Stereoselective high-performance liquid chromatographic determination of ketoprofen, ibuprofen and fenoprofen in plasma using a chiral α1-acid glycoprotein column

Menzel-Soglowek, S.; Geißlinger, Gerd; Brune, Kay

doi:10.1016/s0378-4347(00)83780-9

Cited by 87 publications

(32 citation statements)

References 24 publications

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“…Protein synthesis was induced by the addition of 1 mM IPTG. The 2-arylpropionyl-CoA epimerase activity of the recombinant protein was determined in the enzyme fractions by incubation of the chemically synthesized (Ϫ)-(R)-IBU-CoA thioesters and subsequent stereoselective high pressure liquid chromatography analysis of IBU after alkaline hydrolysis as described previously (20,13).…”

Section: Methodsmentioning

confidence: 99%

Molecular Cloning and Expression of a 2-Arylpropionyl-Coenzyme A Epimerase: A Key Enzyme in the Inversion Metabolism of Ibuprofen

et al. 1997

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SUMMARYThe 2-arylpropionic acid derivatives, including ibuprofen, are the most widely used anti-inflammatory analgesic cyclooxygenase inhibitors. The (Ϫ)-R-enantiomer, which is inactive in terms of cyclooxygenase inhibition, is epimerized in vivo via the 2-arylpropionyl-coenzyme A (CoA) epimerase to the cyclooxygenase-inhibiting (ϩ)-S-enantiomer. The molecular biology of the epimerization pathway is largely unknown. To clarify this mechanism, the sequence of the 2-arylpropionyl-CoA epimerase was identified, and the enzyme cloned and expressed. A cDNA clone encoding the 2-arylpropionyl-CoA epimerase was isolated from a rat liver cDNA library. The nucleotide and the deduced amino acid sequence of this enzyme was determined. Significant amino acid sequence similarity was found between the rat epimerase and carnitine dehydratases from Caenorhabditis elegans (41%) and Escherichia coli (27%). A bacterial expression system (E. coli strain M15[pREP4]) was used to express the epimerase protein, representing up to 20 -30% of the total cellular E. coli protein. The expression of the epimerase was confirmed with Western blots using specific antiepimerase antibodies and by measuring the rate of inversion of (R)-ibuprofenoyl-CoA. Northern blot analysis revealed a prominent 1.9-kb mRNA transcript in different rat tissues. In addition to its obvious importance in drug metabolism, the homology of the epimerase with carnitine dehydratases from several species suggests that this protein, which up to now has only been characterized as having a role in drug transformation, has a function in lipid metabolism.

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Section: Methodsmentioning

confidence: 99%

Molecular Cloning and Expression of a 2-Arylpropionyl-Coenzyme A Epimerase: A Key Enzyme in the Inversion Metabolism of Ibuprofen

et al. 1997

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“…ibuprofen were determined by HPLC with UV detection at 220 nm (22,26). Briefly, R-(Ϫ)-and S-(ϩ)-ibuprofen and the internal standard, fenoprofen, were extracted from plasma with ethyl acetate.…”

Section: Bioanalysis Of Ibuprofen the Plasma Concentrations Of R-(ϫ)mentioning

confidence: 99%

Effects of the Antifungals Voriconazole and Fluconazole on the Pharmacokinetics of S -(+)- and R -(−)-Ibuprofen

Hynninen

Olkkola

Leino

et al. 2006

Antimicrob Agents Chemother

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Our objective was to study the effects of the antifungals voriconazole and fluconazole on the pharmacokinetics of S-(؉)-and R-(؊)-ibuprofen. Twelve healthy male volunteers took a single oral dose of 400 mg racemic ibuprofen in a randomized order either alone, after ingestion of voriconazole at 400 mg twice daily on the first day and 200 mg twice daily on the second day, or after ingestion of fluconazole at 400 mg on the first day and 200 mg on the second day. Ibuprofen was ingested 1 h after administration of the last dose of voriconazole or fluconazole. Plasma concentrations of S-(؉)-and R-(؊)-ibuprofen were measured for up to 24 h. In the voriconazole phase, the mean area under the plasma concentration-time curve (AUC) of S-(؉)-ibuprofen was 205% (P < 0.001) of the respective control value and the mean peak plasma concentration (C max ) was 122% (P < 0.01) of the respective control value. The mean elimination half-life (t 1/2 ) was prolonged from 2.4 to 3.2 h (P < 0.01) by voriconazole. In the fluconazole phase, the mean AUC of S-(؉)-ibuprofen was 183% of the control value (P < 0.001) and its mean C max was 116% of the control value (P < 0. Voriconazole is a novel triazole antifungal agent, available as oral and intravenous formulations, with potent activity against a broad spectrum of clinically significant pathogens, including Aspergillus, Cryptococcus, and Candida species (5,8,27). Voriconazole is metabolized by the cytochrome P450 (CYP) enzyme system, mainly by the polymorphic enzyme CYP2C19 and to a lesser extent by the polymorphic enzymes CYP2C9 and CYP3A4 (13; G. Mikus, M. Drzevinska, V. Schoevel, J. Burhenne, K. D. Riedel, T. Thomsen, M. M. Hoffmann, J. Weis, J. Rengelshausen, and W. E. Haefeli, Abstr. 7th Congr. Eur. Assoc. Clin. Pharmacol. Ther., abstr. 418, 2005). In vivo studies have shown that addition of voriconazole at 300 mg twice daily to a 30-mg oral dose of warfarin in healthy volunteers resulted in a doubling of the prothrombin time from 8.4 to 16.6 s (28), probably due to inhibition of CYP2C9. In addition, coadministration of voriconazole has significantly increased the area under the plasma concentration-time curve (AUC) of phenytoin, a substrate of CYP2C9 (30); the AUC of omeprazole, a substrate of CYP2C19 (http://www.emea.eu .int./humandocs/Humans/EPAR/vfend/vfend.htm); and the AUC of cyclosporine, which is metabolized by CYP3A4 (31).Fluconazole is another azole antifungal agent and a welldocumented potent inhibitor of CYP2C9-catalyzed reactions both in vitro (3,20) and in vivo (4, 18) and a weaker inhibitor of CYP3A4-catalyzed reactions (23). It has also been found to inhibit CYP2C19-catalyzed reactions both in vitro (34) and in vivo (17). However, there are few data on the possible interactions between fluconazole and nonsteroidal anti-inflammatory drugs (NSAIDs). Treatment with fluconazole significantly increased the AUC of the CYP2C9 substrate celecoxib (7), and recently, it has been shown that coadministration of fluconazole and a novel cyclooxygenase 2 (COX-2)-selective inhibitor,...

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“…In the direct HPLC methods, a chiral stationary phase is used and the enantiomers are analyzed without sample derivatization. Certain direct HPLC methods employ ultra-violet (UV) detection using α 1 -acid glycoprotein [16][17][18][19], β-cyclodextrin [20], cellulose [21], polysaccharide [22], and amylose derivative [23] chiral sta-tionary phases (CSPs). A cellulose derivative CSP using radiometric and tandem mass spectrometric (MS/MS) detection [24] and an amylose derivative CSP using MS/MS [25] were also employed for the determination of ibuprofen enantiomers.…”

Section: Introductionmentioning

confidence: 99%

“…The direct HPLC methods have the advantage that the ibuprofen enantiomers can be analyzed without derivatization, however, these assays have poor sensitivity, reproducibility, require a large sample volume [16,[18][19][20] or lack the satisfactory chromatographic baseline separation of the stereoisomer peaks [20,25]. Some direct HPLC methods achieved good sensitivity and use a small sample volume, but due to the non-selective characteristics of the UV detection they require extended analysis time to avoid interferences between the ibuprofen enantiomers and the co-eluting endogenous components from the biological matrix [23].…”

Section: Introductionmentioning

confidence: 99%

A Validated Enantioselective Assay for the Determination of Ibuprofen in Human Plasma Using Ultra Performance Liquid Chromatography with Tandem Mass Spectrometry (UPLC-MS/MS)

Szeitz¹,

Edginton²,

Peng³

et al. 2010

AJAC

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A modified ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitation of ibuprofen enantiomers in human plasma. Ibuprofen and flurbiprofen (internal standard) were extracted from human plasma at acidic pH, using a single-step liquid-liquid extraction with methyl-tert-butyl ether. The enantiomers of ibuprofen and flurbiprofen were derivatized to yield the corresponding diastereomers. Chromatographic separation was achieved using a phenyl column with a run time of 20 min. (R)-and (S)-ibuprofen were quantitated at the multiple reaction monitoring (MRM) transition of m/z 360.2  232.1, and (R)-and (S)-flurbiprofen were monitored at the MRM transition of m/z 398.3  270.1. The method was validated for accuracy, precision, linearity, range, limit of quantitation (LOQ), limit of detection (LOD), selectivity, absolute recovery, matrix effect, dilution integrity, and evaluation of carry-over. Accuracy for (R)-ibuprofen ranged between -11.8% and 11.2%, and for (S)-ibuprofen between -8.6% and -0.3%. Precision for (R)-ibuprofen was ≤ 11.2%, and for (S)-ibuprofen ≤ 7.0%. The calibration curves were weighted (1/X 2 , n = 7) and were linear with r 2 for (R)-ibuprofen ≥ 0.988 and for (S)-ibuprofen ≥ 0.990. The range of the method was 50 to 5000 ng/mL with the LOQ of 50 ng/mL, and LOD of 1 ng/mL, for (R)-and (S)-ibuprofen requiring 100 µL of sample. The method was applied successfully to a pharmacokinetic study with the administration of a single oral dose of ibuprofen capsules to human subjects.

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Stereoselective high-performance liquid chromatographic determination of ketoprofen, ibuprofen and fenoprofen in plasma using a chiral α1-acid glycoprotein column

Cited by 87 publications

References 24 publications

Molecular Cloning and Expression of a 2-Arylpropionyl-Coenzyme A Epimerase: A Key Enzyme in the Inversion Metabolism of Ibuprofen

Molecular Cloning and Expression of a 2-Arylpropionyl-Coenzyme A Epimerase: A Key Enzyme in the Inversion Metabolism of Ibuprofen

Effects of the Antifungals Voriconazole and Fluconazole on the Pharmacokinetics of S -(+)- and R -(−)-Ibuprofen

A Validated Enantioselective Assay for the Determination of Ibuprofen in Human Plasma Using Ultra Performance Liquid Chromatography with Tandem Mass Spectrometry (UPLC-MS/MS)

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