Reaction of β-blockers and β-agonist pharmaceuticals with aqueous chlorine. Investigation of kinetics and by-products by liquid chromatography quadrupole time-of-flight mass spectrometry
Reaction of β-blockers and β-agonist pharmaceuticals with aqueous chlorine. Investigation of kinetics and by-products by liquid chromatography quadrupole time-of-flight mass spectrometry
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DOI：
10.1007/s00216-011-5707-7
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发表时间：
2012-06-01
影响因子：
4.3
通讯作者：
Cela, Rafael
中科院分区：
文献类型：
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作者：
Benito Quintana, Jose;Rodil, Rosario;Cela, Rafael
用液质联用(LC-MS)研究了两种β受体阻滞剂(阿替洛尔和心得安)和一种β受体激动剂(沙丁胺醇)在水氯化过程中的降解。精确质量四极飞行时间系统(QTOF)被用来跟踪药物的时间进程，并用于副产物的鉴定。采用Box-Behnken实验设计，研究了不同浓度的氯、溴和样品pH条件下药物的降解动力学。根据这些因素，阿替洛尔的半衰期为68-145小时，沙丁胺醇为1.3-33分钟，普奈洛尔为42-8362分钟。通常情况下，氯用量和pH值的增加会导致这些药物更快的降解。此外，水样中溴的存在也导致低氯剂量下阿替洛尔的转化速度更快。使用准确质量的高分辨率LC-QTOF-MS系统，共鉴定了14种副产物。β-受体阻滞剂/激动剂的转化途径主要包括卤代、羟化和脱烷基化。此外，这些副产品中的许多都是稳定的，这取决于所采用的氯化操作参数。
The degradation of two beta-blockers (atenolol and propranolol) and one beta-receptor agonist (salbutamol) during water chlorination was investigated by liquid chromatography-mass spectrometry (LC-MS). An accurate-mass quadrupole time-of-flight system (QTOF) was used to follow the time course of the pharmaceuticals and also used in the identification of the by-products. The degradation kinetics of these drugs was investigated at different concentrations of chlorine, bromide and sample pH by means of a Box-Behnken experimental design. Depending on these factors, dissipation half-lives varied in the ranges 68-145 h for atenolol, 1.3-33 min for salbutamol and 42-8362 min for propranolol. Normally, an increase in chlorine dosage and pH resulted in faster degradation of these pharmaceuticals. Moreover, the presence of bromide in water samples also resulted in a faster transformation of atenolol at low chlorine doses. The use of an accurate-mass high-resolution LC-QTOF-MS system permitted the identification of a total of 14 by-products. The transformation pathway of beta-blockers/agonists consisted mainly of halogenations, hydroxylations and dealkylations. Also, many of these by-products are stable, depending on the chlorination operational parameters employed.