CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal; CBQF - Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa/Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal; Centro de Química Medicinal da Universidade do Porto (CEQUIMED-UP), Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
REQUIMTE, Instituto Superior de Engenharia do Porto, Instituto Politécnico do Porto, Rua Dr. António Bernardino de Almeida, 431, 4200-072 Porto, Portugal; CIIMAR/CIMAR-Interdisciplinary Centre of Marine and Environmental Research, Laboratory of Environmental Toxicology, University of Porto, Rua dos Bragas, 289, 4050-123 Porto, Portugal.
J Chromatogr A. 2014 Oct 10;1363:226-35. doi: 10.1016/j.chroma.2014.06.099. Epub 2014 Jul 8.
The interest for environmental fate assessment of chiral pharmaceuticals is increasing and enantioselective analytical methods are mandatory. This study presents an enantioselective analytical method for the quantification of seven pairs of enantiomers of pharmaceuticals and a pair of a metabolite. The selected chiral pharmaceuticals belong to three different therapeutic classes, namely selective serotonin reuptake inhibitors (venlafaxine, fluoxetine and its metabolite norfluoxetine), beta-blockers (alprenolol, bisoprolol, metoprolol, propranolol) and a beta2-adrenergic agonist (salbutamol). The analytical method was based on solid phase extraction followed by liquid chromatography tandem mass spectrometry with a triple quadrupole analyser. Briefly, Oasis MCX cartridges were used to preconcentrate 250 mL of water samples and the reconstituted extracts were analysed with a Chirobiotic V under reversed mode. The effluent of a laboratory-scale aerobic granular sludge sequencing batch reactor (AGS-SBR) was used to validate the method. Linearity (r(2)>0.99), selectivity and sensitivity were achieved in the range of 20-400 ngL(-1) for all enantiomers, except for norfluoxetine enantiomers which range covered 30-400 ngL(-1). The method detection limits were between 0.65 and 11.5 ngL(-1) and the method quantification limits were between 1.98 and 19.7 ngL(-1). The identity of all enantiomers was confirmed using two MS/MS transitions and its ion ratios, according to European Commission Decision 2002/657/EC. This method was successfully applied to evaluate effluents of wastewater treatment plants (WWTP) in Portugal. Venlafaxine and fluoxetine were quantified as non-racemic mixtures (enantiomeric fraction ≠ 0.5). The enantioselective validated method was able to monitor chiral pharmaceuticals in WWTP effluents and has potential to assess the enantioselective biodegradation in bioreactors. Further application in environmental matrices as surface and estuarine waters can be exploited.
对手性药物环境归宿评估的兴趣日益增加，对具有对映选择性的分析方法的需求也日益增加。本研究提出了一种用于定量分析七种对映体药物对映体和一种代谢物对映体的对映选择性分析方法。所选手性药物属于三个不同的治疗类别，即选择性 5-羟色胺再摄取抑制剂（文拉法辛、氟西汀及其代谢物去甲氟西汀）、β-受体阻滞剂（阿普洛尔、比索洛尔、美托洛尔、普萘洛尔）和β2-肾上腺素能激动剂（沙丁胺醇）。该分析方法基于固相萃取，随后采用带有三重四极杆分析器的液相色谱串联质谱法。简要地说，Oasis MCX 小柱用于预浓缩 250 mL 水样，经反相模式分析后用 Chirobiotic V 进行分析。采用实验室规模好氧颗粒污泥序批式反应器（AGS-SBR）的流出物对该方法进行了验证。除去甲氟西汀对映体的线性范围为 30-400ng/L 外，所有对映体的线性范围（r(2)>0.99）、选择性和灵敏度均在 20-400ng/L 之间。方法检出限在 0.65-11.5ng/L 之间，方法定量限在 1.98-19.7ng/L 之间。根据欧洲委员会第 2002/657/EC 号决定，使用两个 MS/MS 跃迁和离子比确认所有对映体的身份。该方法成功地应用于评估葡萄牙废水处理厂（WWTP）的出水。文拉法辛和氟西汀被定量为非外消旋混合物（对映体分数≠0.5）。经验证的对映选择性方法能够监测 WWTP 出水中的手性药物，并且有可能评估生物反应器中的对映选择性生物降解。还可以进一步将其应用于环境基质，如地表水和河口水域。
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