Azuma Takashi, Ishida Mao, Hisamatsu Kanae, Yunoki Ayami, Otomo Kana, Kunitou Mari, Shimizu Mai, Hosomaru Kaori, Mikata Shiori, Mino Yoshiki
Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Chemosphere. 2017 Aug;180:476-482. doi: 10.1016/j.chemosphere.2017.04.040. Epub 2017 Apr 10.
A new enzymatic assay method that uses deconjugation enzymes was developed to evaluate the presence and extent of conjugated pharmaceuticals in the form of glucuronide conjugates or sulphate conjugates in river environments. First, acetaminophen glucuronide (Ace Glu) and acetaminophen sulphate (Ace Sul) were used as model conjugated pharmaceuticals to determine the appropriate combination of deconjugation enzymes and reaction conditions, including temperature, duration and pH. Next, we applied the defined method to 19 pharmaceuticals grouped into nine therapeutic classes that were chosen based on previously detected levels and frequencies in sewage and river water. The enzymatic decomposition profile varied widely depending upon the enzyme preparations available. The effect of the water reaction temperature was small between 5 and 40 °C, and the reaction proceeded in for both glucuronide conjugates and sulphate conjugates at an approximately neutral pH (corresponding to usual river water conditions) within 1 h. Application of the method to environmental samples showed that some pharmaceuticals were present in both glucuronide conjugate and sulphate conjugated forms, although glucuronide conjugates were the primary forms in the river water environment. Water treatment systems at sewage treatment plants were found to be effective for the removal of these conjugated compounds. The present results should be valuable in the environmental risk assessment of conjugated pharmaceuticals and in keeping river environments clean. To the best of our knowledge, this is the first report that enables the evaluation of the pharmaceutical deconjugation potential in a river environment.
开发了一种使用去结合酶的新型酶促测定方法，以评估河流环境中葡萄糖醛酸苷共轭物或硫酸盐共轭物形式的共轭药物的存在情况和程度。首先，对乙酰氨基酚葡萄糖醛酸苷（Ace Glu）和对乙酰氨基酚硫酸盐（Ace Sul）用作模型共轭药物，以确定去结合酶与反应条件（包括温度、持续时间和pH值）的合适组合。接下来，我们将所定义的方法应用于19种药物，这些药物分为九个治疗类别，是根据先前在污水和河水中检测到的水平和频率选择的。酶促分解情况因可用的酶制剂而异。水反应温度在5至40°C之间时影响较小，并且在大约中性pH值（对应于通常的河水条件）下，葡萄糖醛酸苷共轭物和硫酸盐共轭物的反应在1小时内均可进行。将该方法应用于环境样品表明，尽管葡萄糖醛酸苷共轭物是河水环境中的主要形式，但一些药物同时以葡萄糖醛酸苷共轭物和硫酸盐共轭物形式存在。发现污水处理厂的水处理系统对去除这些共轭化合物有效。目前的结果对于共轭药物的环境风险评估以及保持河流环境清洁具有重要价值。据我们所知，这是第一份能够评估河流环境中药物去结合潜力的报告。
