Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33.600, 28871, Alcalá de Henares (Madrid), Spain.
Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33.600, 28871, Alcalá de Henares (Madrid), Spain; Madrid Institute for Advanced Studies of Water (IMDEA Agua), Parque Científico Tecnológico, E-28805, Alcalá de Henares (Madrid), Spain.
J Hazard Mater. 2019 Jul 15;374:203-210. doi: 10.1016/j.jhazmat.2019.04.027. Epub 2019 Apr 5.
Stability and toxicity studies for duloxetine and econazole were achieved using individual solutions and their mixtures. Stability of drugs racemates and enantiomers was investigated under abiotic and biotic conditions. Toxicity was evaluated for the first time on Spirodela polyrhiza. EC50 values were calculated for each individual drug and for their binary mixture. Real (not nominal) concentrations determined by Capillary Electrophoresis were employed in the calculations of toxicity parameters. The use of a 25 mM phosphate buffer (pH 3.0) with 1.5% S-β-CD as chiral selector at a temperature of 30 °C and a separation voltage of -20 kV enabled the simultaneous enantiomeric separation of duloxetine and econazole in 7.5 min with enantiomeric resolutions of 7.9 and 6.5, respectively. For individual solutions, decay percentages under abiotic conditions were higher for duloxetine (80%) than for econazole (60%), while in presence of Spirodela polyrhiza they increased for duloxetine but not for econazole. Econazole showed the highest decay percentages under abiotic or biotic conditions (100%) in binary mixtures. EC50 values for duloxetine and econazole enabled to include both drugs within the group of very toxic compounds although econazole showed a higher toxicity than duloxetine and the binary mixture.
采用单一溶液及其混合物的方法,对度洛西汀和依康唑进行了稳定性和毒性研究。在非生物和生物条件下,研究了药物外消旋体和对映异构体的稳定性。首次在大漂上评价了毒性。计算了每种药物及其二元混合物的 EC50 值。通过毛细管电泳确定的实际(非标称)浓度用于毒性参数的计算。在 30°C 的温度下,使用 25mM 磷酸盐缓冲液(pH 3.0)和 1.5% S-β-CD 作为手性选择剂,并施加-20 kV 的分离电压,能够在 7.5 分钟内同时对度洛西汀和依康唑进行对映体分离,对映体分辨率分别为 7.9 和 6.5。对于单一溶液,非生物条件下度洛西汀(80%)的衰减百分比高于依康唑(60%),而在大漂存在的情况下,度洛西汀的衰减百分比增加,但依康唑没有增加。依康唑在二元混合物中,无论在非生物或生物条件下,衰减百分比均最高(100%)。度洛西汀和依康唑的 EC50 值使这两种药物都属于极毒化合物,尽管依康唑的毒性高于度洛西汀,且二元混合物的毒性更高。