Simple chromatography method for simultaneous determination of dextromethorphan and its main metabolites in human plasma with fluorimetric detection

Afshar, Minoo; Rouini, Mohammad-Reza; Amini, Mohsen

doi:10.1016/j.jchromb.2003.12.009

Cited by 36 publications

(16 citation statements)

References 23 publications

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“…7,9) For the O-demethylation of 3-methoxymorphinan to 3-hydroxymorphinan, CYP2D6 is involved. Finally, dextrorphan and 3-hydroxymorphinan are glucuronidated to give detrorphan glucuronide and 3-hydroxymorphinan glucuronide, which are eliminated by urine.…”

Section: Discussionmentioning

confidence: 99%

“…8) In humans, dextromethorphan is reduced rapidly after oral absorption to dextrorphan (O-demethyl-dextromethorphan) by the polymorphic CYP2D6. 9) Dextromethorphan is also a widely used probe drug for the activity of CYP 2D6 in vivo as well as in vitro. 10) In this study, Cunninghamella blakesleeana AS 3.153 transforming dextromethorphan to dextrorphan is investigated and the optimal transformation system is screened by orthogonal design.…”

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confidence: 99%

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Microbial Transformation of Dextromethorphan by Cunninghamella blakesleeana AS 3.153

et al. 2007

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The capability of Cunninghamella blakesleeana AS 3.153 to transform CYP2D6 probe drug dextromethorphan was investigated. Metabolites produced by strain AS 3.153 were detected by liquid chromatography-tandem mass spectrometry (LC-MS n ) and the metabolite dextrorphan was identified by reference to confirm its structure. The yield of dextrorphan produced by C. blakesleeana AS 3.153 was over 90%. Quinidine, a CYP2D6 selective inhibitor, was applied to investigate its effect on biotransformation. The concentration of quinidine was 4-folds higher than that of dextromethorphan and the yield of dextrorphan was reduced by 84%, which proved there was drug metabolism enzyme similar to CYP2D6 in C. blakesleeana AS 3.153. It is concluded that C. blakesleeana AS 3.153 can be used as the suitable model strain in vitro to mimic human CYP2D6 metabolism.

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Section: Discussionmentioning

confidence: 99%

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Microbial Transformation of Dextromethorphan by Cunninghamella blakesleeana AS 3.153

et al. 2007

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“…Various analytical methods for the determination of dextromethorphan and/or its metabolites in biological matrices have been reported, such as high-performance liquid chromatography combined with fluorescence detection (East and Dye, 1985;Johansson and Svensson, 1988;Chen et al, 1990;Lam and Rodriquez, 1993;Hartter et al, 1996;Bartoletti et al, 1996;Kimiskidis et al, 1996;Bendriss et al, 2001;Hendrickson et al, 2003;Afhsar et al, 2004;Lin et al, 2007) or ultraviolet detection (Park et al, 1984;Vielnascher et al, 1996), capillary electrophoresis (Kristensen, 1998), gas chromatography coupled with different detectors (Pfaff et al, 1983;Bauman and Jonzier-Perey 1988;Wu et al, 2003;Bagheri et al, 2005;Rodriques et al, 2008) and liquid chromatography-mass spectrometry (Vengurlekar et al, 2002;Arellano et al, 2005;Constanzer et al, 2005). GC/MS in the SIM mode and LC-MS/MS are the preferred methods in terms of sensitivity and selectivity.…”

Section: Introductionmentioning

confidence: 99%

A validated SIM GC/MS method for the simultaneous determination of dextromethorphan and its metabolites dextrorphan, 3‐methoxymorphinan and 3‐hydroxymorphinan in biological matrices and its application to in vitro CYP2D6 and CYP3A4 inhibition study

Spanakis

Vizirianakis

Mironidou-Tzouveleki

et al. 2009

Biomedical Chromatography

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Dextromethorphan is used as a probe drug for assessing CYP2D6 and CYP3A4 activity in vivo and in vitro. A SIM GC/MS method without derivatization for the simultaneous determination of dextromethorphan and its metabolites, dextrorphan, 3-methoxymorphinan and 3-hydroxymorphinan, in human plasma, urine and in vitro incubation matrix was developed and validated. Calibration curves indicated good linearity with a coefficient of variation (r) better than 0.995. The lower limit of quantitation was found to be 10 ng/mL for all analytes in all matrices. Intra-day and inter-day precision for dextromethorphan and its metabolites was better than 9.02 and 9.91%, respectively and accuracy ranged between 91.76 and 106.27%. Recovery for dextromethorphan, its metabolites and internal standard levallorphan was greater than 72.68%. The method has been successfully applied for the in vitro inhibition of metabolism of dextromethorphan by CYP2D6 and CYP3A4 using known inhibitors of CYPs such as quinidine and verapamil.

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“…Most of those analytical methods imply chromatographic techniques, such as high-performance liquid chromatography, [5][6][7][8] high-performance liquid chromatography-mass spectrometrymass spectrometry, 9,10 gas chromatography, 11,12 gas chromatography-mass spectrometry 13,14 and high-performance thin-layer chromatography. 15 Capillary electrophoresis 16,17 and multiwavelength and derivative spectrophotometry 18,19 have also been reported for the determinations of DXM.…”

Section: Introductionmentioning

confidence: 99%

Polymeric Membrane Sensors for the Selective Determination of Dextromethorphan in Pharmaceutical Preparations

El-Naby

2008

ANAL. SCI.

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The construction and electrochemical response characteristics of poly(vinyl chloride) matrix ion-selective electrodes (ISEs) for dextromethorphan (DXM) hydrobromide are described. The membranes incorporate ion-association complexes of DXM with reineckate salt {[Cr(NH3)2(SCN)4]NH4} or phosphomolybdic acid [H3(PMo12O40)], as electroactive materials and dioctylphthalate or dibutylsebacate as a plasticizing solvent mediator. The sensors display a fast, stable and linear response with slopes of 54.4 to 59.5 mV/decade at pH 2.5 -6.5 and a detection limit of 1.0 ¥ 10 -6 M. Moreover, the sensors exhibit very good selectivity for DXM over opiate alkaloids, as well as organic and inorganic cations. The sensors proved to be useful for the determination of 5.0 ¥ 10 -5 -1.0 ¥ 10 -3 M DXM hydrobromide in pure as well as in dosage forms by direct potentiometry and standard addition methods. Determination of 5.0 ¥ 10 -4 M DXM using the standard addition method and a sensor based on phosphomolybdate and dioctylphthalate shows an average recovery of 99.8% and a relative standard deviation (RSD) of 0.4%.

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Simple chromatography method for simultaneous determination of dextromethorphan and its main metabolites in human plasma with fluorimetric detection

Cited by 36 publications

References 23 publications

Microbial Transformation of Dextromethorphan by Cunninghamella blakesleeana AS 3.153

Microbial Transformation of Dextromethorphan by Cunninghamella blakesleeana AS 3.153

A validated SIM GC/MS method for the simultaneous determination of dextromethorphan and its metabolites dextrorphan, 3‐methoxymorphinan and 3‐hydroxymorphinan in biological matrices and its application to in vitro CYP2D6 and CYP3A4 inhibition study

Polymeric Membrane Sensors for the Selective Determination of Dextromethorphan in Pharmaceutical Preparations

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