysis. The results show that light significantly affects the analysis of thioridazine and its metabolites. It readily causes the racemization of the isomeric pairs of thioridazine 5-sulphoxide and greatly decreases the concentration of thioridazine. This sensitivity to light varied with the medium used (most sensitive in acidic media) and also with the molecule (in order of decreasing sensitivity: thioridazine > mesoridazine > sulforidazine). Degradation in neutral or basic media was slow, with the exception of mesoridazine in a neutral medium. Twelve other phenothiazines tested, as well as chlorprotixene, a thioxanthene drug, were found to be sensitive to light in acidic media, whereas flupenthixol and zuclopenthixol (two thioxanthenes), clozapine, fluperlapine, and haloperidol (a butyrophenone) did not seem to be affected. In addition to being sensitive to light, some compounds may be readily oxidized by peroxide-containing solvents.
尽管已有人描述过硫利达嗪及其代谢物对光的敏感性，但这个问题似乎并未得到广泛认可。确实，一项文献调查显示，在众多关于此药物的分析研究中，只有少数几项研究在光保护条件下对这些化合物进行了测定。在本研究中，在用于分析硫利达嗪、其代谢物以及其他18种抗精神病药物的条件下，测试了它们对光的敏感性。结果表明，光会显著影响硫利达嗪及其代谢物的分析。它很容易导致硫利达嗪5 - 亚砜的异构体对发生消旋化，并大大降低硫利达嗪的浓度。这种对光的敏感性会因所用介质（在酸性介质中最敏感）以及分子不同而有所变化（按敏感性降低顺序排列：硫利达嗪＞美索达嗪＞舒必利）。除了在中性介质中的美索达嗪外，在中性或碱性介质中的降解速度较慢。测试的其他12种吩噻嗪类药物以及噻吨类药物氯丙硫蒽在酸性介质中对光敏感，而氟哌噻吨和珠氯噻醇（两种噻吨类药物）、氯氮平、氟哌拉平以及氟哌啶醇（一种丁酰苯类药物）似乎不受影响。除了对光敏感外，一些化合物可能很容易被含过氧化物的溶剂氧化。
