Determination of antipsychotic drugs in hospital and wastewater treatment plant samples by gas chromatography/tandem mass spectrometry

Logarinho, F.; Rosado, Tiago; Lourenço, Caroline Caramano de; Barroso, Mário; Araújo, André R. T. S.; Gallardo, Eugénia

doi:10.1016/j.jchromb.2016.10.031

Cited by 21 publications

(7 citation statements)

References 38 publications

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“…We acknowledge that MS/MS detection in combination with LC is now dominating the analytical field, and the determination of antipsychotic drugs is no exception . Our research group has successfully applied GC combined with MS/MS to determine these same analytes in hospital wastewaters and plasma samples using SPE and MEPS as clean‐up procedure, respectively. The literature does not highlight very much the application of GC for this purpose, an analytical technique which is accessible in most therapeutic monitoring laboratories giving results as accurate and reliable as those obtained with LC/MS/MS.…”

Section: Resultsmentioning

confidence: 99%

Development and validation of a gas chromatography/tandem mass spectrometry method for simultaneous quantitation of several antipsychotics in human plasma and oral fluid

Rosado

Oppolzer

Cruz

et al. 2018

Rapid Comm Mass Spectrometry

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The described method was proven selective and sensitive for the determination of antipsychotics in low sample volumes using SPE and GC/MS/MS. This method was considered suitable not only for routine analysis of patients undergoing antipsychotic treatment (to evaluate compliance), but also in forensic scenarios where the studied compounds may be involved. To the best of our knowledge, this is the first work that reports the determination of antipsychotic drugs in oral fluid using MS/MS.

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Section: Resultsmentioning

confidence: 99%

Development and validation of a gas chromatography/tandem mass spectrometry method for simultaneous quantitation of several antipsychotics in human plasma and oral fluid

Rosado

Oppolzer

Cruz

et al. 2018

Rapid Comm Mass Spectrometry

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“…* p < 0:05, ** p < 0:01, *** p < 0:001 as determined by post hoc Dunnett's test following one-way analysis of variance (ANOVA). sources as a consequence of improper medical waste disposal (Logarinho et al 2016;Silveira et al 2013;Van De Steene et al 2010).…”

Section: Environmental Health Perspectivesmentioning

confidence: 99%

Screening ToxCast™ for Chemicals That Affect Cholesterol Biosynthesis: Studies in Cell Culture and Human Induced Pluripotent Stem Cell–Derived Neuroprogenitors

Wages

Joshi

Tallman

et al. 2020

Environ Health Perspect

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BACKGROUND: Changes in cholesterol metabolism are common hallmarks of neurodevelopmental pathologies. A diverse array of genetic disorders of cholesterol metabolism support this claim as do multiple lines of research that demonstrate chemical inhibition of cholesterol biosynthesis compromises neurodevelopment. Recent work has revealed that a number of commonly used pharmaceuticals induce changes in cholesterol metabolism that are similar to changes induced by genetic disorders with devastating neurodevelopmental deficiencies. OBJECTIVES: We tested the hypothesis that common environmental toxicants may also impair cholesterol metabolism and thereby possibly contribute to neurodevelopmental toxicity. METHODS: Using high-throughput screening with a targeted lipidomic analysis and the mouse neuroblastoma cell line, Neuro-2a, the ToxCast™ chemical library was screened for compounds that impact sterol metabolism. Validation of chemical effects was conducted by assessing cholesterol biosynthesis in human induced pluripotent stem cell (hiPSC)-derived neuroprogenitors using an isotopically labeled cholesterol precursor and by monitoring product formation with UPLC-MS/MS. RESULTS: Twenty-nine compounds were identified as validated lead-hits, and four were prioritized for further study (endosulfan sulfate, tributyltin chloride, fenpropimorph, and spiroxamine). All four compounds were validated to cause hypocholesterolemia in Neuro-2a cells. The morpholine-like fungicides, fenpropimorph and spiroxamine, mirrored their Neuro-2a activity in four immortalized human cell lines and in a human neuroprogenitor model derived from hiPSCs, but endosulfan sulfate and tributyltin chloride did not. CONCLUSIONS: These data reveal the existence of environmental compounds that interrupt cholesterol biosynthesis and that methodologically hiPSC neuroprogenitor cells provide a particularly sensitive system to monitor the effect of small molecules on de novo cholesterol formation.

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“…In recent years, AAPs have been widely prescribed to more vulnerable populations, such as in children, elderly, and pregnant women, in many cases for 'off-label' indications such as attention-deficit/hyperactivity disorders and disruptive behavior disorders (5,(7)(8)(9). This expansion of use has correlated with an increase in environmental detection of AAP drugs in municipal wastewater, hospital sewage, and drinking water (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

The Atypical Antipsychotic Quetiapine Induces Multiple Antibiotic Resistance in Escherichia coli

Kyono

Ellezian

et al. 2021

Preprint

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Atypical antipsychotic (AAP) medication is a critical tool for treating symptoms of psychiatric disorders. While AAPs primarily target dopamine (D2) and serotonin (5HT2A and 5HT1A) receptors, they also exhibit intrinsic antimicrobial activity as an off-target effect. Because AAPs are often prescribed to patients for many years, a potential risk associated with long-term AAP use is the unintended emergence of bacteria with antimicrobial resistance (AMR). Here, we show that exposure to the AAP quetiapine at estimated gut concentrations promotes AMR in Escherichia coli after six weeks. Quetiapine-exposed isolates exhibited an increase in minimal inhibitory concentrations (MICs) for ampicillin, tetracycline, ceftriaxone, and levofloxacin. By whole genome sequencing analysis, we identified mutations in genes that confer AMR, including the repressor for the multiple antibiotic resistance mar operon (marR), and real-time RT-qPCR analysis showed increased levels of marA, acrA, and tolC mRNAs and a reduced level of ompF mRNA in the isolates carrying marR mutations. To determine the contribution of each marR mutation to AMR, we constructed isogenic strains carrying individual mutant marR alleles in the parent background and re-evaluated their resistant phenotypes using MIC and RT-qPCR assays. While marR mutations induced a robust activity of the mar operon, they resulted in only a modest increase in MICs. Interestingly, although these marR mutations did not fully recapitulate the AMR phenotype of the quetiapine-exposed isolates, we show that marR mutations promote growth fitness in the presence of quetiapine. Our findings revealed an important link between the use of AAPs and AMR development in E. coli.

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Determination of antipsychotic drugs in hospital and wastewater treatment plant samples by gas chromatography/tandem mass spectrometry

Cited by 21 publications

References 38 publications

Development and validation of a gas chromatography/tandem mass spectrometry method for simultaneous quantitation of several antipsychotics in human plasma and oral fluid

Development and validation of a gas chromatography/tandem mass spectrometry method for simultaneous quantitation of several antipsychotics in human plasma and oral fluid

Screening ToxCast™ for Chemicals That Affect Cholesterol Biosynthesis: Studies in Cell Culture and Human Induced Pluripotent Stem Cell–Derived Neuroprogenitors

The Atypical Antipsychotic Quetiapine Induces Multiple Antibiotic Resistance in Escherichia coli

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