Dual enantioselective LC-MS/MS method to analyse chiral drugs in surface water: Monitoring in Douro River estuary

Maria Miguel Coelho; Ana Rita Lado Ribeiro; João C G Sousa; Cláudia Ribeiro; Carla Fernandes; Adrián M T Silva; Maria Elizabeth Tiritan

doi:10.1016/j.jpba.2019.03.032

Dual enantioselective LC-MS/MS method to analyse chiral drugs in surface water: Monitoring in Douro River estuary

J Pharm Biomed Anal. 2019 Jun 5:170:89-101. doi: 10.1016/j.jpba.2019.03.032. Epub 2019 Mar 15.

Authors

Maria Miguel Coelho¹, Ana Rita Lado Ribeiro², João C G Sousa³, Cláudia Ribeiro⁴, Carla Fernandes⁵, Adrián M T Silva³, Maria Elizabeth Tiritan⁶

Affiliations

¹ CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal; Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia da Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal.
² Laboratory of Separation and Reaction Engineering - Laboratory of Catalysis and Materials (LSRE-LCM), Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: ritalado@fe.up.pt.
³ Laboratory of Separation and Reaction Engineering - Laboratory of Catalysis and Materials (LSRE-LCM), Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
⁴ CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal; Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, s/n, 4450-208 Matosinhos, Portugal.
⁵ Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia da Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal; Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, s/n, 4450-208 Matosinhos, Portugal.
⁶ CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal; Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia da Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal; Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, s/n, 4450-208 Matosinhos, Portugal. Electronic address: elizabeth.tiritan@iucs.cespu.pt.

PMID: 30909058
DOI: 10.1016/j.jpba.2019.03.032

Abstract

This work presents the development of an enantioselective method to quantify chiral drugs (CDs) in surface water and its application in the Douro River estuary monitoring. Different classes of CDs were targeted, including 23 compounds, namely beta-blockers, antidepressants, one beta₂-adrenergic agonist, non-steroidal anti-inflammatory drugs, stimulants, and some illicit drugs as cocaine (COC) and its metabolites, and amphetamines. The analytical method was based on an innovative application of solid phase extraction (SPE), followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a triple quadrupole analyzer. The ground-breaking approach of SPE consists in the use of Oasis^® MCX cartridges to pre-concentrate 500 mL of water samples, allowing the simultaneous extraction of acidic, basic and neutral analytes, rather than the conventional recovery of basic compounds only. Two chiral columns were used for enantiomeric separation in reverse elution mode, a Chirobiotic™V and a Pirkle type Whelk-O^®1, for basic and acidic compounds, respectively. The method validation demonstrated good linearity (r² > 0.99), selectivity and sensitivity, with method detection limits between 0.01 and 2.66 ng L^-1 and method quantification limits between 0.02 and 5.71 ng L^-1. The developed method was successfully applied to monitor daily variations along one week in surface waters collected in 5 locations of the Douro River estuary. Tramadol (TRM) and its metabolite N-desmethyltramadol (NDT), presented high concentrations near the affluent of a tributary river, while the second eluted enantiomer of O-desmethyltramadol (ODT) was found at high concentrations at the mouth of the Douro River. The metabolite NDT was quantified at higher concentrations than TRM. Venlafaxine (VNF) was found at high concentrations near the affluent of the same tributary river, but its metabolite, O-desmethylvenlafaxine (ODV), was found at concentrations 3 times higher. COC was found every day at all sampling points along the estuary, with slight variations.

Keywords: Chiral columns; Enantiomeric fraction; Illegal drug; Pharmaceutical; River water; Wastewater.

MeSH terms

Chromatography, Liquid / methods
Illicit Drugs / chemistry*
Limit of Detection
Rivers / chemistry*
Solid Phase Extraction / methods
Tandem Mass Spectrometry / methods
Water Pollutants, Chemical / chemistry

Substances

Illicit Drugs
Water Pollutants, Chemical