Simultaneous quantification of dextromethorphan and its metabolites dextrorphan, 3-methoxymorphinan and 3-hydroxymorphinan in human plasma by ultra performance liquid chromatography/tandem triple-quadrupole mass spectrometry

Loos, Walter J.; Graan, Anne-Joy M. de; Bruijn, Peter de; Schaik, Ron H.N. van; Fessem, M A C van; Lam, Mei-Ho; Mathijssen, Ron H.J.; Wiemer, Erik A.C.

doi:10.1016/j.jpba.2010.08.033

Cited by 11 publications

(7 citation statements)

References 30 publications

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“…The concentrations of the following drugs and their metabolites were measured by LC-MS in plasma: caffeine and paraxanthine, chlorzoxazone and 6-hydroxychlorzoxazone, omeprazole and 5hydroxyomeprazole, omeprazole sulfone, and urinary dextromethorphan and dextrorphan. Parent drugs and metabolites were analysed as previously described (Frye, Matzke, Adedoyin, Porter, & Branch, 1997;Gonzalez et al, 2002;Loos et al, 2011;Nolin, Gastonguay, Bies, Matzke, & Frye, 2003;Oh, Park, Shinde, Shin, & Kim, 2012). Calibrated standard curves were generated for each parent compound or metabolite to derive sample concentrations.…”

Section: Analytical Techniquesmentioning

confidence: 99%

Altered cytochrome 2E1 and 3A P450‐dependent drug metabolism in advanced ovarian cancer correlates to tumour‐associated inflammation

Trousil

Lee

Edwards

et al. 2019

British J Pharmacology

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Background and Purpose Previous work has focussed on changes in drug metabolism caused by altered activity of CYP3A in the presence of inflammation and, in particular, inflammation associated with malignancy. However, drug metabolism involves a number of other P450s, and therefore, we assessed the effect of cancer‐related inflammation on multiple CYP enzymes using a validated drug cocktail. Experimental Approach Patients with advanced stage ovarian cancer and healthy volunteers were recruited. Participants received caffeine, chlorzoxazone, dextromethorphan, and omeprazole as in vivo probes for CYP1A2, CYP2E1, CYP2D6, CYP3A, and CYP2C19. Blood was collected for serum C‐reactive protein and cytokine analysis. Key Results CYP2E1 activity was markedly up‐regulated in cancer (6‐hydroxychlorzoxazone/chlorzoxazone ratio of 1.30 vs. 2.75), while CYP3A phenotypic activity was repressed in cancer (omeprazole sulfone/omeprazole ratio of 0.23 vs. 0.49). Increased activity of CYP2E1 was associated with raised serum levels of IL‐6, IL‐8, and TNF‐α. Repression of CYP3A correlated with raised levels of serum C‐reactive protein, IL‐6, IL‐8, and TNF‐α. Conclusions and Implications CYP enzyme activity is differentially affected by the presence of tumour‐associated inflammation, affecting particularly CYP2E1‐ and CYP3A‐mediated drug metabolism, and may have profound implications for drug development and prescribing in oncological settings.

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Section: Analytical Techniquesmentioning

confidence: 99%

Altered cytochrome 2E1 and 3A P450‐dependent drug metabolism in advanced ovarian cancer correlates to tumour‐associated inflammation

Trousil

Lee

Edwards

et al. 2019

British J Pharmacology

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“…The organic phase was removed and evaporated under nitrogen stream at 70 °C. Further information of the validated method has been previously described 70 .…”

Section: Measurements Of Membrane Potentials In Beta Cells Of Pancreamentioning

confidence: 99%

Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment

Marquard

Otter

Welters

et al. 2015

Nat Med

142

192

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In the nervous system, NMDA receptors (NMDARs) participate in neurotransmission and modulate the viability of neurons. In contrast, little is known about the role of NMDARs in pancreatic islets and the insulin-secreting beta cells whose functional impairment contributes to diabetes mellitus. Here we found that inhibition of NMDARs in mouse and human islets enhanced their glucose-stimulated insulin secretion (GSIS) and survival of islet cells. Further, NMDAR inhibition prolonged the amount of time that glucose-stimulated beta cells spent in a depolarized state with high cytosolic Ca(2+) concentrations. We also noticed that, in vivo, the NMDAR antagonist dextromethorphan (DXM) enhanced glucose tolerance in mice, and that in vitro dextrorphan, the main metabolite of DXM, amplified the stimulatory effect of exendin-4 on GSIS. In a mouse model of type 2 diabetes mellitus (T2DM), long-term treatment with DXM improved islet insulin content, islet cell mass and blood glucose control. Further, in a small clinical trial we found that individuals with T2DM treated with DXM showed enhanced serum insulin concentrations and glucose tolerance. Our data highlight the possibility that antagonists of NMDARs may provide a useful adjunct treatment for diabetes.

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“…The analytical method employed in this study is one of the few methods that can detect DMP and its metabolite DP. Besides, the sample preparation procedures described in some previous methods generally suffered from low analyte recoveries [15,20] and in most cases, the selectivity of these methods in the presence of a number of other metabolites of DMP was not clearly established.…”

Section: Discussionmentioning

confidence: 99%

Sensitive and Selective Reversed-Phase High Performance Liquid Chromatographic-UV Spectrophotometric Determination of Dextromethorphan and its CYP2D6 Mediated Metabolite, Dextrorphan in Human Urine

Ebeshi¹,

Obodozie²,

Bolaji³

2014

Trop. J. Pharm Res

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Simultaneous quantification of dextromethorphan and its metabolites dextrorphan, 3-methoxymorphinan and 3-hydroxymorphinan in human plasma by ultra performance liquid chromatography/tandem triple-quadrupole mass spectrometry

Cited by 11 publications

References 30 publications

Altered cytochrome 2E1 and 3A P450‐dependent drug metabolism in advanced ovarian cancer correlates to tumour‐associated inflammation

Altered cytochrome 2E1 and 3A P450‐dependent drug metabolism in advanced ovarian cancer correlates to tumour‐associated inflammation

Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment

Sensitive and Selective Reversed-Phase High Performance Liquid Chromatographic-UV Spectrophotometric Determination of Dextromethorphan and its CYP2D6 Mediated Metabolite, Dextrorphan in Human Urine

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