Quantification of paraquat in postmortem samples by gas chromatography–ion trap mass spectrometry and review of the literature

Moreira, Pedro Costa; Pinho, Paula Guedes de; Baltazar, Maria Teresa; Bastos, Maria de Lourdes; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge

doi:10.1002/bmc.1663

Cited by 38 publications

(30 citation statements)

References 65 publications

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“…Analytical method validation is a mandatory step to evaluate the ability of developed methods to provide accurate results for their routine application. The validation of the method was performed according to European Medicines Agency () and other studies (Gouveia et al ., ; Moreira et al ., ). The European Medicines Agency guidelines relies on the US Food and Drug Administration guidance (US Department of Health and Human Services et al ., ), which is now almost generally accepted by the biopharmaceutical industries as the gold standard method validation approach (Smith, ).…”

Section: Methodsmentioning

confidence: 97%

Simultaneous quantification of tramadol and O‐desmethyltramadol in hair samples by gas chromatography–electron impact/mass spectrometry

Pinho

Oliveira

Costa

et al. 2013

Biomedical Chromatography

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Over recent years, hair has become the ideal matrix for retrospective investigation of chronic abuse, including for tramadol. However, in order to exclude the possibility of external contamination, it is also important to quantify simultaneously its main metabolite, O-desmethyltramadol (M1), which presence in hair reflects systemic exposure. In the present study a methodology aimed at the simultaneous quantification of tramadol and M1 in human hair was developed and validated for the first time. After decontamination of hair samples (60 mg), tramadol and M1 were extracted with methanol in an ultrasonic bath (~5 h). Purification was performed by solid-phase extraction using mixed-mode extraction cartridges. Subsequently to derivatization, analysis was performed by gas chromatography-electron impact/mass spectrometry (GC-EI/MS). The method proved to be selective. The regression analysis for both analytes was shown to be linear in the range of 0.1-20.0 ng/mg with correlation coefficients of 0.9995 and 0.9997 for tramadol and M1, respectively. The coefficients of variation oscillated between 3.85 and 13.24%. The limits of detection were 0.03 and 0.02 ng/mg, and the lower limits of quantification were 0.08 and 0.06 ng/mg for tramadol and M1, respectively. The proof of applicability was performed in hair samples from six patients undergoing tramadol therapy. All samples were positive for tramadol and M1.

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Section: Methodsmentioning

confidence: 97%

Simultaneous quantification of tramadol and O‐desmethyltramadol in hair samples by gas chromatography–electron impact/mass spectrometry

Pinho

Oliveira

Costa

et al. 2013

Biomedical Chromatography

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“…The carrier gas was helium C‐60 at a constant flow‐rate of 1 ml min –1 . All conditions were set as described previously (Moreira et al ., ). Results are presented in nmol PQ per mg of protein.…”

Section: Methodsmentioning

confidence: 97%

RBE4 cells are highly resistant to paraquat‐induced cytotoxicity: studies on uptake and efflux mechanisms

Vilas-Boas

Silva

Pinho

et al. 2013

J of Applied Toxicology

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Paraquat (PQ) is a widely used, highly toxic and non-selective contact herbicide, which has been associated with central neurotoxic effects, namely the development of Parkinson's disease, but whose effects to the blood-brain barrier (BBB) itself have rarely been studied. This work studied the mechanisms of PQ uptake and efflux in a rat's BBB cell model, the RBE4 cells. PQ is believed to enter cells using the basic or neutral amino acid or polyamine transport systems or through the choline-uptake system. In contrast, PQ efflux from cells is reported to be mediated by P-glycoprotein. Therefore, we evaluated PQ-induced cytotoxicity and the effect of some substrates/blockers of these transporters (such as arginine, L-valine, putrescine, hemicholinium-3 and GF120918) on such cytotoxicity. RBE4 cells were shown to be extremely resistant to PQ after 24 h of exposure; even at concentrations as high as 50 mM approximately 45% of the cells remained viable. Prolonging exposure until 48 h elicited significant cytotoxicity only for PQ concentrations above 5 mM. Although hemicholinium-3, a choline-uptake system inhibitor, significantly protected cells against PQ-induced toxicity, none of the effects were observed for arginine, L-valine or putrescine. Meanwhile, inhibiting the efflux pump P-glycoprotein using GF120918 significantly enhanced PQ-induced cytotoxicity. In conclusion, PQ used the choline-uptake system, instead of the transporters for the basic or neutral amino acids or for the polyamines, to enter RBE4 cells. P-glycoprotein extrudes PQ back to the extracellular medium. However, this efflux mechanism only partially explains the observed RBE4 resistance to PQ.

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“…To date, various studies about PQ poisoning have been conducted. Some studies have evaluated the detection and toxicokinetics of PQ in humans, [4][5][6][7][8] while others have evaluated the effects of the treatment such as early hemoperfusion in PQ poisoned patients. [9][10][11] The study on toxic mechanism revealed that PQ is concentrated inside the cells of multiple organs where it undergoes redox cycling.…”

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confidence: 99%

Metabolic Changes in Paraquat Poisoned Patients and Support Vector Machine Model of Discrimination

Wang

Zhang

et al. 2015

Biological & Pharmaceutical Bulletin

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Numerous people die of paraquat (PQ) poisoning every year in the world. Although several studies regarding paraquat (PQ) poisoning have been conducted, the metabolic changes in plasma remain unknown. In this study, the metabolomics of 15 PQ poisoned patients with plasma PQ concentrations in excess of 0.1 µg/ mL and 16 healthy volunteers were investigated. The plasma samples were evaluated through the use of gas chromatography-mass spectrometry (GC/MS) and analyzed by partial least-squares discriminant analysis (PLS-DA). Based on the metabolomics data, a support vector machine (SVM) discrimination model was developed. The results showed the plasma levels of urea, glucose oxime and L-phenylalanine decreased and cholesterol increased in PQ poisoned patients in comparison to healthy volunteers. The SVM discrimination model was developed, and performed with a high degree of accuracy, to distinguish PQ poisoned patients from healthy volunteers. In conclusion, metabolic pathways including the urea cycle, and amino acid, glucose, and cholesterol metabolism were impaired after PQ poisoning. An SVM discrimination model, based on metabolomics data, was established and may become a new powerful tool for the diagnosis of PQ poisoning.

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Quantification of paraquat in postmortem samples by gas chromatography–ion trap mass spectrometry and review of the literature

Cited by 38 publications

References 65 publications

Simultaneous quantification of tramadol and O‐desmethyltramadol in hair samples by gas chromatography–electron impact/mass spectrometry

Simultaneous quantification of tramadol and O‐desmethyltramadol in hair samples by gas chromatography–electron impact/mass spectrometry

RBE4 cells are highly resistant to paraquat‐induced cytotoxicity: studies on uptake and efflux mechanisms

Metabolic Changes in Paraquat Poisoned Patients and Support Vector Machine Model of Discrimination

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